A Randomized, Placebo-Controlled, Phase II Study of Tetomilast in Active Ulcerative Colitis

Stefan Schreiber*, Ali Keshavarzian, Kim L. Isaacs, John Schollenberger, Juan P. Guzman, Cesare Orlandi, Stephen B. Hanauer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Background & Aims: Tetomilast (OPC-6535), a novel thiazole compound, inhibits phosphodiesterase-4 and proinflammatory functions of leukocytes including superoxide production and cytokine release. Methods: One hundred eighty-six patients with mildly to moderately active ulcerative colitis (Disease Activity Index [DAI] 4-11 points) from 35 centers were randomized to receive an oral, once-daily dose of placebo or tetomilast 25 mg or 50 mg for 8 weeks. Results: Percentages of patients reaching the primary end point (improvement as defined by reduction in DAI ≥3 at week 8) were not significantly different between placebo (35%) and either the 25 mg tetomilast (52%) or the 50 mg tetomilast (39%) groups (intent-to-treat population). Remission rates (DAI 0-1) were 7%, 16%, and 21%, respectively (not significant). Mean reduction in DAI at week 8 was greater in the 25-mg group than under placebo (2.8 ± 0.4 vs 1.7 ± 0.36, respectively, P = .041) and approached statistical significance in the 50-mg group (2.8 ± 0.46, P = .056). A post hoc analysis focusing on patients with high activity scores (baseline DAI 7-11) suggested differences between tetomilast and placebo that will require further investigation. No significant safety concerns were raised. Main adverse effects included gastrointestinal problems (nausea, vomiting) and were preferentially seen in the 50-mg tetomilast group. Conclusions: This phase II trial of tetomilast in ulcerative colitis did not achieve statistical significance for the primary end point. Secondary end points indicate a potential clinical activity of tetomilast. The post hoc analysis suggests that further clinical development should focus on patients with objective parameters of inflammation.

Original languageEnglish (US)
Pages (from-to)76-86
Number of pages11
Issue number1
StatePublished - Jan 2007

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology


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