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

Sponsor

Novartis (Industry)

Overall Status

Completed

CT.gov ID

NCT00289978

Collaborator

(none)

1,272

Enrollment

115

Locations

Arms

Duration (Months)

11.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study assessed the efficacy, safety, and tolerability of 2 doses of oral fingolimod (1.25 mg/day and 0.5 mg/day) compared to placebo in patients with relapsing-remitting multiple sclerosis (RRMS)

Condition or Disease	Intervention/Treatment	Phase
Relapsing-remitting Multiple Sclerosis	Drug: Fingolimod 1.25 mg Drug: Fingolimod 0.5 mg Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1272 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A 24-month, Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of Fingolimod 1.25 mg and 0.5 mg Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multiple Sclerosis

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Jul 1, 2009

Actual Study Completion Date :

Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fingolimod 1.25 mg	Drug: Fingolimod 1.25 mg Patients self-administered fingolimod 1.25 mg capsules orally once daily.
Experimental: Fingolimod 0.5 mg	Drug: Fingolimod 0.5 mg Patients self-administered fingolimod 0.5 mg capsules orally once daily.
Placebo Comparator: Placebo	Drug: Placebo Patients self-administered a fingolimod placebo capsule orally once daily.

Arm

Intervention/Treatment

Experimental: Fingolimod 1.25 mg

Drug: Fingolimod 1.25 mg

Patients self-administered fingolimod 1.25 mg capsules orally once daily.

Experimental: Fingolimod 0.5 mg

Drug: Fingolimod 0.5 mg

Patients self-administered fingolimod 0.5 mg capsules orally once daily.

Placebo Comparator: Placebo

Drug: Placebo

Patients self-administered a fingolimod placebo capsule orally once daily.

Outcome Measures

Primary Outcome Measures

Estimated Annualized Aggregate Relapse Rate (ARR) [Baseline to end of study (Month 24)]
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.

Secondary Outcome Measures

Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS) [Baseline to end of study (Month 24)]
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.
Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline [Baseline to end of study (Month 24)]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female patients between ages 18-55 with a diagnosis of multiple sclerosis
Patients with a relapsing-remitting disease course
Patients with EDSS score of 0-5.5

