Safety and activity of dersalazine sodium in patients with mild-to-moderate active colitis: double-blind randomized proof of concept study

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00808977.