Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Double-blind, Three-arm, Placebo-controlled, Multi-center Study to Evaluate the Safety and Efficacy of Oral Cladribine in Subjects With Relapsing-remitting Multiple Sclerosis (RRMS)
Brief Summary: The purpose of the study is to determine if cladribine tablets are a safe and effective treatment for relapsing-remitting multiple sclerosis (RRMS).


Options:
A: 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
B: 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
C: Part A

Key Inclusion Criteria:

* Must give written informed consent and any authorizations required by local law.
* Must have a diagnosis of relapsing-remitting MS, as defined by the revised McDonald criteria 1 through 4 (Polman et al, 2005). All other possible neurologic diagnoses must have been reasonably excluded by means of laboratory and/or imaging studies, in the opinion of the Investigator.
* Japanese men and women aged 18 to 65, inclusive, at the time of informed consent.
* All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be able to continue contraception for 12 weeks after their last dose of study treatment.
* Must have an Expanded Disability Status Scale (EDSS) score between 0.0 and 6.0, inclusive.
* Must have experienced at least 1 medically documented clinical exacerbation within 12 months of enrollment.
* Must be willing to remain free from concomitant immunosuppressive or immunomodulatory treatment (including interferon beta \[IFNβ\] and chronic systemic corticosteroids) for the duration of the study.
* Must have a baseline MRI, conducted within 35 calendar days prior to enrollment.

Key Exclusion Criteria:

* Diagnosis or history of neuromyelitis optica (NMO), e.g., a long spinal lesion extending over 3 or more vertebral bodies was detected, or the subject has a history of positive tests for anti-aquaporin-4 (anti-AQP4) antibodies.
* The subject is considered by the Investigator to be immunocompromised, based on medical history, physical examination, laboratory testing, or prior immunosuppressive or immunomodulating treatment.
* An MS exacerbation (relapse) within 30 days prior to enrollment or, in the opinion of the Investigator, the subject has not stabilized from a relapse prior to enrollment at Week 0.
* History of malignancy.
* Known history of, or positive test result for human immunodeficiency virus (HIV) infection.
* Known history of or positive test result for hepatitis C virus or hepatitis B virus within the year prior to enrollment.
* History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
* A clinically significant infectious illness within 30 days prior to enrollment.
* Abnormal liver function test results at screening: alanine aminotransferase (ALT), or aspartate aminotransferase (AST) \>2 times of the upper limit of normal (ULN) or bilirubin \>1.5 times of the ULN during screening.
* Previous treatment with natalizumab, any murine protein, or any other therapeutic monoclonal antibody.
* Any prior treatment with any of the following medications: total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination.
* Treatment with immunosuppressant medications, e.g., azathioprine, cyclophosphamide, methotrexate, and fingolimod within 6 months prior to enrollment, or mitoxantrone and cyclosporine within 12 months prior to enrollment.
* Treatment with any of the following medications or procedures within 6 months prior to enrollment: intravenous immunoglobulin (IVIg), plasmapheresis, or cytapheresis.
* Treatment with immunomodulatory medications (including IFNβ and glatiramer acetate \[GA\]) within 2 weeks of enrollment.
* Treatment with any of the following medications within 30 days of enrollment: intravenous corticosteroid treatment, systemic corticosteroid treatment, 4-aminopyridine or related products.
* Participation in any other investigational treatment within the 6 months prior to enrollment or concurrent with this study.

Part B

Key Inclusion Criteria:

* Must give written informed consent and any authorizations required by local law.
* Must have a diagnosis of relapsing-remitting MS, as defined by the revised McDonald criteria 1 through 4 (Polman et al, 2005). All other possible neurologic diagnoses must have been reasonably excluded by means of laboratory and/or imaging studies, in the opinion of the Investigator.
* Japanese men and women aged 18 to 65, inclusive, at the time of informed consent.
* All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be able to continue contraception for 12 weeks after their last dose of study treatment.
* Must have an EDSS score between 0.0 and 5.5, inclusive.
* Must have experienced at least 1 medically documented clinical exacerbation within 12 months of enrollment.
* Must be willing to remain free from concomitant immunosuppressive or immunomodulatory treatment (including IFNβ and chronic systemic corticosteroids) for the duration of the study.
* Prior to enrollment all subjects must have: a screening MRI, or documentation of an MRI within the subject's medical record within 1 year of the screening visit, which reveals 3 or more T2 hyperintense lesions consistent with MS, and a baseline MRI, conducted within 7 calendar days prior to enrollment, which reveals at least 1 MRI lesion consistent with MS.

