Efficacy of On-Demand Asimadoline, a Peripheral κ-Opioid Agonist, in Females With Irritable Bowel Syndrome

Background & Aims: In experimental animal models of irritable bowel syndrome (IBS) and human studies, peripheral κ opioid agonists have been shown to decrease sensation to colonic distention. The aim of this study was to compare the effects of the κ 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.