Background  In models of irritable bowel syndrome (IBS), asimadoline, a kappa‐opioid agonist, improves pain and abnormal bowel function.

Aim  To evaluate the effects of three doses of asimadoline and placebo in subjects with IBS through a double‐blind, randomized, placebo‐controlled trial.

Methods  Patients were randomly assigned to receive asimadoline 0.15, 0.5, 1.0 mg or placebo BID for 12 weeks. The primary efficacy measure was number of months of adequate relief of IBS pain or discomfort, with a prospective plan to evaluate adequate relief data by entry baseline pain and subtype. Several other endpoints were also evaluated.

Results  Five hundred and ninety‐six patients were randomized. In the ITT population, statistically significant improvement on the primary endpoint was not seen. However, in diarrhoea‐predominant IBS patients with at least baseline moderate pain, asimadoline (0.5 mg) produced significant improvement on total number of months with adequate relief of IBS pain or discomfort (46.7% vs. 20.0%), adequate relief of IBS symptoms (46.7% vs. 23.0%), pain scores (week 12: −1.6 vs. −0.7), pain free days (42.9% vs. 18.0%), urgency and stool frequency (−2.3 vs. −0.3). In patients with alternating IBS, significant improvement was seen on adequate relief endpoints. Asimadoline was well tolerated.

Conclusion  Asimadoline warrants further evaluation as a treatment for IBS.