Safety and Efficacy of Fingolimod in Pediatric Patients With Multiple Sclerosis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT01892722
• Collaborator: (none)
• Enrollment: 220
• Locations: 107
• Arms: 3
• Anticipated Duration (Months): 183.3
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To evaluate the safety and efficacy of fingolimod vs. interferon beta-1a i.m. in pediatric patients with multiple sclerosis (MS)

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Interferon beta-1a; Drug: Fingolimod; Drug: Placebo capsule; Drug: Placebo i.m. injection	Phase 3

Detailed Description

The study is divided into a Core Phase, which includes the Double-Blind Treatment Period, and an Extension Phase in which all patients will be treated with fingolimod. The Core Phase is a 24-month, double-blind, randomized, active-controlled, parallel-group multicenter study phase to evaluate the efficacy and safety of fingolimod compared to IFN β-1a in children/adolescent patients aged 10-17 years old with MS. The Extension Phase is a 60-month (5 year) study phase for patients who complete the Core Phase of the study and meet all inclusion/exclusion criteria and for patients who will be recruited in the younger cohort to participate in the Extension Phase. The 'younger cohort' refers to the population of pediatric patients fulfilling any single one or a combination of the following criteria: being ≤12 years of age, or weighing ≤40 kg, or being prepubertal (i.e. pubertal status of Tanner stage <2). The recruitment of the younger cohort (30 patients) was requested as a post- approval health authority commitment

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: There are 2 arms in the core phase. In the extension phase all participants are receiving open-label.study drug. A third arm has been added to enroll up to 30 new younger patients per HA post approval committment.There are 2 arms in the core phase. In the extension phase all participants are receiving open-label.study drug. A third arm has been added to enroll up to 30 new younger patients per HA post approval committment.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 2 Year, Double-blind, Randomized, Multicenter, Active-controlled Core Phase to Evaluate Safety & Efficacy of Daily Fingolimod vs Weekly Interferon β-1a im in Pediatric Patients With Multiple Sclerosis and 5 Year Fingolimod Extension Phase
• Actual Study Start Date: Jul 26, 2013
• Actual Primary Completion Date: Jul 14, 2017
• Anticipated Study Completion Date: Nov 2, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fingolimod Fingolimod was administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight) with the aim to achieve systemic exposure in range of that in adults at the licensed 0.5 mg dose. Participants in this arm during core continued into extension and received open-label treatment	Drug: Fingolimod; Administrated orally once daily: 0.5 mg capsule for patients over 40 kg or 0.25 mg capsule for patients 40 kg or less.; Drug: Placebo capsule; Matching placebo capsule required for double-dummy masking to blind formulations.
Active Comparator: Interferon beta-1a An intramuscular (IM) injection of Interferon beta-1a was administered once weekly during core phase. Participants switched to receive open-label fingolimod in extension phase	Drug: Interferon beta-1a; Administration once weekly via i.m. injections.; Drug: Placebo i.m. injection; Matching placebo i.m. injection required for double-dummy masking to blind formulations.
Experimental: Fingolimod-Younger Cohort The 'younger cohort' refers to the new pediatric patients to be recruited in the extension phase who fulfill any single one or a combination of the following criteria: being ≤12 years of age, or weighing ≤40 kg, or being prepubertal (i.e. pubertal status of Tanner stage <2)	Drug: Fingolimod; Administrated orally once daily: 0.5 mg capsule for patients over 40 kg or 0.25 mg capsule for patients 40 kg or less.

Outcome Measures

Primary Outcome Measures

1. Frequency of Relapses in Patients Treated for up to 24 Months [24 months]

   Frequency of relapses assessed by the annualized relapse rate (ARR). The ARR is defined as the average number of confirmed relapses per year (total number of confirmed relapses divided by the total days in the study multiplied by 365.25).

Secondary Outcome Measures

1. New/Newly Enlarged T2 Lesions [24 months]

   Annualized rate of the number of new/newly enlarged T2 lesions up to Month 24

2. Time to First Relapse [24 months]

   Time to first relapse was determined.

