BACKGROUND _ AIMS: Tetomilast ( @entity69877 ), a novel @entity6548 compound, inhibits phosphodiesterase-4 and proinflammatory functions of leukocytes including @entity224 production and cytokine release. METHODS: One hundred eighty-six @entity1 with mildly to moderately active @entity31 (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 @entity1 reaching the primary end point (improvement as defined by reduction in DAI > or =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 @entity1 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 @entity344 ( @entity390 , @entity391 ) and were preferentially seen in the 50-mg tetomilast group. CONCLUSIONS: This phase II trial of tetomilast in @entity31 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 @entity1 with objective parameters of @entity32 .

A randomized, placebo-controlled, phase II study of tetomilast in active XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity6548 :: ('CHEBI:43732', 'Chemical') :: ['thiazole'] @entity69877 :: ('MESH:C108965', 'Chemical') :: ['OPC-6535'] @entity390 :: ('MESH:D009325', 'Disease') :: ['nausea'] @entity31 :: ('MESH:D003093', 'Disease') :: ['ulcerative colitis'] @entity391 :: ('MESH:D014839', 'Disease') :: ['vomiting'] @entity344 :: ('MESH:D005767', 'Disease') :: ['gastrointestinal problems'] @entity224 :: ('MESH:D013481', 'Chemical') :: ['superoxide']
@entity31 :: (MESH:D003093,Disease) :: ['ulcerative colitis']
