Clinical trial NCT00379990: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Keywords: iNOS
Exhaled NO
Rheumatoid arthritis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-09-25
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Measurment of synovial vascularity
timeFrame: Day 1, Day 15 and Day 28
Secondary outcomes:
measure: Synovial thickness
timeFrame: Day 1, 15 and 28
measure: Safety: ECG
timeFrame: Day 1, 15 and 28
measure: Safety: Vital Signs
timeFrame: Day 1, 15 and 28
measure: Safety: Laboratory
timeFrame: Day 1, 8, 15, 22, 28 and Follow Up
measure: Pharmacokinetics: Cmax
timeFrame: Day 15 and Day 28
measure: Pharmacokinetics: Trough
timeFrame: Days 8,15 and Day 28
measure: Tolerability
timeFrame: Day 1 to Day 28 and Follow Up
Other outcomes:
Locations:
city: Belgrade
country: Serbia
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Seymour M, Petavy F, Chiesa F, Perry H, Lukey PT, Binks M, Donatien PD, Freidin AJ, Eckersley RJ, McClinton C, Heath K, Prodanovic S, Radunovic G, Pilipovic N, Damjanov N, Taylor PC. Ultrasonographic measures of synovitis in an early phase clinical trial: a double-blind, randomised, placebo and comparator controlled phase IIa trial of GW274150 (a selective inducible nitric oxide synthase inhibitor) in rheumatoid arthritis. Clin Exp Rheumatol. 2012 Mar-Apr;30(2):254-61. Epub 2012 Apr 13.