3. Proportion of Patients Relapse-free [24 months]

   Proportion of patients relapse-free was determined

4. T1 Gd- Enhancing Lesions [24 months]

   Number of T1 Gd-enhancing lesions per scan up to Month 24

5. Pharmacokinetics (Cavg) of Fingolimod-P [24 months]

   Cavg (average drug concentration over the dose interval) will be evaluated.

6. Pharmacokinetic/Pharmacodynamic Relationship for Fingolimod-P to Lymphocyte Levels [24 months]

   Population PK/PD modeling approaches were used to relate the individual fingolimod-P concentrations to lymphocyte counts.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria Core Phase:

• diagnosis of multiple sclerosis

• at least one MS relapse during the previous year or two MS relapses in the previous 2 years or evidence of Gd enhancing lesions on MRI within 6 months EDSS score of 0 to 5.5, inclusive

Key Exclusion Criteria Core Phase:

• patients with progressive MS

• patients with an active, chronic disease of the immune system other than MS

• patients meeting the definition of ADEM

• patients with severe cardiac disease or significant findings on the screening ECG.

• patients with severe renal insufficiency

Key Inclusion Criteria Extension Phase:

Applies to all patients participating in the Core Phase and then entering the Extension Phase. 1. Patients that originally met Core Phase Inclusion criteria and completed the Core phase on or off of study drug.

Applies to patients newly recruited to participate in the Extension Phase.

• All newly recruited patients' that enroll directly into the Extension Phase must fulfill the local country health authority product label approved for pediatric age group for inclusion criteria.

• Central review (including initial MRI report) of the diagnosis of pediatric MS will be required for all newly recruited patients.

Key Exclusion Criteria Extension Phase:

Applies to patients who completed the Core Phase, but prematurely discontinued study drug.

1. Premature discontinuation of the study drug during the Core Phase due to:

• an adverse event,

• serious adverse event,

• laboratory abnormality

• other conditions leading to permanent study drug discontinuation due to safety reasons

1. Patients with known new events or concomitant medications (washout periods required prior to Visit 15) that would exclude them from the Core Phase exclusion criteria. Serological or other additional tests will not be required.

Applies to patients newly recruited in the younger cohort to participate in the Extension Phase.

