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

Official Title: “A Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Investigate the Safety, Tolerability, Pharmacokinetics and Effect on Synovial Thickness and Vascularity of 28 Days Repeat Dosing of GW274150 or 7.5mg Prednisolone in RA Subjects.”

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.

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

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

Primary Measures

• Measurment of synovial vascularity
  • Time Frame: Day 1, Day 15 and Day 28
    Safety Issue?: No

Secondary Measures

• Synovial thickness
  • Time Frame: Day 1, 15 and 28
    Safety Issue?: No
• Safety: ECG
  • Time Frame: Day 1, 15 and 28
    Safety Issue?: No
• Safety: Vital Signs
  • Time Frame: Day 1, 15 and 28
    Safety Issue?: No
• Safety: Laboratory
  • Time Frame: Day 1, 8, 15, 22, 28 and Follow Up
    Safety Issue?: No
• Pharmacokinetics: Cmax
  • Time Frame: Day 15 and Day 28
    Safety Issue?: No
• Pharmacokinetics: Trough
  • Time Frame: Days 8,15 and Day 28
    Safety Issue?: No
• Tolerability
  • Time Frame: Day 1 to Day 28 and Follow Up
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: GlaxoSmithKline Industry

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00379990

Study ID Number: RA4104917

ClinicalTrials.gov Identifier: NCT00379990

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency