An extension of the 24-month, double-blind, randomized, multicenter, placebo-controlled, parallel-group study comparing efficacy and safety of FTY720 1.25 mg and 0.5 mg administered orally once daily versus placebo in patients with relapsing-remitting multiple sclerosis

1. Patients should complete the 24 month core study
2. Written informed consent provided prior to participation in extension study
3. Female patients at risk of becoming pregnant must have a negative pregnancy test and use simultaneously two forms of effective contraception

1. Premature discontinuation of the study drug during the core study FTY720D2301 due
to:
a. An adverse event or serious adverse event or laboratory abnormality, except
pregnancy
b. Conditions leading to permanent study drug discontinuation such as macular
edema, elevated liver enzymes five times ULN (upper limit of normal),
pulmonary function tests below 60% of baseline values. The full description of
these exclusion criteria and monitoring guidelines is outlined in Appendix 4:
Guidance on Safety Monitoring
2. Chronic disease of the immune system other than MS which may require
immunosuppressive treatment
3. History or presence of malignancy
4. Known diagnosis of diabetes mellitus or a blood glucose obtained suspicious for
diabetes (* 126 mg/dl or * 7 mmol/L if fasting; * 200 mg/dl or * 11.1 mmol/L if
random)
5. Macular edema during the core study
6. Active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis
B, Hepatitis C infection or have positive HIV antibody, Hepatitis B surface antigen or
Hepatitis C antibody tests
7. Previous treatment with cladribine, cyclophosphamide or mitoxantrone
8. Treatment with immunoglobulins and/or monoclonal antibodies (including
Natalizumab) in the past 3 months
9. Any medically unstable condition, that may interfere with the patient*s ability to
cooperate and comply with the study procedures, as assessed by the treating physician
10. Any of the following cardiovascular conditions:
a. myocardial infarction within the past 6 months prior to entry in the extension
study or with current unstable ischemic heart disease;
b. cardiac failure (Class III, according to New York Heart Association
Classification) or any severe cardiac disease as determined by the investigator;
c. arrhythmia requiring current treatment with Class III antiarrhythmic drugs
(e.g., amiodarone, bretylium, sotalol, ibulitide, azimilide, dofelitide)
d. history or presence of a third degree AV block
This document (090095af80e8c6b5 in docbase CREDI_EH) has been digitally signed with external signatures using Entrust PKI.
Signatures manifested as of 11/9/2007 9:03:15 AM, signing status at this time: Completed (2 of 2 signatures)
Approved for report publication by Zhang Zheng in East Hanover at Fri, 09 Nov 2007 08:58:46 AM EST
Approved for report publication by Agoropoulou Aikaterini in Basel at Fri, 09 Nov 2007 11:22:31 CET
Novartis Confidential Page 13
Clinical Study Protocol CFTY720D2301E1
e. proven history of sick sinus syndrome or sino-atrial heart block
f. known history of angina pectoris due to coronary spasm or Raynaud*s
phenomenon
11. Any of the following pulmonary conditions:
a. Severe respiratory disease or pulmonary fibrosis diagnosed [during the core
study]
b. History of tuberculosis
c. Abnormal chest x-ray or high resolution computer tomography (HRCT) [at
selected sites] suggestive of active pulmonary disease in the core study
12. Known history of alcohol abuse, chronic liver disease
13. Current participation in any clinical research study evaluating another investigational
drug or therapy
14. Female patients that are nursing (lactating)