Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 6-month, Randomized, Active Comparator, Open-label, Multi-Center Study to Evaluate Patient OutComes, Safety and Tolerability of Fingolimod (FTY720) 0.5 mg/Day in Patients With Relapsing Forms of Multiple Sclerosis Who Are Candidates for MS Therapy Change From Previous Disease Modifying Therapy (EPOC)
Brief Summary: The purpose of this study is to evaluate the change in patient-reported outcomes, physician assessment of a change as well as safety and tolerability in patients with Relapsing Forms of Multiple Sclerosis on previous Disease Modifying Therapy (DMT) who are randomized to one of two treatment arms: fingolimod vs. standard of care DMT.


Options:
A: 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.
B: Core Study

Inclusion Criteria:

* Diagnosis of relapsing multiple Sclerosis (MS)
* Patients with at least two documented relapses in the previous 2 years or one documented relapse in the last year
* Patients with an Expanded Disability Status Scale (EDSS) score of 0-6

Extension Study

* A positive Gd-enhanced MRI scan at screening (in case the first MRI scan obtained at screening was negative, a second scan could have been obtained 1 month later)
* Neurologically stable with no evidence of relapse within 30 days prior to randomization,or during the Screening and Baseline periods.
* Female patients either post-menopausal, surgically incapable of bearing children, or practicing an acceptable method of birth control. Females of childbearing potential with a negative pregnancy test at baseline prior to entry into the treatment period.

Exclusion Criteria:

Core Study

* Patients with other chronic disease of the immune system, malignancies, pulmonary or heart disease, etc
* Pregnant or nursing women

Extension Study

* Patients who had permanently discontinued study drug prior to the Month 6 visit of the core study
* Patients with diabetes mellitus (to reduce the risk of ME), and therefore ongoing patients with diabetes mellitus or who developed diabetes mellitus were discontinued from the study)

Other protocol-defined inclusion/exclusion criteria may apply
C: Inclusion Criteria:

* Relapsing forms of MS
* Expanded Disability Status Scale (EDSS) 0-5.5
* Continuous treatment with MS DMT for a minimum of 6 months
* Fingolimod naive

Exclusion Criteria:

* Immune system diseases other than MS
* Active macular edema
* History of selected prior infections and criteria for immunizations
* History of selected immune system treatments and/or medications
* Selected cardiovascular, pulmonary, or hepatic conditions
* Selected abnormal laboratory values
* Pregnant or nursing women

Other protocol-defined inclusion/exclusion criteria applied
D: Inclusion Criteria:

General

1. sign written informed consent prior to participating in the study
2. 25 through 65 years of age inclusive
3. females of childbearing potential must:

   * have a negative pregnancy test at Baseline (prior to randomization) and
   * use simultaneously two forms of effective contraception during the treatment and 3-months after discontinuation of study medication

Primary Progressive Multiple sclerosis.

1. diagnosis of primary progressive multiple sclerosis (according to the 2005 Revised McDonald criteria):
2. time since first reported symptoms between 2 and 10 years
3. evidence of clinical disability progression in the 2 years prior to Screening
4. disability status at Screening

   * EDSS score of 3.5-6.0 inclusive
   * pyramidal functional system score of 2 or more
   * 25'TWT less than 30 seconds

Extension study Inclusion criteria

* Patients initially randomized to fingolimod 1.25 mg or placebo as part of the first study cohort, were to have completed at least 3 years on study drug treatment at the time of extension study initiation.
* Patients initially randomized to fingolimod 0.5 mg or placebo as part of the second study cohort, were to have continued on study drug treatment until such time as the last ongoing patient enrolled in the study had reached 3 years in study

Exclusion Criteria:

PPMS specific:

* History of relapses/attacks
* Progressive neurological disorder other than PPMS
* Pure cerebellar syndrome or pure visual progressive syndrome or pure
* cognitive progressive syndrome
* Presence of spinal cord compression at screening MRI
* Relevant history of vitamin B12 deficit
* Evidence of syphilis or borreliosis at Screening

Cardiovascular conditions:

* Myocardial infarction within the past 6 months or current unstable ischemic heart disease
* History of angina pectoris due to coronary spasm or history of Raynaud's phenomenon
* Severe cardiac failure or cardiac arrest
* History of symptomatic bradycardia
* Resting pulse \<55 bpm pre-dose
* History of sick sinus syndrome or sino-atrial heart block
* History or presence of second and third degree AV block or an increase QT interval (QTc\>440 ms)
* Arrythmia requiring treatment with class III antiarrythmic drugs
* History of positive tilt test from workout of vasovagal syncope
* Hypertension, not controlled with medication

Pulmonary:

* Severe respiratory disease or pulmonary fibrosis
* TB
* Abnormal X-ray, suggestive of active pulmonary disease
* Abnormal PFT: \<70% of predicted for FEV1 and FVC; \<60% for DLCO
* Patients receiving chronic (daily) therapies for asthma

Hepatic:

* Known history of alcohol abuse, chronic liver or biliary disease
* Total or conjugated Brb \>ULN, unless in context of Gilbert's syndrome
* AP \>1.5xULN; ALT/AST \>2xULN; GGT\>3xULN

Other:

* History of chronic disease of the immune system other than MS
* Malignancy (other than successfully treated SCC or BCC)
* Diabetes Mellitus
* Macular Edema present at screening
* HIV, Hepatitis C or B, other active infection
* History of total lymphoid irradiation or bone marrow transplantation
* Serum creatinine \>1.7 mg/dl
* WBC \<3500 cells/mm3
* Lymphocyte count \<800 cells/mm3
* History of substance abuse or any other factor that may interfere with subject ability to cooperate and comply with the study procedures
* Unable to undergo MRI scans
* Participation in any therapeutical clinical research study in the 6 months prior to randomization
* Pregnant or lactating women
* Drugs requiring wash-out period:

  3 months:
  * Systemic corticosteroids or ACTH
  * INF-beta

    6 months:
  * Immunosuppressive medication
  * Immunoglobulins
  * Monoclonal antibodies
* Drugs that exclude participation in the study:
* Cladribine
* Cyclophosphamide
* Mitoxantrone (except: patients who received a cumulative dose of no more than 60mg/m2 more than 5 years ago could enter the study)

Extension study Exclusion criteria

-Patients were not eligible for enrollment in the extension study if they had any of the following key exclusion criteria at the extension study Baseline visit: active chronic immune system disease other than MS (or stable disease treated with immune therapy); known immunodeficiency syndrome; active infection; uncontrolled diabetes mellitus; macularedema; treatment with Class Ia or III antiarrhythmic drugs; any of the specified cardiac, pulmonary, or hepatic conditions; or any medically unstable condition

Answer: C