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

Study Overview
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Brief Summary
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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
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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.

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: GW274150
* Drug: Prednisolone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GW274150 60 mg once daily for 28 days<br>60 mg GW274150 taken once daily for 28 days | Drug: GW274150<br>* 60 mg /day<br>|
| Active Comparator: Prednisolone 7.5 mg once daily for 28 days<br>7.5 mg prednisolone taken once daily for 28 days | Drug: Prednisolone<br>* 7.5 mg/day<br>|
| Placebo Comparator: Placebo once daily for 28 days<br>Placebo taken once daily for 28 days | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurment of synovial vascularity | Power Doppler ultrasonographic measurement of synovial vascularity | Day 1, Day 15 and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Synovial thickness | High frequency ultrasound measurement of synovial thickness | Day 1, 15 and 28 | 
| Safety: ECG | 12-lead ECG meaurements | Day 1, 15 and 28 | 
| Safety: Vital Signs | Blood pressure and heart rate | Day 1, 15 and 28 | 
| Safety: Laboratory | Laboratory assessments including liver function tests, amylase and lipase | Day 1, 8, 15, 22, 28 and Follow Up | 
| Pharmacokinetics: Cmax | Maximum plasma concentration of GW274150 | Day 15 and Day 28 | 
| Pharmacokinetics: Trough | Trough plasma concentration of GW274150 | Days 8,15 and Day 28 | 
| Tolerability | Adverse events | Day 1 to Day 28 and Follow Up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iNOS, Exhaled NO, Rheumatoid arthritis