1. All newly recruited patients in the younger cohort that enroll directly into the Extension Phase must fulfill the exclusion criteria for the core phase.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35294
2	Novartis Investigative Site	Little Rock	Arkansas	United States	72202
3	Novartis Investigative Site	Los Angeles	California	United States	90027
4	Novartis Investigative Site	San Francisco	California	United States	94143
5	Novartis Investigative Site	Aurora	Colorado	United States	80045
6	Novartis Investigative Site	Miami	Florida	United States	33136
7	Novartis Investigative Site	Orlando	Florida	United States	32819
8	Novartis Investigative Site	Tallahassee	Florida	United States	32308
9	Novartis Investigative Site	Chicago	Illinois	United States	60611
10	Novartis Investigative Site	Boston	Massachusetts	United States	02114
11	Novartis Investigative Site	Boston	Massachusetts	United States	02115
12	Novartis Investigative Site	Detroit	Michigan	United States	48201
13	Novartis Investigative Site	New Brunswick	New Jersey	United States	08901
14	Novartis Investigative Site	Rochester	New York	United States	14642
15	Novartis Investigative Site	Stony Brook	New York	United States	11794
16	Novartis Investigative Site	Chapel Hill	North Carolina	United States	27599-9500
17	Novartis Investigative Site	Durham	North Carolina	United States	27710
18	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19104 4399
19	Novartis Investigative Site	Greenville	South Carolina	United States	29607
20	Novartis Investigative Site	San Antonio	Texas	United States	78229
21	Novartis Investigative Site	Salt Lake City	Utah	United States	84108
22	Novartis Investigative Site	Parkville	Victoria	Australia	3052
23	Novartis Investigative Site	Vienna		Austria	1090
24	Novartis Investigative Site	Minsk		Belarus	220114
25	Novartis Investigative Site	Belo Horizonte	Minas Gerais	Brazil	30150 221
26	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	20270-004
27	Novartis Investigative Site	Sao Paulo	SP	Brazil	05403-000
28	Novartis Investigative Site	Goiania		Brazil	74605 020
29	Novartis Investigative Site	Sofia		Bulgaria	1113
30	Novartis Investigative Site	Calgary	Alberta	Canada	T3B 6A8
31	Novartis Investigative Site	Ottawa	Ontario	Canada	K1H 8L1
32	Novartis Investigative Site	Osijek		Croatia	31000
33	Novartis Investigative Site	Tallinn		Estonia	10617
34	Novartis Investigative Site	Bordeaux Cedex		France	33076
35	Novartis Investigative Site	Le Kremlin Bicetre		France	94275
36	Novartis Investigative Site	Marseille Cedex 05		France	13885
37	Novartis Investigative Site	Montpellier		France	34295
38	Novartis Investigative Site	Toulouse Cedex		France	31059
39	Novartis Investigative Site	Bochum		Germany	44791
40	Novartis Investigative Site	Bonn		Germany	53111
41	Novartis Investigative Site	Dresden		Germany	01307
42	Novartis Investigative Site	Erlangen		Germany	91054
43	Novartis Investigative Site	Essen		Germany	45147
44	Novartis Investigative Site	Freiburg		Germany	79106
45	Novartis Investigative Site	Gottingen		Germany	37075
46	Novartis Investigative Site	Hamburg		Germany	20246
47	Novartis Investigative Site	Muenchen		Germany	80337
48	Novartis Investigative Site	Muenster		Germany	48149
49	Novartis Investigative Site	Bari	BA	Italy	70124
50	Novartis Investigative Site	Montichiari	BS	Italy	25018
