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

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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.

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Acknowledgments

The study was sponsored by Sankyo Pharma Development. We thank Mark Stiles (MDS Pharma Services Clinical Laboratory, Lincoln, Nebraska) for performing thromboxane B2 and prostaglandin E2 assays and Jennifer Scott and Strait Hicklin (SCIREX Corporation) for monitoring the study.

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Authors and Affiliations

  1. Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, New Jersey, 08837, USA

    James B. Moberly, Jianbo Xu & Kenneth E. Truitt

  2. Sea View Research, Inc., 3898 NW 7th Street, Miami, Florida, 33126, USA

    Stuart I. Harris

  3. Advanced Clinical Research Institute, 1211 West La Palma Avenue, Suite 602, Anaheim, California, 92801, USA

    Dennis S. Riff & Patrick McLaughlin

  4. SCIREX Corporation, 801 West 34th Street, Suite 200, Austin, Texas, 78705, USA

    James Craig Dale, Tara Breese & Janet Lawson

  5. SCIREX Corporation, 255 East Lake Street, Bloomingdale, Ilinois, 60108, USA

    Yaping Wan

Authors
  1. James B. Moberly
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  2. Stuart I. Harris
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  3. Dennis S. Riff
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  4. James Craig Dale
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  7. Janet Lawson
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  8. Yaping Wan
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  9. Jianbo Xu
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  10. Kenneth E. Truitt
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Correspondence to James B. Moberly.

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Moberly, J.B., Harris, S.I., Riff, D.S. et al. A Randomized, Double-Blind, One-Week Study Comparing Effects of a Novel COX-2 Inhibitor and Naproxen on the Gastric Mucosa. Dig Dis Sci 52, 442–450 (2007). https://doi.org/10.1007/s10620-006-9521-6

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  • DOI: https://doi.org/10.1007/s10620-006-9521-6

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