Su1379 Using the FDA Composite Endpoint for IBS-D to Compare Treatment Effectiveness of Existing and Investigational Therapeutic Options

Abstract

Introduction Ibodutant, a selective and potent antagonist of neurokinin 2 receptors under clinical development for Irritable Bowel Syndrome with Diarrhea (IBS-D). A phase II (IRIS 2) study tested the efficacy of 8-week oral treatment with 3 doses of ibotudant in a total 559 IBS-D patients defined by Rome III criteria. Based on the combined response of satisfactory relief of IBS symptoms and abdominal pain/discomfort according to the 75% rule, i.e. positive response in at least 6 out of 8 treatment weeks (primary end-point), a statistically and clinically relevant efficacy was demonstrated in the female subgroup (n=333) at the 10 mg dose with 46.84% of responders vs 24.36% in placebo (p=0.0034). Aim To evaluate the benefit of ibodutant in the female population exposed to the efficacious oral daily dose of 10 mg participating to the IRIS 2 study when considering the mean abdominal pain severity score at baseline. Methods The analysis of primary efficacy end-point was repeated classifying female patients according to the mean abdominal pain score at baseline, as recorded on the daily diary during the 2 week no-treatment run-in phase, with pain rating on a 0-4 scale (0= no pain; 4= very severe). Two severity categories were considered, with mean score > 2 defining patients with severe/very severe pain. Results At baseline, n= 228 female patients (40.79% of total patients) reported severe/very severe mean abdominal pain score. In this population, ibodutant 10 mg confirmed the high clinically and statistically significant superiority to placebo in terms of reaching satisfactory relief of overall IBS symptoms and abdominal pain/discomfort, with a response rate of 47.06% versus 21.05% (p=0.0044). The same magnitude of responders (46.43%) was shown in patients reporting mild /moderate abdominal pain score at baseline, however responders to placebo was consistently higher (33.3%), and the difference did not reach statistical significance. Conclusion When the severity criteria of IBS-D patients are established according to the abdominal pain at baseline, ibodutant confirmed a significant benefit at 10 mg once daily dose in the severe/very severe female population. The analysis also showed patients with lower pain intensity are characterized by a significantly higher placebo response.