Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 12-Week, Placebo-Controlled Phase 3 Trial (T3MPO-1)
William D Chey, Anthony J Lembo, David P Rosenbaum, William D Chey, Anthony J Lembo, David P Rosenbaum
Abstract
Objectives: 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).
Methods: 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.
Results: 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.
Discussion: 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.
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; 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: Medical writing support was provided by Svetha Sankar, BSc BVMS, and Steven Inglis, PhD, of Oxford PharmaGenesis and was funded by Ardelyx.
Potential competing interests: W.D.C. is a consultant for Allergan, Biomerica, IM Health, Ironwood, Outpost, Prometheus, QOL Medical, Ritter Pharmaceuticals, and Salix/Valeant and has received research funding from Ardelyx, Biomerica, Commonwealth Diagnostics International, Ironwood, Nestlé, QOL Medical, Salix/Valeant, Vibrant, and Zespri. A.J.L. is a consultant for Allergan, Ardelyx, Bioamerica, Ironwood, Prometheus, and Valeant and has received research funding from Prometheus, Bioamerica, Vibrant, and Ironwood. D.P.R. is an employee of, and has ownership interest in, Ardelyx, Inc.
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Source: PubMed