Randomised, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study to Investigate the MRI Efficacy and the Safety of Six Months' Administration of Firategrast (150 – 1200mg twice daily) in Subjects with Relapsing-Remitting Multiple Sclerosis

INTERVENTION: Product Name: Firategrast Product Code: SB683699 Pharmaceutical Form: Tablet CAS Number: 402567‐16‐2 Current Sponsor code: SB683699 Other descriptive name: Firategrast (USAN approved name) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Product Name: Firategrast Product Code: SB683699 Pharmaceutical Form: Tablet CAS Number: 402567‐16‐2 Current Sponsor code: SB683699 Other descriptive name: Firategrast (USAN approved name) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Relapsing‐Remitting Multiple Sclerosis ; MedDRA version: 8.1 Level: LLT Classification code 10063399 Term: Relapsing‐remitting multiple sclerosis PRIMARY OUTCOME: Main Objective: • To investigate the MRI efficacy of six months' administration of Firategrast in subjects with relapsing‐remitting MS Primary end point(s): The primary endpoint is the cumulative number of new gadolinium‐enhancing lesions on monthly MRI scans. MRI is an accepted surrogate marker of MS burden of disease for exploratory trials. Secondary Objective: To investigate the effect on the following parameters of 6 months' administration of Firategrast in subjects with relapsing‐remitting MS:; ‐ safety and tolerability; ‐ dose‐response relationship ; ‐ relationship between efficacy endpoints and systemic exposure to Firategrast and the metabolite GW786375X ; ‐ interaction between systemic exposure to Firategrast and systemic exposure to i.v. methylprednisolone during relapses; ‐ potential relationships between genetic variants and response to Firategrast, PK endpoints, and bilirubin levels; ‐ MS clinical scores; ‐ fatigue and employment status; ‐ utility of the Multiple Sclerosis Impact Scale (MSIS‐29) in clinical trials; INCLUSION CRITERIA: 1. Written informed consent 2. Males or females, aged 18 to 65, inclusive 3. Diagnosis of RRMS with dissemination in time and space 4. EDSS of between 0 and 6.0 inclusive at the Screening visit 5. Occurrence of at least two relapses in previous 24 months with at least 1 relapse or documented evidence of gadolinium‐enhancement on MRI (prior to screening) in the previous 12 months. Subject must not have had a relapse within 4 weeks prior to Screening. 6. Minimum of five T2 lesions on brain MRI at Visit 2 as determined by the central MRI analysis reader 7. A female subject is eligible to enter the study if she is of non‐childbearing potential or has a negative urine pregnancy test at Screening, and agrees to the consistent and correct use of agreed methods of contraception. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1