Efficacy and safety of vibegron for the treatment of irritable bowel syndrome in women: Results of a randomized, double-blind, placebo-controlled phase 2 trial.

BACKGROUND

Preclinical and clinical studies suggest that β3 -adrenergic receptor activation may be a novel target for treating abdominal pain and gastrointestinal motility dysfunction in patients with irritable bowel syndrome (IBS). This proof-of-concept study evaluated the efficacy and safety of the β3 -adrenergic agonist vibegron in treating IBS-related pain.

METHODS

Adult women with predominant-diarrhea IBS (IBS-D) or with mixed diarrhea/constipation (IBS-M), diagnosed using Rome IV criteria, were randomized 1:1 to receive once-daily vibegron 75 mg or placebo for 12 weeks. The primary endpoint was the percentage of patients with IBS-D considered abdominal pain intensity (API) weekly responders, defined as ≥30% reduction from baseline at week 12 in mean weekly worst abdominal pain over 24 hours using the API score. Patients completed a pain diary at baseline and at weeks 2, 4, 8, and 12. Safety was assessed by adverse events (AEs) in the overall IBS population.

KEY

RESULTS

Of the 222 patients with IBS randomized (vibegron, N = 111; placebo, N = 111), 85% completed the trial. There was no significant difference in the percentage of patients with IBS-D (vibegron, N = 66; placebo, N = 63) considered API weekly responders with vibegron vs. placebo (p = 0.8222) after 12 weeks. The incidence of AEs was comparable between treatment groups (33.3% each), with equal rates of worsening IBS symptoms (2.7% each).

CONCLUSIONS AND INFERENCES: In women with IBS-D, vibegron was not associated with significant improvement in the percentage of API weekly responders. Vibegron was generally safe and well tolerated and, in particular, did not worsen IBS symptoms vs. placebo.