BACKGROUND: Dersalazine sodium is an inhibitor of platelet activator factor with potential efficacy in patients with ulcerative colitis through an alternative mechanism of action. The study was a first proof of clinical safety and activity of dersalazine sodium in patients with ulcerative colitis. METHODS: A double-blind study of randomized patients with ulcerative colitis (Mayo score >/= 5 and </= 10, including a sigmoidoscopy subscore >/= 2) to dersalazine sodium 1200 mg/12 h, mesalazine 1200 mg/12 h, or placebo for 4 weeks. Mayo scores were calculated on week 2 (partial Mayo) and week 4 (full Mayo). All patients received open-label mesalazine for 4 additional weeks, and a final visit was done at week 8. RESULTS: The study included 34 patients (13 dersalazine sodium, 10 mesalazine, and 11 placebo). Clinical remission was observed in 46.2% patients treated with dersalazine sodium versus 12.5% in mesalazine and 10% in placebo after 4 weeks of treatment. Colon biopsies showed significantly decreased expression of inflammatory genes in dersalazine sodium patients. Adverse events at least possibly related to treatment were observed in 23%, 12.5%, and 7.6% of patients receiving dersalazine sodium, mesalazine, and placebo, respectively; no serious adverse reactions were reported. Increased liver enzymes were reported in 2/13 patients receiving dersalazine sodium, with normal bilirubin levels; both returned to normal values on treatment interruption. CONCLUSIONS: Studies in wider populations are needed to confirm the clinical activity of dersalazine sodium. Weekly measurements of liver function tests may be necessary for early detection of adverse events.