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 applied to this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Queen Elizabeth Hospital	Woodville South	South Australia	Australia	5011
2	North Gosford Private Hospital	Burrabil Avenue, Suite 17, Gosford		Australia	NSW 2250
3	Strategic Health Evaluators	Chatswood		Australia	2067
4	St Vincent's Hospital Melbourne, Department of Clinical Neurosciences	Fitzroy		Australia	3065 VIC
5	Austin Health, Department of Neurology	Heidelberg		Australia	3084
6	Algemeen Ziekenhuis St. Jan, Department of Neurology	Ruddershove 10	Brugge	Belgium	8000
7	Erasme Hospital	Route de Lennik 808	Brussels	Belgium	1070
8	CHU Charleroi, Hôpital Civil	Boulevard Paul Janson 92	Charleroi	Belgium	6000
9	University Hospital Gasthuisberg	Department Neurology, Herestraat 49	Leuven	Belgium	3000
10	AZ Alma	Department of Neurology & Rehab-Umit, Gentsesteenweg 132	Sijsele	Belgium	8340
11	Regionaal Ziekenhuis	St.Trudo, Diestersteenweg 100,	St.Truiden	Belgium	3800
12	MS Klinik	Boemerangstraat 2, Overpelt		Belgium	3900
13	National Multiple Sclerose Centrum v.z.w	Vanheylenstraat 16, Melsbroek		Belgium	1820
14	University of British Columbia	ME498 2211 Wesbrook Mall, Vancouver	British Columbia	Canada	V6T 2B5
15	DMSRU - Capital Health	Halifax	Nova Scotia	Canada
16	Kingston General Hospital, MS Clinic	Connell 7, 76 Stuart Street, Kingston	Ontario	Canada	K7L 2V7
17	Nepean Medical Center	Ottawa	Ontario	Canada	K2G 6E2
18	St. Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
19	Clinical Trials Office,	Trillium Health Center, 00 Queesway West, Mississauga	Ontario	Canada	L5B 1B8
20	Hopital Maisonneuve-Rosemont, Recherche Clinique de Neurologie	Montreal	Quebec	Canada	H1T 2M4
21	University of Saskatchewan	Regina	Saskatchewan	Canada	S4T 1A5
22	Military Hospital of Brno	Department of Neurology, Zabrdovicka 3	Brno	Czech Republic	63600
23	Faculty Hospital St. Anne	First Department of Neurology, Pekarska 53	Brno	Czech Republic	65691
24	Faculty Hospital	Department of Neurology, I.P. Paulova 6	Olomouc	Czech Republic	77520
25	Hospital of Pardubice	Department of Neurology, Kyjevska 44	Pardubice	Czech Republic	53203
26	Faculty Hospital	Department of Neurology, Alej Svobody 80	Plzeň	Czech Republic	3046
27	Faculty Hospital Motol, MS Center	Department of Neurology, V Uvalu 84	Prague 5	Czech Republic	15006
28	Vseobecna fakultni nemocnice	MS Centrum, Neurologicka klinika, Karlovo namesti 32	Praha 2	Czech Republic	12808
29	Neurologicka klinika, Fakultni nemocnice	Kralovske Vinohrady, Srobarova 50	Praha	Czech Republic	10034
30	MS Centrum	Neurology Department of Hospital Teplice, Duchcovska 53	Teplice	Czech Republic	41529
31	Centrum neurologicke pece	Jiraskova 1389, Rychnov nad Kneznou		Czech Republic	51601
32	Facultní Nemocnice Spoliklinikou Ostrava, Neurology Department	Ostrava		Czech Republic	70852
33	Helsinki Headache Center Postitalon Lääkäriasema	Mannnerheiminaukio 1 B 2 Floor	Helsinki	Finland	0100
34	Finnish Special Neurology Center Ltd.	Brahenkatu 11 D,	Turku	Finland	20100
35	Suomen Terveystalo/ Päänsärkykeskus, Tampere	Hämeenkatu 18, 6th fl., Tampere		Finland	33200
36	Turku University Hospital, Neurology Department 799	Kiinanmyllynkatu 11- 14, Turku		Finland	20520
37	Hyvinkään sairaala	Neurologian poliklinikka, Sairaalankatu 1, Hyvinkää		Finland	05850
38	CHU La Timone	Service Neurologie, Boulevard Jean Moulin, Marsielle Cedex 5		France	13385
39	Investigational Site	Berlin		Germany	10117
40	Investigational Site	Berlin		Germany	13347
41	Investigational Site	Dusseldorf		Germany	40225
42	Investigational Site	Giessen		Germany	35385
43	Investigational Site	Hamburg		Germany	20099
44	Investigational Site	Hamburg		Germany	20246
45	Investigational Site	Leipzig		Germany	04103
46	Investigational Site	Magdeburg		Germany	39120
47	Investigational Site	Munchen		Germany	80331
48	Investigational Site	Munchen		Germany	81377
49	Investigational Site	Munster		Germany	48149
50	Investigational Site	Regensburg		Germany	93053
51	Investigational Site	Seesen/Harz		Germany	38723
52	Investigational Site	Stuttgart		Germany	70191
53	Investigational Site	Tubingen		Germany	72076
54	Investigational Site	Wurzburg		Germany	97080
55	Athens Naval Hospital, Neurology Department	Athens		Greece	11521
56	Neurology Department Athens General Hospital, G. Gennimatas	Mesogeion 154 Ave., Athens		Greece	11527
57	1st IKA Papadimitriou Neurology Dept	Terma Zaimi, Melissia-Athens		Greece	15127
58	University General Hospital of Thessaloniki "AHEPA", B' University Department of Neurology	Thessaloniki		Greece	54636
59	Barzilai Medical Center	Ashkelon		Israel	78306
60	Carmel Medical Center	Haifa		Israel	34362
61	Sieff Medical Center	Safed		Israel	13100
62	Sheba - Medical Center	Tel Hashomer, Ramat-Gan,		Israel	52621
63	Kaunas University Hospital Department of Neurology	Eiveniu 2, Kaunas		Lithuania	LY-50009
64	Academisch Ziekenhuis VU	De Boelelaan 1118	Amsterdam	Netherlands	1081
65	St. Antonius Ziekenhuis	Postbus 2500	Nieuwegein	Netherlands	3430 EM