51	Novartis Investigative Site	Catania	CT	Italy	95123
52	Novartis Investigative Site	Milano	MI	Italy	20132
53	Novartis Investigative Site	Cefalu	PA	Italy	90015
54	Novartis Investigative Site	Roma	RM	Italy	00133
55	Novartis Investigative Site	Roma	RM	Italy	00189
56	Novartis Investigative Site	Gallarate	VA	Italy	21013
57	Novartis Investigative Site	Napoli		Italy	80131
58	Novartis Investigative Site	Riga		Latvia	LV-1004
59	Novartis Investigative Site	Kaunas	LTU	Lithuania	LT 50161
60	Novartis Investigative Site	Ciudad De Mexico	D F	Mexico	06700
61	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	03310
62	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	04530
63	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	06720
64	Novartis Investigative Site	Merida	Yucatán	Mexico	97125
65	Novartis Investigative Site	Rotterdam		Netherlands	3015 CN
66	Novartis Investigative Site	Lodz		Poland	93-338
67	Novartis Investigative Site	Lublin		Poland	20-093
68	Novartis Investigative Site	Poznan		Poland	60-355
69	Novartis Investigative Site	Wroclaw		Poland	50 420
70	Novartis Investigative Site	Santurce		Puerto Rico	00912
71	Novartis Investigative Site	Bucuresti		Romania	041914
72	Novartis Investigative Site	Kazan		Russian Federation	420021
73	Novartis Investigative Site	Moscow		Russian Federation	119602
74	Novartis Investigative Site	Moscow		Russian Federation	119991
75	Novartis Investigative Site	Novosibirsk		Russian Federation	630087
76	Novartis Investigative Site	St. Petersburg		Russian Federation	197110
77	Novartis Investigative Site	Belgrade		Serbia	11000
78	Novartis Investigative Site	Kragujevac		Serbia	34000
79	Novartis Investigative Site	Novi Sad		Serbia	21000
80	Novartis Investigative Site	Bratislava	Slovensko	Slovakia	83340
81	Novartis Investigative Site	Malaga	Andalucia	Spain	29010
82	Novartis Investigative Site	Sevilla	Andalucia	Spain	41009
83	Novartis Investigative Site	Esplugues de Llobregat	Barcelona	Spain	08950
84	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
85	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46010
86	Novartis Investigative Site	Barakaldo	Pais Vasco	Spain	48903
87	Novartis Investigative Site	Vigo	Pontevedra	Spain	36212
88	Novartis Investigative Site	Madrid		Spain	28006
89	Novartis Investigative Site	Lund		Sweden	221 85
90	Novartis Investigative Site	Konak-Izmir	Izmir	Turkey	35210
91	Novartis Investigative Site	Istanbul	TUR	Turkey	34098
92	Novartis Investigative Site	Ankara		Turkey	06100
93	Novartis Investigative Site	Ankara		Turkey	06500
94	Novartis Investigative Site	Izmir		Turkey	35340
95	Novartis Investigative Site	Samsun		Turkey	55139
96	Novartis Investigative Site	Cherkasy		Ukraine	18000
97	Novartis Investigative Site	Dnipropetrovsk		Ukraine	49027
98	Novartis Investigative Site	Kharkiv		Ukraine	61068
99	Novartis Investigative Site	Kharkiv		Ukraine	61091
100	Novartis Investigative Site	Kiev		Ukraine	03110
101	Novartis Investigative Site	Lviv		Ukraine	79010
102	Novartis Investigative Site	Odesa		Ukraine	65009
103	Novartis Investigative Site	Vinnytsa		Ukraine	21029
104	Novartis Investigative Site	West Midlands	Birmingham	United Kingdom	B4 6NH
105	Novartis Investigative Site	Edinburgh		United Kingdom	EH9 1LF
106	Novartis Investigative Site	London		United Kingdom	WC1N 1EH
107	Novartis Investigative Site	London		United Kingdom	WC1N 3BG

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Nov 16, 2016
• Statistical Analysis Plan - Aug 4, 2017

More Information

Additional Information:

• Recruitment website

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01892722
• Other Study ID Numbers: CFTY720D2311; 2011-005677-23
• First Posted: Jul 4, 2013
• Last Update Posted: Jul 18, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: pediatric; multiple sclerosis; fingolimod; pre-pubertal; low weight; children; adolescent; MS; core phase; extension phase; younger cohort
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Interferons; Interferon-beta; Interferon beta-1a; Fingolimod Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	This study is divided into a core phase and extension phase. In the core phase, patients were randomized to Fingolimod or Interferon beta-1a in a 1:1 ratio. The core phase disposition is reported for interim results disclosure. Upon completion of the extension phase, the extension disposition will be reported.

Arm/Group Title	Fingolimod	Interferon Beta-1a
Arm/Group Description	Fingolimod was administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight) with the aim to achieve systemic exposure in range of that in adults at the licensed 0.5 mg dose.	An intramuscular (IM) injection of Interferon beta-1a was administered once weekly.
Period Title: Overall Study
STARTED	107	108
Full Analysis Set	107	107
COMPLETED	100	88
NOT COMPLETED	7	20

Baseline Characteristics

Arm/Group Title	Fingolimod	Interferon Beta-1a	Total
Arm/Group Description	Fingolimod was administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight) with the aim to achieve systemic exposure in range of that in adults at the licensed 0.5 mg dose.	An intramuscular (IM) injection of Interferon beta-1a was administered once weekly.	Total of all reporting groups
Overall Participants	107	108	215
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	15.2 (2.0)	15.4 (1.60)	15.3 (1.81)
Sex: Female, Male (Count of Participants)
Female	70 65.4%	64 59.3%	134 62.3%
Male	37 34.6%	44 40.7%	81 37.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 2.8%	2 1.9%	5 2.3%
Asian	1 0.9%	0 0%	1 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 0.9%	4 3.7%	5 2.3%
White	100 93.5%	97 89.8%	197 91.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.9%	5 4.6%	7 3.3%

Outcome Measures

1. Primary Outcome

Title	Frequency of Relapses in Patients Treated for up to 24 Months
Description	Frequency of relapses assessed by the annualized relapse rate (ARR). The ARR is defined as the average number of confirmed relapses per year (total number of confirmed relapses divided by the total days in the study multiplied by 365.25).
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): The FAS was comprised of all randomized patients with assigned treatments who received at least one dose of study medication.

