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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01497262
• Collaborator: (none)
• Enrollment: 162
• Locations: 29
• Arm: 1
• Duration (Months): 26
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This 4 month, open-label study will evaluate the safety and tolerability of fingolimod 0.5 mg in patients with relapsing-remitting multiple sclerosis (RRMS) and generate additional data in Multiple Sclerosis (MS) patient population that closely resembles the clinical population seen in routine medical care.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Fingolimod	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 162 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 4-month, Open-label, Multi-center Study to Explore the Safety and Tolerability of Fingolimod 0.5 mg in Patients With Relapsing-remitting Multiple Sclerosis
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fingolimod Open-label fingolimod 0.5 mg, taken orally once daily for 4 months	Drug: Fingolimod; Fingolimod will be supplied as 0.5mg capsules in bottles of 35.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [28 weeks]

   Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity

Secondary Outcome Measures

1. Number (%) of Patients With AE of Special Interest Including Bradyarrhythmia, BP Increase, Liver Transaminase Elevations, Infections , Macula Oedema. [4 months]

   The incidence of events in special areas of safety interest (including bradyarrhythmias, BP increase, liver function, infections and macular oedema) were assessed by the nature and frequency of AE reporting. These areas of special interest have been identified and potential risks of fingolimod based on knowledge from clinical trials and post-marketing reporting.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with relapsing remitting Multiple Sclerosis

• Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5.

Exclusion Criteria:

• Patients with MS other than relapsing remitting MS

• Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.

• Patients who have been treated with:

• systemic corticosteroids or immunoglobulins within 1 month prior to baseline;

• immunosuppressive medications within 3 months prior to baseline;

• monoclonal antibodies within 3 months prior to baseline;

• cladribine, mitoxantrone or alemtuzumab at any time.

• Uncontrolled diabetes mellitus at screening

• Diagnosis of macular edema during Screening Phase

• Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or to have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests.

• Patients who have received total lymphoid irradiation or bone marrow transplantation.

• Patients with certain cardiovascular conditions and/or findings in the screening ECG

• Patients with certain liver conditions

• Pregnant confirmed by a positive pregnancy test t or nursing (lactating) women

• Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Caba	Buenos Aires	Argentina	1425
2	Novartis Investigative Site	Guaymallen	Mendoza	Argentina	M5507XAD
3	Novartis Investigative Site	San Miguel de Tucuman	Tucumán	Argentina	T4000DPB
4	Novartis Investigative Site	San Miguel de Tucumán	Tucumán	Argentina	4000
5	Novartis Investigative Site	Cordoba		Argentina	X5004CDT
6	Novartis Investigative Site	Salta		Argentina	A4400ANG
7	Novartis Investigative Site	Salta		Argentina	A4400BKZ
8	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	20270-004
9	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	21941-590
10	Novartis Investigative Site	Porto Alegre	RS	Brazil	90610-000
11	Novartis Investigative Site	Barranquilla	Atlantico	Colombia
12	Novartis Investigative Site	Bogotá	Cundinamarca	Colombia	110111
13	Novartis Investigative Site	Bogotá		Colombia	00000
14	Novartis Investigative Site	Bogotá		Colombia
15	Novartis Investigative Site	Cali		Colombia
16	Novartis Investigative Site	Amman		Jordan	11942
17	Novartis Investigative Site	Irbid		Jordan	22110
18	Novartis Investigative Site	Kuala Lumpur		Malaysia	50586
19	Novartis Investigative Site	Kuala Lumpur		Malaysia	59100
20	Novartis Investigative Site	Penang		Malaysia	10990
21	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	06700
22	Novartis Investigative Site	México	Distrito Federal	Mexico	10700
23	Novartis Investigative Site	Monterrey	Nuevo León	Mexico	64060
24	Novartis Investigative Site	San Nicolas De Los Garza	Nuevo León	Mexico	66480
25	Novartis Investigative Site	San Luis Potosí		Mexico	78240
26	Novartis Investigative Site	Panama City	Panamá	Panama
27	Novartis Investigative Site	La Perla	Callao	Peru	04
28	Novartis Investigative Site	Jesus Maria	Lima	Peru	11
29	Novartis Investigative Site	San Isidro	Lima	Peru	27

