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

Condition(s) targeted: Arthritis, Rheumatoid

Intervention: GW274150 (Drug); Prednisolone (Drug); Placebo (Other)

Phase: Phase 2

Status: Completed

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

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.

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.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Measurment of synovial vascularity

Secondary outcome:

Synovial thickness

Safety: ECG

Safety: Vital Signs

Safety: Laboratory

Pharmacokinetics: Cmax

Pharmacokinetics: Trough

Tolerability

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

GSK Investigational Site, Belgrade 11000, Serbia

GSK Investigational Site, London W6 8LH, United Kingdom

Starting date: January 2006
Last updated: June 21, 2012