66	Multiple Clerosis Center Nijmegen	Heiweg 97	Nyimegen	Netherlands	6533
67	Erasmus MC	Dr. Molewaterplein 40	Rotterdam	Netherlands	3015 GD
68	Sint Elisabeth Ziekenhuis	Hilvarenbeekse Weg 60	Tilburg	Netherlands	5022
69	Maaslandziekenhuis Sittard	Walramstraat 23, BK Sittard		Netherlands	6131
70	Samodzielny Publiczny Szpital Kliniczny	Klinika Neurologii, Ul. Marii Skłodowskiej-Curie 24 A	Bialystok	Poland	15-276
71	Niezalezny Zespol Opieki Zdrowotnej Kendron	Ul. Swietego Mikolaja 1/8	Bialystok	Poland	15-420
72	Oddzial Neurologiczny i Leczenia Udarow	Mozgu, Nowe Ogrody 1/6	Gdańsk	Poland	80-803
73	Katedra i Klinika Neurologii Slaskiej Akademii Medycznej	ul. Medykow 14	Katowice	Poland	40-752
74	Univ. Med. Sci. Poznan, Katedra i Klinika Neurologii,	Department of Neurology, ul. Przybyszewskiego 49	Poznan	Poland	60-355
75	CSK MSWiA Hospital	Department of Neurology, Wołoska 137	Warsaw	Poland	02-507
76	Jadwiga Kruszewska-Ozimska, Instytut Psychiatrii i Neurologii	II Klinika Neurologii, ul. Sobieskiego 1/9	Warsaw	Poland	02-957
77	Centralny Szpital Kliniczny, Klinika Neurologii	MSWiAw Warszawie, Woloska 137	Warszawa	Poland	00-909
78	Katedra i Klinika Neurologii Centralny Szpital Kliniczny AM w Warszawie	ul. Banacha 1A	Warszawa	Poland	01-097
79	Medical University of Lodz	Lodz		Poland
80	Interregional Clinical Diagnistic Center, Neurology Department	Kazan		Russian Federation	420111
81	Central Clinical Hospital of Medical Center of Administration of President of Russian Federation	Moscow		Russian Federation	121356
82	Moscow Regional Research Clinical Institue	Moscow		Russian Federation	129110
83	GUZ "Central Medical Sanitary Department #122 of Federal Medical-Biological agency", Neurology department	St-Petersburg		Russian Federation
84	Military Medical Academy, Neurology Department	St. Petersburg		Russian Federation	194044
85	II. Neurologická klinika Fakultná nemocnica s poliklinikou Bratislava pracovisko Kramáre	Limbová 5	Bratislava	Slovakia	833 05
86	Neurologická klinika, Martinská fakultná nemocnica	Kollárova 2, Martin		Slovakia	03659
87	I. Neurologická klinika, Fakultná nemocnica s poliklinikou Bratislava pracovisko Staré mesto	Mickiewiczova 13, Bratislava		Slovakia	813 69
88	Neurologické oddelenie, Nemocnica s poliklinikou Žilina	ul.V. Spanyola 43, Žilina		Slovakia	012 07
89	Umhlanga Hospital	Umhlanga	KZN	South Africa	4319
90	Division of Neurology, Groote Schuur Hospital	E 8-74, Groote Schuur Hospital, Observatory Cape Town		South Africa	7925
91	Private Neurologist (Morningside Medi-Clinic), Suite C, Block C, Rochester Place	Sandton		South Africa	2196
92	MS Centrum	Forskningsenhet, SU/Östra CKÖ plan 0	Gothenburg	Sweden	41345
93	Karolinska University Hospital Huddinge	Department Of Neurology R54, Stockholm		Sweden	14186
94	Karolinska University Hospital, Department of Medicine	Neuroimmunology unit, CMM L8:04, Stockholm		Sweden	171 76
95	Kantonsspital Basel, Policlinic	Neurology-Neurosurgical, Petersgraben 4	Basel	Switzerland	4031
96	Centre Hospitalier, Universitaire Vaudois Policlinique de Neurologie	Rue du Bugnon	Lausanne	Switzerland	1011
97	UniversitätsSpital Zürich, Neurologische Klinik	Frauenklinikstr. 26, Zurich		Switzerland	8091
98	Hacettepe Universiti Hospitals	Department of Neurology	Ankara	Turkey
99	Gazi University	Medical Faculty Neurology Department	Besevler Ankara	Turkey	06500
100	EGE University	Medical Faculty Hospital Neurolgy Department	Bornova Izmir	Turkey	35100
101	Istanbul University, Istanbul Faculty of Medicine	Departement of Neurology	Capa Istanbul	Turkey	34093
102	Istanbul University, Cerrahpasa School of Medicine	Department of Neurology	Cerrahpasa Istanbul	Turkey	34098
103	Gaziantep University School of Medicine	Neurology Department	Gaziantep	Turkey	27070
104	Uludag University Faculty of Medche	Tip Fakultesi, Noroloji ABD	Görükle / Bursa	Turkey
105	Tepecik Training and Research	Hospital Neurology Service, 35120 Gaziler Cad. Izmir		Turkey
106	Dokuz University Medical Faculty, Neurology Department	Inciralti, Izmir		Turkey	35340
107	Bakirkoy Ruh ve Sinir Hastaliklari Hastanesi	Istanbul		Turkey	34147
108	Mersin Universitesi Tip Fakultesi Hastanesi	Noroloji ABD, Mersin		Turkey	33079
109	T.C. Saglik Bakanligi Goztepe Egitim ve Arastirma Hastanesi	Noroloji Klinigi, Göztepe Istanbul		Turkey	34722
110	King's College Hospital, Trials office Academie Neuroscience Center	P041 Institute of Psychiatry, Denmark Hill	London	United Kingdom	SES 8AF
111	Queens Medical Centre	Division of Clinical Neurology Medical School	Nottingham	United Kingdom	NG7 24H
112	Royal Hallamshire Hospital	Glossop Road	Sheffield	United Kingdom	S102JF
113	St. George's Hospital, Neurology Dept. Atkinson Morley Wing	Backshaw Road, London		United Kingdom	Tooting London SW17 0QT
114	Frenchay Hospital, Department of Neurology	Beckspool Road, Bristol		United Kingdom	BS16 1LE
115	Royal Victoria Infirmary	Queen Victoria Road, Newcastle-upon-Tyne		United Kingdom	NE1 4LP

