E0264 - Potential of Tenapanor as a Treatment for Chronic Idiopathic Constipation (CIC): A Post Hoc Analysis From the T3MPO-1 and T3MPO-2 Phase 3 Studies for Irritable Bowel Syndrome With Constipation (IBS-C) in Adults

Introduction: Tenapanor is a first-in-class, minimally absorbed, small-molecule inhibitor of the intestinal sodium/hydrogen exchanger isoform 3 (NHE3), approved for the treatment of IBS-C in adults. Most recently ROME IV diagnostic criteria recognize that rather than being distinct entities functional constipation (FC) and IBS-C represent a continuum of symptoms. Wong, et al (AJG 2010) demonstrated that 89.5 % of patients meeting ROME III criteria for IBS-C also met the criteria for FC. Recognizing this overlap we performed a post hoc analysis, evaluating the efficacy of tenapanor for FC by utilizing the primary endpoint for chronic idiopathic constipation (CIC) in patients with IBS-C from the T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) phase 3 studies.

Am J Gastroenterol 2010; 105:2228–2234 Wong RK et al.

Methods: Adult patients with IBS-C (ROME III) with < 3 weekly complete spontaneous bowel movements (CSBM), ≤5 weekly spontaneous bowel movements (SBM) and weekly worst abdominal pain score ≥3 (0-10 numerical rating scale) during a 2-week screening period were randomized to tenapanor 50 mg or placebo twice a day. Data from the first 12 weeks of both trials was used to calculate the durable responder rate, which is the regulatory endpoint for CIC. A durable responder is a patient with a weekly increase of ≥1 CSBM from baseline and ≥3 CSBM per week for 9 of 12 weeks and 3 of the last 4 weeks of study.

Results: In the T3MPO-1 ITT population (tenapanor, n=307; placebo, n=299; mean age 45 years; 81% female), the responder rate vs placebo in durable responder rate was 11.28% (adjusted relative risk 3.35; p < 0.001). In the T3MPO-2 ITT population (tenapanor, n=293; placebo, n=300; mean age 45 years; 82% female), the responder rate vs placebo in durable responder rate was 15.49% (adjusted relative risk 3.75; p < 0.001).

Tenapanor was generally well tolerated. Diarrhea was the most common adverse event; severe diarrhea was reported in 2.5% of tenapanor-treated patients.

Discussion: Based on results from this post hoc analysis of the T3MPO-1 and T3MPO-2 Phase 3 studies for IBS-C in adults, tenapanor, with its novel mechanism of action, shows promise as a potential therapeutic option for CIC. Further clinical trials are needed to evaluate tenapanor for the CIC population to confirm these results.