Digestive Diseases and Sciences

, Volume 52, Issue 2, pp 442–450

A Randomized, Double-Blind, One-Week Study Comparing Effects of a Novel COX-2 Inhibitor and Naproxen on the Gastric Mucosa

  • James B. Moberly
  • Stuart I. Harris
  • Dennis S. Riff
  • James Craig Dale
  • Tara Breese
  • Patrick McLaughlin
  • Janet Lawson
  • Yaping Wan
  • Jianbo Xu
  • Kenneth E. Truitt
Original Article

DOI: 10.1007/s10620-006-9521-6

Cite this article as:
Moberly, J.B., Harris, S.I., Riff, D.S. et al. Dig Dis Sci (2007) 52: 442. doi:10.1007/s10620-006-9521-6

Abstract

CS-706 is a novel cyclooxygenase-2 (COX-2) inhibitor with potent analgesic, anti-inflammatory, and antitumor properties in animal models. This one-week, multicenter study was undertaken to assess the safety and tolerability of CS-706 and to compare the effects of CS-706 versus naproxen on acute gastrointestinal (GI) mucosal injury. Healthy men and women (n=160) without evidence of underlying gastroduodenal lesions were randomized to placebo, 100 mg CS-706 once daily, 200 mg CS-706 once daily, or 500 mg naproxen twice daily, administered for 7 days. On Day 8, subjects underwent a posttreatment upper GI endoscopy to assess development of gastroduodenal petechiae, erosions, and ulcers. Inhibition of COX-1 and COX-2 activity over the 24-hr postdose interval on Day 7 was determined in 48 subjects (12 per treatment group). CS-706 was safe and well tolerated. The extent of upper GI mucosal injury for both CS-706 dose groups was statistically significantly less than that for naproxen (P < 0.001) and was similar to placebo (P=0.615 and P=0.115 for 100 and 200 mg CS-706, respectively). No subject in placebo or either CS-706 treatment group had gastroduodenal ulcers, compared with 11 (28.2%) subjects treated with naproxen (P < 0.001). Both doses of CS-706 inhibited COX-2 activity to a similar extent as naproxen, whereas neither dose of CS-706 showed meaningful inhibition of platelet COX-1. In contrast, naproxen nearly completely inhibited COX-1 over the dosing interval. We conclude that CS-706, dosed up to 200 mg once daily, has an acute, upper GI toxicity profile similar to that of placebo and significantly superior to that of naproxen.

Keywords

CyclooxygenaseUpper GI endoscopyNSAID-induced ulcersErosionsThromboxaneProstaglandin

Copyright information

© Springer Science&#x002B;Business Media, Inc. 2006

Authors and Affiliations

  • James B. Moberly
    • 1
  • Stuart I. Harris
    • 2
  • Dennis S. Riff
    • 3
  • James Craig Dale
    • 4
  • Tara Breese
    • 4
  • Patrick McLaughlin
    • 3
  • Janet Lawson
    • 4
  • Yaping Wan
    • 5
  • Jianbo Xu
    • 1
  • Kenneth E. Truitt
    • 1
  1. 1.Daiichi Sankyo Pharma DevelopmentEdisonUSA
  2. 2.Sea View Research, Inc.MiamiUSA
  3. 3.Advanced Clinical Research InstituteAnaheimUSA
  4. 4.SCIREX CorporationAustinUSA
  5. 5.SCIREX CorporationBloomingdaleUSA