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

Primary Purpose

Arthritis, Rheumatoid

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GW274150
Prednisolone
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring iNOS, Exhaled NO, Rheumatoid arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

GW274150 60 mg once daily for 28 days

Prednisolone 7.5 mg once daily for 28 days

Placebo once daily for 28 days

Arm Description

60 mg GW274150 taken once daily for 28 days

7.5 mg prednisolone taken once daily for 28 days

Placebo taken once daily for 28 days

Outcomes

Primary Outcome Measures

Measurment of synovial vascularity
Power Doppler ultrasonographic measurement of synovial vascularity

Secondary Outcome Measures

Synovial thickness
High frequency ultrasound measurement of synovial thickness
Safety: ECG
12-lead ECG meaurements
Safety: Vital Signs
Blood pressure and heart rate
Safety: Laboratory
Laboratory assessments including liver function tests, amylase and lipase
Pharmacokinetics: Cmax
Maximum plasma concentration of GW274150
Pharmacokinetics: Trough
Trough plasma concentration of GW274150
Tolerability
Adverse events

Full Information

First Posted
September 21, 2006
Last Updated
June 21, 2012
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00379990
Brief Title
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

2. Study Status

Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
iNOS, Exhaled NO, Rheumatoid arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GW274150 60 mg once daily for 28 days
Arm Type
Experimental
Arm Description
60 mg GW274150 taken once daily for 28 days
Arm Title
Prednisolone 7.5 mg once daily for 28 days
Arm Type
Active Comparator
Arm Description
7.5 mg prednisolone taken once daily for 28 days
Arm Title
Placebo once daily for 28 days
Arm Type
Placebo Comparator
Arm Description
Placebo taken once daily for 28 days
Intervention Type
Drug
Intervention Name(s)
GW274150
Intervention Description
60 mg /day
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
7.5 mg/day
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Measurment of synovial vascularity
Description
Power Doppler ultrasonographic measurement of synovial vascularity
Time Frame
Day 1, Day 15 and Day 28
Secondary Outcome Measure Information:
Title
Synovial thickness
Description
High frequency ultrasound measurement of synovial thickness
Time Frame
Day 1, 15 and 28
Title
Safety: ECG
Description
12-lead ECG meaurements
Time Frame
Day 1, 15 and 28
Title
Safety: Vital Signs
Description
Blood pressure and heart rate
Time Frame
Day 1, 15 and 28
Title
Safety: Laboratory
Description
Laboratory assessments including liver function tests, amylase and lipase
Time Frame
Day 1, 8, 15, 22, 28 and Follow Up
Title
Pharmacokinetics: Cmax
Description
Maximum plasma concentration of GW274150
Time Frame
Day 15 and Day 28
Title
Pharmacokinetics: Trough
Description
Trough plasma concentration of GW274150
Time Frame
Days 8,15 and Day 28
Title
Tolerability
Description
Adverse events
Time Frame
Day 1 to Day 28 and Follow Up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
W6 8LH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
22409880
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.
Results Reference
derived

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

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