Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008;10(11):259.
Epub 2008 Nov 12.

Evaluation of GW406381 for treatment of osteoarthritis of the knee: two randomized, controlled studies

Diane J Boswell  1 , Keld Ostergaard, Richard S Philipson, Rachel A Hodge, David Blum, Judith C Brown, Steve N Quessy
Affiliations

Evaluation of GW406381 for treatment of osteoarthritis of the knee: two randomized, controlled studies

Diane J Boswell et al. Medscape J Med. 2008.

Abstract

Context: GW406381 is an investigational, highly selective cyclooxygenase-2 (COX-2) inhibitor that is effective in animal models of central sensitization and of inflammatory pain.

Objective: To examine dose response for efficacy and safety of GW406381 in adults with osteoarthritis (OA) of the knee.

Design: Two randomized, double-blind, placebo- and positive-control studies: Study A, a 6-week nonflare design; Study B, a 12-week flare design.

Patients: 649 patients entered Study A; 1331 patients entered Study B.

Study a: GW406381 10, 20, 35, or 50 mg, celecoxib 200 mg, or placebo. Study B: GW406381 1, 5, 10, 25, or 50 mg, celecoxib 200 mg, or placebo.

Main outcome measures: Study A, co-primary endpoints were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore and WOMAC question 1. Study B co-primary endpoints were change from baseline in WOMAC pain and function subscores and Patient Global Assessment of Arthritis Condition. A closed hierarchical test procedure was prespecified.

Results: Study A demonstrated that GW406381 50 mg was superior to placebo on WOMAC pain subscore (mean difference from placebo -6.9 mm; P= .012). No clear dose response was observed, and the results with celecoxib were no different from those of placebo. In Study B, no dose of GW406381 was superior to placebo on the co-primary endpoints. Celecoxib was superior to placebo on all co-primary endpoints. Dose-related blood pressure and renovascular effects were seen with GW406381.

Conclusions: Overall, clinically meaningful efficacy in pain related to OA of the knee was not demonstrated for GW406381 despite its peripheral and central sites of action.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Adjusted mean change from baseline at each visit for WOMAC pain subscore in Study A. Pain scores on 0- to 100-mm scale.
Figure 2
Figure 2
Adjusted mean change from baseline at each visit for WOMAC pain Q1 (walking on a flat surface) score in Study A. Pain scores on 0- to 100-mm scale.
Figure 3
Figure 3
Adjusted mean change from baseline at each visit for WOMAC pain subscore in Study B. Pain scores on 0- to 100-mm scale.
Figure 4
Figure 4
Adjusted mean change from baseline at each visit for WOMAC pain Q1 (walking on a flat surface) score in Study B. Pain scores on 0- to 100-mm scale.
See this image and copyright information in PMC

References

    1. Haq I, Murphy E, Dacre J. Osteoarthritis. Postgrad Med J. 2003;79:377–383. - PMC - PubMed
    1. Jordan KM, Arden NK, Doherty M, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT) Ann Rheum Dis. 2003;62:1145–1155. - PMC - PubMed
    1. Schaible HG, Ebersberger A, von Banchet GS. Mechanisms of pain in arthritis. Ann N Y Acad Sci. 2002;966:343–354. - PubMed
    1. Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004;361:184–187. - PubMed
    1. Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease; potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001;44:1237–1247. - PubMed

LinkOut - more resources