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

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.

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Other: Placebo; Drug: GW274150; Drug: Prednisolone

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Serbia
  • Belgrade, Serbia, 11000
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, W6 8LH
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GW274150 60 mg once daily for 28 days; 60 mg GW274150 taken once daily for 28 days	Drug: GW274150; 60 mg /day
Active Comparator: Prednisolone 7.5 mg once daily for 28 days; 7.5 mg prednisolone taken once daily for 28 days	Drug: Prednisolone; 7.5 mg/day
Placebo Comparator: Placebo once daily for 28 days; Placebo taken once daily for 28 days	Other: Placebo; Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: September 21, 2006
• First Submitted That Met QC Criteria: September 21, 2006
• First Posted (Estimate): September 25, 2006

Study Record Updates

• Last Update Posted (Estimate): July 2, 2012
• Last Update Submitted That Met QC Criteria: June 21, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis; iNOS; Exhaled NO
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone
• Other Study ID Numbers: RA4104917