Sponsors and Collaborators

Novartis

Investigators

Study Chair: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Fingolimod clinical trials information website

Publications

None provided.

Responsible Party:

Novartis

ClinicalTrials.gov Identifier:

NCT00289978

Other Study ID Numbers:

CFTY720D2301

First Posted:

Feb 10, 2006

Last Update Posted:

Apr 11, 2012

Last Verified:

Apr 1, 2012

Keywords provided by Novartis

Multiple Sclerosis

FTY720

Fingolimod

Additional relevant MeSH terms:

Multiple Sclerosis

Multiple Sclerosis, Relapsing-Remitting

Sclerosis

Fingolimod Hydrochloride

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Fingolimod 1.25 mg	Fingolimod 0.5 mg	Placebo
Arm/Group Description	Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Patients self-administered a fingolimod placebo capsule orally once daily.
Period Title: Overall Study
STARTED	429	425	418
COMPLETED	332	369	332
NOT COMPLETED	97	56	86

Baseline Characteristics

Arm/Group Title	Fingolimod 1.25 mg	Fingolimod 0.5 mg	Placebo	Total
Arm/Group Description	Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Patients self-administered a fingolimod placebo capsule orally once daily.	Total of all reporting groups
Overall Participants	429	425	418	1272
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.4 (8.91)	36.6 (8.77)	37.2 (8.60)	37.1 (8.76)
Age, Customized (participants) [Number]
<18 years	1 0.2%	0 0%	0 0%	1 0.1%
18 -30	107 24.9%	120 28.2%	97 23.2%	324 25.5%
31-40	147 34.3%	162 38.1%	165 39.5%	474 37.3%
41-55	174 40.6%	143 33.6%	156 37.3%	473 37.2%
Sex: Female, Male (Count of Participants)
Female	295 68.8%	296 69.6%	298 71.3%	889 69.9%
Male	134 31.2%	129 30.4%	120 28.7%	383 30.1%
Duration of multiple sclerosis since first symptoms (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	8.4 (6.86)	8.0 (6.60)	8.1 (6.35)	8.2 (6.60)
Number of relapses in last 2 years (relapses) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [relapses]	1.5 (0.81)	1.5 (0.76)	1.4 (0.73)	1.5 (0.77)
Expanded Disability Status Scale (EDSS) (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	2.41 (1.36)	2.30 (1.29)	2.49 (1.29)	2.40 (1.32)

Outcome Measures

1. Primary Outcome

Title	Estimated Annualized Aggregate Relapse Rate (ARR)
Description	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.
Time Frame	Baseline to end of study (Month 24)

Outcome Measure Data

Analysis Population Description
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.

