Arthritis, Rheumatoid
Conditions
Keywords
iNOS, Exhaled NO, Rheumatoid arthritis
Brief summary
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.
Interventions
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurment of synovial vascularity | Day 1, Day 15 and Day 28 | Power Doppler ultrasonographic measurement of synovial vascularity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety: ECG | Day 1, 15 and 28 | 12-lead ECG meaurements |
| Safety: Vital Signs | Day 1, 15 and 28 | Blood pressure and heart rate |
| Safety: Laboratory | Day 1, 8, 15, 22, 28 and Follow Up | Laboratory assessments including liver function tests, amylase and lipase |
| Synovial thickness | Day 1, 15 and 28 | High frequency ultrasound measurement of synovial thickness |
| Pharmacokinetics: Trough | Days 8,15 and Day 28 | Trough plasma concentration of GW274150 |
| Tolerability | Day 1 to Day 28 and Follow Up | Adverse events |
| Pharmacokinetics: Cmax | Day 15 and Day 28 | Maximum plasma concentration of GW274150 |
Countries
Serbia, United Kingdom
Outcome results
None listed