Randomised clinical trial: the clinical effects of a novel neurokinin receptor antagonist, DNK333, in women with diarrhoea-predominant irritable bowel syndrome.

Summary Background  Neurokinin receptors may play an important role in the visceral hypersensitivity and exaggerated motor/secretory activity associated with diarrhoea-predominant irritable bowel syndrome (IBS-D). Aim  To evaluate the effects of DNK333, a novel neurokinin antagonist, in women with IBS-D. Methods  In two consecutive phase II studies, women with IBS-D were randomised to twice-daily (b.d.) DNK333 25 mg, DNK333 100 mg or placebo for 2 weeks (Trial 1), or DNK333 25 mg b.d. or placebo for 4 weeks (Trial 2). Primary efficacy variables studied were change from baseline of stool form at week 2, and satisfactory relief of IBS-related abdominal pain/discomfort and global IBS-D symptoms. Secondary efficacy variables, pharmacokinetics and safety were also evaluated. Results  In total, 315 subjects were randomised. There were no statistically significant differences between treatment groups for the primary efficacy variables. However, analysis of combined data from both trials revealed significant differences favouring DNK333 25 mg over placebo for satisfactory relief of IBS-related abdominal pain/discomfort and global IBS-D symptoms. Trends favouring improvement with DNK333 25 mg vs. placebo were seen for all secondary efficacy variables. DNK333 had a safety profile similar to placebo. Conclusions  DNK333 25 mg b.d. appears to be effective and well tolerated in women with IBS-D. Further studies with neurokinin antagonists are warranted.