Key Exclusion Criteria

* Diagnosis or history of NMO, e.g., a long spinal lesion extending over 3 or more vertebral bodies was detected, or the subject has a history of positive tests for anti-AQP4 antibodies.
* The subject is considered by the Investigator to be immunocompromised, based on medical history, physical examination, laboratory testing, or prior immunosuppressive or immunomodulating treatment.
* An MS exacerbation (relapse) within 30 days prior to enrollment or, in the opinion of the Investigator, the subject has not stabilized from a relapse prior to enrollment at Week 0.
* History of malignancy.
* Known history, or positive test result of HIV infection.
* Known history of or positive test result for hepatitis C virus or hepatitis B virus within the year prior to Enrollment.
* History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
* A clinically significant infectious illness within 30 days prior to Enrollment.
* Abnormal liver function test results at screening: ALT or AST \>2 times of the ULN or bilirubin \>1.5 times of the ULN during screening.
* Previous treatment with natalizumab, any murine protein, or any other therapeutic monoclonal antibody.
* Any prior treatment with any of the following medications: total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination.
* Treatment with immunosuppressant medications, e.g., azathioprine, cyclophosphamide, methotrexate, and fingolimod within 6 months prior to enrollment, or mitoxantrone and cyclosporine within 12 months prior to enrollment.
* Treatment with any of the following medications or procedures within 6 months prior to enrollment: IVIg, plasmapheresis, or cytapheresis.
* Treatment with immunomodulatory medications (including IFNβ and GA) within 2 weeks of enrollment.
* Treatment with any of the following medications within 30 days of enrollment: intravenous corticosteroid treatment, systemic corticosteroid treatment, 4-aminopyridine or related products.
* Participation in any other investigational treatment within the 6 months prior to enrollment or concurrent with this study.

NOTE: Other protocol defined inclusion/exclusion criteria may apply.
D: Inclusion Criteria:

* Male or female, between 18 and 65 years of age (inclusive, at time of informed consent)
* Has definite MS according to the McDonald criteria
* Has relapsing-remitting disease with 1 or more relapses within 12 months prior to Study Day 1
* Must have been clinically stable and not has a relapse within 28 days prior to Study Day 1
* Has MRI consistent with MS at the pre-study evaluation according to the Fazekas criteria
* Has a EDSS score from 0 to 5.5, inclusive
* Weighed between 40-120 kilogram (kg), inclusive
* If female, she must:

  1. be post-menopausal or surgically sterilized; or
  2. uses a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and
  3. be neither pregnant nor breast-feeding
* If male, he must be willing to use contraception to avoid pregnancies
* Be willing and able to comply with study procedures for the duration of the study
* Voluntarily provides written informed consent, and for United states of America (USA) sites only, a subject authorization under Health Insurance Portability and Accountability Act (HIPAA)

Exclusion Criteria:

* Has secondary progressive MS (SPMS) or primary progressive MS (PPMS)
* Prior use of disease modifying drugs (DMDs) within the last 3 months, or 2 or more prior treatment failures with DMDs on the basis of efficacy
* Has significant leukopenia (white blood cell count less than 0.5 times the lower limit of normal of the central laboratory) within 28 days prior to Study Day 1
* Has received cladribine, mitoxantrone, total lymphoid irradiation, myelosuppressive therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab
* Has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to Study Day 1
* Has compromised immune function or infection
* Has received oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days prior to Study Day 1
* Has received cytokine-based therapy, intravenous immunoglobulin therapy, or plasmapheresis within 3 months prior to Study Day 1
* Has platelet and absolute neutrophil counts below the lower limit of normal range within 28 days prior to Study Day 1
* Has prior or current history of malignancy
* Has a history of persistent anemia, leukopenia, neutropenia, or thrombocytopenia after immunosuppressive therapy
* Has systemic disease that, in the opinion of the Investigator, might interfere with subject safety, compliance or evaluation of the condition under Study (for example, insulin-dependent diabetes, Lyme disease, clinically significant cardiac, hepatic, or renal disease, Human Immunodeficiency Virus, or Human T-Cell Lymphotrophic Virus Type-1)
* Has a psychiatric disorder that, in the opinion of the Investigator, was unstable or would preclude safe participation in the study
* Has allergy or hypersensitivity to gadolinium, to cladribine or any of its excipients
* Has used any investigational drug or experimental procedure within 6 months prior to Study Day 1

Answer: D