Arm/Group Title	Fingolimod 1.25 mg	Fingolimod 0.5 mg	Placebo
Arm/Group Description	Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Patients self-administered a fingolimod placebo capsule orally once daily.
Measure Participants	429	425	418
Number (95% Confidence Interval) [Relapses per year]	0.16	0.18	0.40

2. Secondary Outcome

Title	Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS)
Description	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.
Time Frame	Baseline to end of study (Month 24)

Outcome Measure Data

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

Arm/Group Title	Fingolimod 1.25 mg	Fingolimod 0.5 mg	Placebo
Arm/Group Description	Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Patients self-administered a fingolimod placebo capsule orally once daily.
Measure Participants	429	425	418
Number (95% Confidence Interval) [Percentage of participants]	83.4 (1.87) 19.4%	82.3 (1.89) 19.4%	75.9 (2.17) 18.2%

3. Secondary Outcome

Title	Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline
Description	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.
Time Frame	Baseline to end of study (Month 24)

Outcome Measure Data

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

Arm/Group Title	Fingolimod 1.25 mg	Fingolimod 0.5 mg	Placebo
Arm/Group Description	Patients self-administered fingolimod 1.25 mg capsules orally once daily.	Patients self-administered fingolimod 0.5 mg capsules orally once daily.	Patients self-administered a fingolimod placebo capsule orally once daily.
Measure Participants	429	425	418
Measure patients with non-missing values	337	370	339
Mean (Standard Deviation) [T2 lesions]	2.5 (5.52)	2.5 (7.19)	9.8 (13.17)

Adverse Events

	Fingolimod 1.25 mg		Fingolimod 0.5 mg		Placebo
Time Frame	24 Months
Adverse Event Reporting Description	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.