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01497262
• Other Study ID Numbers: CFTY720D2325
• First Posted: Dec 22, 2011
• Last Update Posted: Mar 19, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Multiple Sclerosis; Relapsing-Remitting
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Fingolimod Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Fingolimod 0.5 mg
Arm/Group Description	Open-label fingolimod 0.5 mg, taken orally once daily for 4 months
Period Title: Overall Study
STARTED	162
COMPLETED	151
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Fingolimod 0.5 mg
Arm/Group Description	Open-label fingolimod 0.5 mg, taken orally once daily for 4 months
Overall Participants	162
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	37.3 (9.67)
Age, Customized (Number) [Number]
<18 years	0 0%
18-30 years	47 29%
31-40 years	60 37%
41-55 years	47 29%
56-65 years	8 4.9%
>65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	114 70.4%
Male	48 29.6%

Outcome Measures

1. Secondary Outcome

Title	Number (%) of Patients With AE of Special Interest Including Bradyarrhythmia, BP Increase, Liver Transaminase Elevations, Infections , Macula Oedema.
Description	The incidence of events in special areas of safety interest (including bradyarrhythmias, BP increase, liver function, infections and macular oedema) were assessed by the nature and frequency of AE reporting. These areas of special interest have been identified and potential risks of fingolimod based on knowledge from clinical trials and post-marketing reporting.
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

Safety set includes all patients who received at least one dose of study drug

Arm/Group Title	Fingolimod 0.5 mg
Arm/Group Description	Open-label fingolimod 0.5 mg, taken orally once daily for 4 months
Measure Participants	162
Bradyarrhythmias	8.6 5.3%
Blood pressure increase	0.6 0.4%
Hypertension	2.5 1.5%
Liver Transaminase evaluations	3.7 2.3%
Infections	28.4 17.5%
Macula Oedema	0 0%

2. Primary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Description	Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

Safety set includes all patients who received at least one dose of study drug

Arm/Group Title	Fingolimod 0.5 mg
Arm/Group Description	Open-label fingolimod 0.5 mg, taken orally once daily for 4 months
Measure Participants	162
Adverse Events (AE)	100 61.7%
Serious Adverse Event (SAE)	12 7.4%
Deaths	0 0%

Adverse Events

Time Frame	Weeks 2,8, 16 and end of study visit
Adverse Event Reporting Description	Safety set includes all patients who took at least one dose of study drug
Arm/Group Title	Fingolimod 0.5 mg
Arm/Group Description	Open-label fingolimod 0.5 mg, taken orally once daily for 4 months
All Cause Mortality
	Fingolimod 0.5 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Fingolimod 0.5 mg
	Affected / at Risk (%)	# Events
Total	12/162 (7.4%)
Blood and lymphatic system disorders
Leukopenia	1/162 (0.6%)
Infections and infestations
Gastroenteritis	2/162 (1.2%)
Gastroenteritis viral	1/162 (0.6%)
Urinary tract infection	1/162 (0.6%)
Investigations
Fibrin D dimer increased	1/162 (0.6%)
White blood cell count decreased	1/162 (0.6%)
Nervous system disorders
Multiple sclerosis relapse	3/162 (1.9%)
Optic neuritis	1/162 (0.6%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/162 (0.6%)
Vascular disorders
Hypertension	1/162 (0.6%)
Other (Not Including Serious) Adverse Events
	Fingolimod 0.5 mg
	Affected / at Risk (%)	# Events
Total	63/162 (38.9%)
Blood and lymphatic system disorders
Lymphopenia	17/162 (10.5%)
Cardiac disorders
Bradycardia	6/162 (3.7%)
Eye disorders
Vision blurred	4/162 (2.5%)
Gastrointestinal disorders
Diarrhoea	8/162 (4.9%)
Nausea	5/162 (3.1%)
General disorders
Fatigue	10/162 (6.2%)
Infections and infestations
Influenza	4/162 (2.5%)
Upper respiratory tract infection	8/162 (4.9%)
Urinary tract infection	4/162 (2.5%)
Musculoskeletal and connective tissue disorders
Back pain	5/162 (3.1%)
Nervous system disorders
Dizziness	5/162 (3.1%)
Headache	22/162 (13.6%)
Psychiatric disorders
Anxiety	5/162 (3.1%)
Depression	4/162 (2.5%)

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 (ie, data from all sites) in the clinical trial.