Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2)
William D Chey, Anthony J Lembo, Yang Yang, David P Rosenbaum, William D Chey, Anthony J Lembo, Yang Yang, David P Rosenbaum
Abstract
Introduction: 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 long-term efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with irritable bowel syndrome with constipation (IBS-C).
Methods: In this randomized double-blind study (ClinicalTrials.gov identifier: NCT02686138), patients with IBS-C received tenapanor 50 mg b.i.d. or placebo b.i.d. for 26 weeks. The primary endpoint was the proportion of patients who had a reduction of ≥30.0% in average weekly worst abdominal pain and an increase of ≥1 weekly complete spontaneous bowel movement from baseline, both in the same week, for ≥6 of the first 12 treatment weeks (6/12-week combined responder).
Results: Of the 620 randomized patients with IBS-C, 593 (95.6%) were included in the intention-to-treat analysis set (tenapanor: n = 293; placebo: n = 300) and 481 patients (77.6%) completed the 26-week treatment period. In the intention-to-treat analysis set (mean age: 45.4 years; 82.1% women), a significantly greater proportion of patients treated with tenapanor were 6/12-week combined responders than those treated with placebo (36.5% vs 23.7%; P < 0.001). Abdominal symptoms and global symptoms of IBS were significantly improved with tenapanor compared with placebo. Diarrhea, the most common adverse event, was typically transient and mild to moderate in severity. Diarrhea led to study drug discontinuation for 19 (6.5%) and 2 patients (0.7%) receiving tenapanor and placebo, respectively.
Discussion: Tenapanor 50 mg b.i.d. improved IBS-C symptoms over 26 weeks and was generally well tolerated, offering a potential new long-term treatment option for patients with IBS-C (see Visual abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B797).
Trial registration: ClinicalTrials.gov NCT02621892 NCT02686138 NCT02727751.
Conflict of interest statement
Guarantor of the article: William D. Chey, MD, AGAF, FACG, FACP, RFF.
Specific author contributions: W.D.C. and A.J.L.: contributed to the planning of the study, interpretation of the data, and critical revision of the manuscript for important intellectual content. Y.Y.: reviewed the manuscript critically for statistical content and contributed to the interpretation of the data and critical revision of the manuscript for important intellectual content. D.P.R.: contributed to the planning of the study, conduct of the study, interpretation of the data, and critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript for submission.
Financial support: Ardelyx was the sponsor of the study.
Potential competing interests: W.D.C. is a consultant for Allergan, Biomerica, IM Health, Humphries Pharmaceuticals, Ironwood Pharmaceuticals, Phathom, QOL Medical, Ritter Pharmaceuticals, Salix/Valeant, and Urovant and has received research funding from Biomerica, Commonwealth Diagnostics International, QOL Medical, Salix/Valeant, Vibrant, and Zespri. A.J.L. is a consultant for Allergan, Ardelyx, Biomerica, Ironwood Pharmaceuticals, Prometheus Laboratories, and Valeant and has received research funding from Prometheus Laboratories, Biomerica, Vibrant, and Ironwood Pharmaceuticals. Y.Y. is an employee of Ardelyx. D.P.R. is an employee of and has an ownership interest in Ardelyx.
ClinicalTrials.gov identifier: NCT02686138.
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
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Source: PubMed