Arm/Group Title	Fingolimod 1.25 mg		Fingolimod 0.5 mg		Placebo
Arm/Group Description	Patients self-administered fingolimod 1.25 mg capsules orally once daily.		Patients self-administered fingolimod 0.5 mg capsules orally once daily.		Patients self-administered a fingolimod placebo capsule orally once daily.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Fingolimod 1.25 mg		Fingolimod 0.5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/429 (11.9%)		43/425 (10.1%)		56/418 (13.4%)
Blood and lymphatic system disorders
Leukopenia	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Lymphopenia	2/429 (0.5%)		0/425 (0%)		0/418 (0%)
Thrombocytopenia	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Cardiac disorders
Angina pectoris	1/429 (0.2%)		1/425 (0.2%)		0/418 (0%)
Atrioventricular block first degree	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Atrioventricular block second degree	1/429 (0.2%)		0/425 (0%)		1/418 (0.2%)
Bradycardia	3/429 (0.7%)		4/425 (0.9%)		1/418 (0.2%)
Left ventricular dysfunction	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Myocardial infarction	0/429 (0%)		0/425 (0%)		2/418 (0.5%)
Palpitations	1/429 (0.2%)		0/425 (0%)		1/418 (0.2%)
Pericarditis	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Supraventricular extrasystoles	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Tachycardia paroxysmal	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Ventricular tachycardia	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Eye disorders
Eye pain	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Iridocyclitis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Keratitis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Macular oedema	3/429 (0.7%)		0/425 (0%)		0/418 (0%)
Papilloedema	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Photopsia	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Retinal detachment	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Retinal disorder	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Retinitis	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Gastrointestinal disorders
Abdominal pain	0/429 (0%)		1/425 (0.2%)		1/418 (0.2%)
Abdominal pain upper	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Constipation	1/429 (0.2%)		0/425 (0%)		1/418 (0.2%)
Diarrhoea	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Dyspepsia	1/429 (0.2%)		0/425 (0%)		1/418 (0.2%)
Gastritis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Haemorrhoids	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Ileus paralytic	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Inguinal hernia	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Oesophagitis	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Pancreatitis chronic	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Vomiting	0/429 (0%)		1/425 (0.2%)		1/418 (0.2%)
General disorders
Chest pain	0/429 (0%)		2/425 (0.5%)		0/418 (0%)
Fatigue	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Haemorrhagic cyst	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Inflammation	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Non-cardiac chest pain	0/429 (0%)		2/425 (0.5%)		2/418 (0.5%)
Hepatobiliary disorders
Biliary colic	1/429 (0.2%)		1/425 (0.2%)		0/418 (0%)
Cholelithiasis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Cytolytic hepatitis	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Hepatic steatosis	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Hepatomegaly	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Infections and infestations
Abscess	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Abscess jaw	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Acute sinusitis	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Anal abscess	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Appendicitis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Clostridial infection	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Cystitis	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Dermo-hypodermitis	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Gastroenteritis	0/429 (0%)		1/425 (0.2%)		1/418 (0.2%)
Genital herpes	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Herpes virus infection	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Mastoiditis	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Otitis media acute	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Peritoneal abscess	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Peritonsillitis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Pharyngitis	0/429 (0%)		1/425 (0.2%)		1/418 (0.2%)
Pharyngotonsillitis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Pneumonia	1/429 (0.2%)		1/425 (0.2%)		0/418 (0%)
Pyelonephritis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Pyelonephritis acute	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Pyelonephritis chronic	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Respiratory tract infection	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Sinusitis	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Streptococcal abscess	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Tonsillitis	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Tooth abscess	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Upper respiratory tract infection	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Urinary tract infection	0/429 (0%)		2/425 (0.5%)		0/418 (0%)
Urosepsis	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Injury, poisoning and procedural complications
Burns second degree	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Fractured coccyx	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Head injury	0/429 (0%)		1/425 (0.2%)		1/418 (0.2%)
Ligament rupture	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Lower limb fracture	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Overdose	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Road traffic accident	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Splenic injury	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Splenic rupture	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Subdural haematoma	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Investigations
Alanine aminotransferase increased	1/429 (0.2%)		1/425 (0.2%)		0/418 (0%)
Aspartate aminotransferase increased	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Electrocardiogram PR prolongation	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Electrocardiogram change	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Gamma-glutamyltransferase increased	1/429 (0.2%)		1/425 (0.2%)		0/418 (0%)
Hepatic enzyme increased	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Liver function test abnormal	2/429 (0.5%)		0/425 (0%)		1/418 (0.2%)
Precancerous cells present	1/429 (0.2%)		1/425 (0.2%)		0/418 (0%)
Red blood cell sedimentation rate increased	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Metabolism and nutrition disorders
Dehydration	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Arthritis	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Back pain	0/429 (0%)		2/425 (0.5%)		1/418 (0.2%)
