Efficacy of on-demand asimadoline, a peripheral kappa-opioid agonist, in females with irritable bowel syndrome.

Background & Aims: In experimental animal models of irritable bowel syndrome (IBS) and human studies, peripheral kappa opioid agonists have been shown to decrease sensation to colonic distention. The aim of this study was to compare the effects of the kappa opioid agonist, asimadoline, and placebo on episodes of abdominal pain in patients with IBS.

Methods: After a 2-week run-in period, 100 patients with IBS were randomized (3:2 ratio) to receive asimadoline, up to 1 mg 4 times daily, or placebo for 4 weeks in a double-blind study. Pain was scored by daily diary using a 100-mm visual analogue scale. During pain episodes, patients recorded the pain severity, took study medication, and recorded their pain score 2 hours later. The primary end point was the average reduction in pain severity 2 hours after treatment.

Results: The average pain reduction 2 hours posttreatment was not significantly different between the groups. Post hoc analyses suggest asimadoline was effective in mixed IBS (P = .003, unadjusted), but may be worse in diarrhea-predominant IBS (P = .065 unadjusted). The anxiety score was reduced modestly by asimadoline (P = .053). No significant adverse effects were noted.

Conclusions: An on-demand dosing schedule of asimadoline was not effective in reducing severity of abdominal pain in IBS. Further studies in visceral pain and IBS appear warranted.