Journal Article

Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1)

Lembo, Anthony J., Chey, William D., Rosenbaum, David P.

2020

Overview

Tenapanor is a first-in-class, minimally absorbed, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3. This phase 3 trial assessed the efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C). In this phase 3, double-blind study (ClinicalTrials.gov identifier NCT02621892), patients with IBS-C were randomized to tenapanor 50 mg b.i.d. or placebo b.i.d. for 12 weeks followed by a 4-week randomized withdrawal period. The primary efficacy variable was the proportion of patients who reported a reduction in average weekly worst abdominal pain of ≥30.0% and an increase of ≥1 complete spontaneous bowel movement from baseline, both in the same week, for ≥6 weeks of the 12-week treatment period. Of the 629 randomized patients with IBS-C, 606 (96.3%) were included in the intention-to-treat analysis set (tenapanor: n = 307; placebo: n = 299) and 533 (84.7%) completed the 12-week treatment period. In the intention-to-treat analysis set (mean age 45 years, 81.4% women), a significantly greater proportion of patients treated with tenapanor met the primary endpoint than patients treated with placebo (27.0% vs 18.7%, P = 0.020). Abdominal symptoms and global symptoms of IBS also improved with tenapanor (P < 0.05 vs placebo). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in 6.5% and 0.7% of patients receiving tenapanor and placebo, respectively, during the 12-week treatment period. Tenapanor 50 mg b.i.d. improved IBS-C symptoms and was generally well tolerated, offering a potential new treatment option for patients with IBS-C.

• Publisher: Wolters Kluwer,Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subject: Abdomen / Abdominal Pain - etiology / Abdominal Pain - physiopathology / Accountability / Adult / Chloride / Colonoscopy / Constipation / Constipation - drug therapy / Constipation - etiology / Constipation - physiopathology / Deprescriptions / Diarrhea - chemically induced / Double-Blind Method / Female / Functional GI Disorders / Gastroenterology / Humans / Irritable bowel syndrome / Irritable Bowel Syndrome - complications / Irritable Bowel Syndrome - drug therapy / Irritable Bowel Syndrome - physiopathology / Isoquinolines - therapeutic use / Male / Middle Aged / Pain / Patients / Sodium-Hydrogen Exchanger 3 - antagonists & inhibitors / Sulfonamides - therapeutic use / Treatment Outcome / Variables