Arm/Group Title	Fingolimod	Interferon Beta-1a
Arm/Group Description	Fingolimod was administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight) with the aim to achieve systemic exposure in range of that in adults at the licensed 0.5 mg dose.	An intramuscular (IM) injection of Interferon beta-1a was administered once weekly.
Measure Participants	107	107
Mean (95% Confidence Interval) [Confirmed relapse per year]	0.122	0.675

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fingolimod, Interferon Beta-1a
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Negative binomial regression model
	Comments

2. Secondary Outcome

Title	New/Newly Enlarged T2 Lesions
Description	Annualized rate of the number of new/newly enlarged T2 lesions up to Month 24
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Time to First Relapse
Description	Time to first relapse was determined.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Proportion of Patients Relapse-free
Description	Proportion of patients relapse-free was determined
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	T1 Gd- Enhancing Lesions
Description	Number of T1 Gd-enhancing lesions per scan up to Month 24
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Pharmacokinetics (Cavg) of Fingolimod-P
Description	Cavg (average drug concentration over the dose interval) will be evaluated.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Pharmacokinetic/Pharmacodynamic Relationship for Fingolimod-P to Lymphocyte Levels
Description	Population PK/PD modeling approaches were used to relate the individual fingolimod-P concentrations to lymphocyte counts.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for the primary endpoint. All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit for the primary endpoint, up to approximately 4 years. The trial is ongoing.
Arm/Group Title	Fingolimod		Interferon Beta-1a
Arm/Group Description	Fingolimod was administered orally once daily at a dose of either 0.5 mg or 0.25 mg (depending on patient's body weight) with the aim to achieve systemic exposure in range of that in adults at the licensed 0.5 mg dose.		An intramuscular (IM) injection of Interferon beta-1a was administered once weekly.
All Cause Mortality
	Fingolimod		Interferon Beta-1a
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/107 (0%)
Serious Adverse Events
	Fingolimod		Interferon Beta-1a
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/107 (17.8%)		10/107 (9.3%)
Blood and lymphatic system disorders
Agranulocytosis	1/107 (0.9%)		0/107 (0%)
Leukopenia	2/107 (1.9%)		0/107 (0%)
Cardiac disorders
Atrioventricular block second degree	1/107 (0.9%)		0/107 (0%)
Supraventricular tachycardia	0/107 (0%)		1/107 (0.9%)
Eye disorders
Autoimmune uveitis	1/107 (0.9%)		0/107 (0%)
Uveitis	0/107 (0%)		1/107 (0.9%)
Gastrointestinal disorders
Dyspepsia	1/107 (0.9%)		0/107 (0%)
Gastrointestinal necrosis	1/107 (0.9%)		0/107 (0%)
Gastrooesophageal reflux disease	0/107 (0%)		1/107 (0.9%)
Rectal tenesmus	1/107 (0.9%)		0/107 (0%)
Small intestinal obstruction	1/107 (0.9%)		0/107 (0%)
General disorders
Fatigue	0/107 (0%)		1/107 (0.9%)
Pyrexia	0/107 (0%)		1/107 (0.9%)
Infections and infestations
Abscess oral	1/107 (0.9%)		0/107 (0%)
Appendicitis	1/107 (0.9%)		0/107 (0%)
Cellulitis	1/107 (0.9%)		0/107 (0%)
Gastritis viral	0/107 (0%)		1/107 (0.9%)
Gastrointestinal infection	1/107 (0.9%)		0/107 (0%)
Paronychia	0/107 (0%)		1/107 (0.9%)
Viral infection	1/107 (0.9%)		0/107 (0%)
Viral pharyngitis	1/107 (0.9%)		0/107 (0%)
Injury, poisoning and procedural complications
Head injury	1/107 (0.9%)		0/107 (0%)
Humerus fracture	1/107 (0.9%)		0/107 (0%)
Investigations
Alanine aminotransferase increased	1/107 (0.9%)		0/107 (0%)
Body temperature increased	0/107 (0%)		1/107 (0.9%)
Gamma-glutamyltransferase increased	1/107 (0.9%)		0/107 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/107 (0.9%)		0/107 (0%)
Muscular weakness	1/107 (0.9%)		0/107 (0%)
Nervous system disorders
Dizziness	0/107 (0%)		1/107 (0.9%)
Epilepsy	1/107 (0.9%)		0/107 (0%)
Generalised tonic-clonic seizure	1/107 (0.9%)		0/107 (0%)
Headache	0/107 (0%)		1/107 (0.9%)
Migraine	1/107 (0.9%)		0/107 (0%)
Migraine without aura	1/107 (0.9%)		0/107 (0%)
Multiple sclerosis plaque	1/107 (0.9%)		0/107 (0%)
Multiple sclerosis relapse	1/107 (0.9%)		3/107 (2.8%)
Optic neuritis	0/107 (0%)		1/107 (0.9%)
Seizure	2/107 (1.9%)		0/107 (0%)
Sensory loss	0/107 (0%)		1/107 (0.9%)
Renal and urinary disorders
Bladder spasm	1/107 (0.9%)		0/107 (0%)
Dysuria	1/107 (0.9%)		0/107 (0%)
Skin and subcutaneous tissue disorders
Hypersensitivity vasculitis	1/107 (0.9%)		0/107 (0%)
Other (Not Including Serious) Adverse Events
	Fingolimod		Interferon Beta-1a
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/107 (76.6%)		94/107 (87.9%)
Blood and lymphatic system disorders
Leukopenia	14/107 (13.1%)		3/107 (2.8%)
Gastrointestinal disorders
Abdominal pain	9/107 (8.4%)		9/107 (8.4%)
Diarrhoea	8/107 (7.5%)		10/107 (9.3%)
Nausea	9/107 (8.4%)		5/107 (4.7%)
Toothache	6/107 (5.6%)		2/107 (1.9%)
Vomiting	8/107 (7.5%)		7/107 (6.5%)
General disorders
Chills	1/107 (0.9%)		11/107 (10.3%)
Fatigue	10/107 (9.3%)		6/107 (5.6%)
Influenza like illness	5/107 (4.7%)		40/107 (37.4%)
Pyrexia	8/107 (7.5%)		21/107 (19.6%)
Infections and infestations
Influenza	12/107 (11.2%)		4/107 (3.7%)
Nasopharyngitis	8/107 (7.5%)		5/107 (4.7%)
Rhinitis	10/107 (9.3%)		9/107 (8.4%)
Upper respiratory tract infection	17/107 (15.9%)		5/107 (4.7%)
Viral upper respiratory tract infection	23/107 (21.5%)		26/107 (24.3%)
Investigations
Glomerular filtration rate decreased	1/107 (0.9%)		6/107 (5.6%)
White blood cell count decreased	6/107 (5.6%)		0/107 (0%)
Musculoskeletal and connective tissue disorders
Back pain	6/107 (5.6%)		6/107 (5.6%)
Nervous system disorders
Headache	34/107 (31.8%)		31/107 (29%)
Psychiatric disorders
Anxiety	7/107 (6.5%)		2/107 (1.9%)
Respiratory, thoracic and mediastinal disorders
Cough	10/107 (9.3%)		12/107 (11.2%)
Oropharyngeal pain	9/107 (8.4%)		5/107 (4.7%)

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 or disclosure of trial results in their entirety.