Bursitis	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Intervertebral disc protrusion	0/429 (0%)		0/425 (0%)		2/418 (0.5%)
Myalgia	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Pain in extremity	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/429 (0.2%)		4/425 (0.9%)		2/418 (0.5%)
Benign ovarian tumour	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Bowen's disease	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Brain neoplasm benign	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Breast cancer	1/429 (0.2%)		0/425 (0%)		3/418 (0.7%)
Cervix carcinoma stage 0	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Endometrial cancer	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Malignant melanoma	1/429 (0.2%)		0/425 (0%)		1/418 (0.2%)
Ovarian adenoma	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Prostate cancer	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Uterine leiomyoma	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Nervous system disorders
Amnesia	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Central nervous system lesion	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Cerebrovascular accident	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Epilepsy	2/429 (0.5%)		0/425 (0%)		0/418 (0%)
Grand mal convulsion	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Headache	2/429 (0.5%)		0/425 (0%)		0/418 (0%)
Ischaemic stroke	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Migraine with aura	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Monoplegia	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Multiple sclerosis	0/429 (0%)		2/425 (0.5%)		0/418 (0%)
Multiple sclerosis relapse	3/429 (0.7%)		2/425 (0.5%)		1/418 (0.2%)
Partial seizures with secondary generalisation	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Presyncope	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Sciatica	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Somnolence	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Syncope	1/429 (0.2%)		1/425 (0.2%)		1/418 (0.2%)
Pregnancy, puerperium and perinatal conditions
Abortion	0/429 (0%)		0/425 (0%)		3/418 (0.7%)
Abortion spontaneous	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Psychiatric disorders
Acute psychosis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Anxiety	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Depression	2/429 (0.5%)		0/425 (0%)		1/418 (0.2%)
Homicidal ideation	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Renal and urinary disorders
Nephrolithiasis	1/429 (0.2%)		1/425 (0.2%)		0/418 (0%)
Renal colic	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Renal cyst	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Reproductive system and breast disorders
Cervical dysplasia	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Endometriosis	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Metrorrhagia	1/429 (0.2%)		0/425 (0%)		1/418 (0.2%)
Ovarian cyst	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Ovarian disorder	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Chronic obstructive pulmonary disease	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Dyspnoea exertional	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Pleurisy	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Pneumonia aspiration	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Productive cough	1/429 (0.2%)		0/425 (0%)		0/418 (0%)
Pulmonary embolism	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Pulmonary oedema	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Skin and subcutaneous tissue disorders
Rash macular	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Urticaria	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Vascular disorders
Circulatory collapse	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Hypertension	0/429 (0%)		0/425 (0%)		1/418 (0.2%)
Varicose vein	0/429 (0%)		1/425 (0.2%)		0/418 (0%)
Other (Not Including Serious) Adverse Events
	Fingolimod 1.25 mg		Fingolimod 0.5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	346/429 (80.7%)		355/425 (83.5%)		323/418 (77.3%)
Ear and labyrinth disorders
Vertigo	18/429 (4.2%)		18/425 (4.2%)		21/418 (5%)
Gastrointestinal disorders
Diarrhoea	40/429 (9.3%)		50/425 (11.8%)		30/418 (7.2%)
Nausea	38/429 (8.9%)		38/425 (8.9%)		36/418 (8.6%)
General disorders
Fatigue	46/429 (10.7%)		48/425 (11.3%)		45/418 (10.8%)
Infections and infestations
Bronchitis	39/429 (9.1%)		34/425 (8%)		15/418 (3.6%)
Influenza	40/429 (9.3%)		55/425 (12.9%)		41/418 (9.8%)
Nasopharyngitis	112/429 (26.1%)		115/425 (27.1%)		115/418 (27.5%)
Pharyngitis	25/429 (5.8%)		26/425 (6.1%)		23/418 (5.5%)
Rhinitis	18/429 (4.2%)		25/425 (5.9%)		25/418 (6%)
Sinusitis	27/429 (6.3%)		27/425 (6.4%)		19/418 (4.5%)
Upper respiratory tract infection	62/429 (14.5%)		73/425 (17.2%)		72/418 (17.2%)
Urinary tract infection	21/429 (4.9%)		34/425 (8%)		47/418 (11.2%)
Investigations
Alanine aminotransferase increased	49/429 (11.4%)		42/425 (9.9%)		16/418 (3.8%)
Gamma-glutamyltransferase increased	31/429 (7.2%)		22/425 (5.2%)		4/418 (1%)
Weight increased	14/429 (3.3%)		14/425 (3.3%)		22/418 (5.3%)
Metabolism and nutrition disorders
Hypercholesterolaemia	26/429 (6.1%)		24/425 (5.6%)		26/418 (6.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	26/429 (6.1%)		30/425 (7.1%)		33/418 (7.9%)
Back pain	45/429 (10.5%)		49/425 (11.5%)		28/418 (6.7%)
Pain in extremity	24/429 (5.6%)		28/425 (6.6%)		27/418 (6.5%)
Nervous system disorders
Dizziness	31/429 (7.2%)		31/425 (7.3%)		23/418 (5.5%)
Headache	113/429 (26.3%)		107/425 (25.2%)		96/418 (23%)
Paraesthesia	17/429 (4%)		23/425 (5.4%)		18/418 (4.3%)
Psychiatric disorders
Depression	25/429 (5.8%)		33/425 (7.8%)		28/418 (6.7%)
Insomnia	16/429 (3.7%)		21/425 (4.9%)		25/418 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	37/429 (8.6%)		43/425 (10.1%)		34/418 (8.1%)
Dyspnoea	25/429 (5.8%)		30/425 (7.1%)		19/418 (4.5%)
Oropharyngeal pain	17/429 (4%)		29/425 (6.8%)		29/418 (6.9%)
Vascular disorders
Hypertension	27/429 (6.3%)		26/425 (6.1%)		15/418 (3.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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

Name/Title	Study Director
Organization	Novartis Pharmaceuticals
Phone	862 778-8300
Email

Responsible Party:

Novartis

ClinicalTrials.gov Identifier:

NCT00289978

Other Study ID Numbers:

CFTY720D2301

First Posted:

Feb 10, 2006

Last Update Posted:

Apr 11, 2012

Last Verified:

Apr 1, 2012

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

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

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Investigators

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Study Results

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Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

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Other (Not Including Serious) Adverse Events

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Certain Agreements

Results Point of Contact