ORP-101 for IBS with diarrhoea misses mark in phase II trial

The novel partial μ receptor agonist and full κ receptor antagonist ORP-101 has failed to demonstrate superiority to placebo in the treatment of patients with irritable bowel syndrome (IBS) with diarrhoea (IBS-D) in a phase II randomized controlled trial.

A total of 320 patients with IBS-D participated in the trial. These patients were randomly assigned to receive treatment with ORP-101 at 50 mg (n=65) or 100 mg (n=127) or placebo (n=128). Treatment was administered once daily for 12 weeks. The 50-mg ORP-101 dose was discontinued after interim analysis as part of the adaptive design.

The primary endpoint of treatment response was a composite of improvement in abdominal pain (30-percent improvement from baseline) and stool consistency (average daily stool consistency <5 on the Bristol Stool Form Scale, or 30-percent improvement in abdominal pain if no bowel movement) for 50 percent of days over the 12-week treatment period.

The percentage of patients who showed treatment response did not significantly differ across the three treatment groups: 16.9 percent with ORP-101 50 mg, 28.3 percent with ORP-101 100 mg, and 21.9 percent with placebo (p=0.79 for the three groups and p=0.12 for ORP-101 100 mg vs placebo).

Results for multiple secondary and exploratory endpoints favoured ORP-101 100 mg vs placebo.  

In terms of safety, ORP-101 was well tolerated, including in patients without gallbladders.

Researchers shared that ORP-101 will be explored in other chronic pain conditions in future studies.