A Study To Investigate GW274150 Or Prednisolone In Rheumatoid Arthritis Taken Repeatedly For 28 Days.

• Synovial thickness [ Time Frame: Day 1, 15 and 28 ] [ Designated as safety issue: No ]
  High frequency ultrasound measurement of synovial thickness
• Safety: ECG [ Time Frame: Day 1, 15 and 28 ] [ Designated as safety issue: No ]
  12-lead ECG meaurements
• Safety: Vital Signs [ Time Frame: Day 1, 15 and 28 ] [ Designated as safety issue: No ]
  Blood pressure and heart rate
• Safety: Laboratory [ Time Frame: Day 1, 8, 15, 22, 28 and Follow Up ] [ Designated as safety issue: No ]
  Laboratory assessments including liver function tests, amylase and lipase
• Pharmacokinetics: Cmax [ Time Frame: Day 15 and Day 28 ] [ Designated as safety issue: No ]
  Maximum plasma concentration of GW274150
• Pharmacokinetics: Trough [ Time Frame: Days 8,15 and Day 28 ] [ Designated as safety issue: No ]
  Trough plasma concentration of GW274150
• Tolerability [ Time Frame: Day 1 to Day 28 and Follow Up ] [ Designated as safety issue: No ]
  Adverse events

• High frequency ultrasound measurement of synovial thickness
• Pharmacokinetics of GW274150 at steady state
• Safety and tolerability including ECGs, lab tests, Adverse Events, vital signs.

This is an exploratory study to examine the effect of iNOS inhibition in rheumatoid arthritis patients. The study involves 28 days repeat dosing with GW274150 (dose determined by the results from a previous study), prednisolone (7.5mg) or placebo.

• Drug: GW274150
  60 mg /day
  Other Name: GW274150
• Drug: Prednisolone
  7.5 mg/day
  Other Name: Prednisolone
• Other: Placebo
  Placebo
  Other Name: Placebo

• Experimental: GW274150 60 mg once daily for 28 days
  60 mg GW274150 taken once daily for 28 days
  Intervention: Drug: GW274150
• Active Comparator: Prednisolone 7.5 mg once daily for 28 days
  7.5 mg prednisolone taken once daily for 28 days
  Intervention: Drug: Prednisolone
• Placebo Comparator: Placebo once daily for 28 days
  Placebo taken once daily for 28 days
  Intervention: Other: Placebo

Inclusion criteria:

• Diagnosis of rheumatoid arthritis according to the revised 1987 criteria of the American College of Rheumatology
• Female subjects who are not capable of becoming pregnant
• Active disease defined as Disease Activity Score (DAS) 28 = 4.0 and at least one metacarpal-phalangeal finger (MCP) joint with either detectable vascularity or thickness
• Stable doses of disease modifying anti-rheumatic drugs (DMARDs), (which can include but is not restricted to methotrexate, sulphasalazine and hydroxychloroquine in any combination) for 8 weeks prior to enrollment
• Patients receiving methotrexate must be on stable folate supplements
• Must have been on stable doses for 2 weeks prior to screening if using COX inhibitors
• Signed consent form
• The patient is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions

Exclusion criteria:

• The subject is using, or has used, oral glucocorticoids within 8 weeks of enrollment
• The subject is currently receiving anti-rheumatic biological therapy (e.g. infliximab, adalimumab, etanercept or anakinra)
• The subject received their final dose of infliximab or adalimumab within 3 months of enrollment
• The subject received their final dose of etanercept or anakinra within 1 month of enrollment
• The subject has received another investigational drug within 30 days
• The subject drinks more than 28 units (male) or 21 units (female) of alcohol in a week
• History of liver or renal disease in the 6 months prior to screening
• The subject has a history of drug or other allergy
• Subject is positive for Hepatitis B and C or HIV virus
• The subject has positive pregnancy test
• The subject has positive test for drugs of abuse