Tenapanor improved symptoms of irritable bowel syndrome with constipation (IBS-C) over 26 weeks compared with placebo and was generally well tolerated, according to a study in the American Journal of Gastroenterology.
This phase 3, randomized, double-blind, placebo-controlled study (T3MPO-2) enrolled patients with IBS-C from 92 centers in the United States from December 2015 to August 2017 (ClinicalTrials.gov Identifier: NCT02686138). Eligible participants were randomly assigned to receive either tenapanor hydrochloride 50 mg or placebo twice daily for 26 weeks. The 6/12-week combined responder rate, which was defined as the proportion of patients who had a weekly combined response for ≥6 of the first 12 weeks of treatment, was the primary endpoint.
Among the 620 patients who were randomly assigned to tenapanor or placebo, 593 participants were included in the intention-to-treat (ITT) and safety analysis sets, of whom 293 received tenapanor and 300 received placebo. The full 26-week treatment period was completed by 232 of the 306 patients (75.8%) who received tenapanor and by 249 of the 314 patients (79.3%) who received placebo. Participants in the ITT cohort had a mean age of 45.4 years, 82.1% were women, and 63.6% were White.
The investigators found that a significantly greater proportion of patients in the tenapanor group were 6/12-week combined responders compared with those in the placebo group (36.5% vs 23.7%; P <.001). The 6/12-week abdominal pain responder rate was also significantly higher among patients who received tenapanor vs those who received placebo (49.8% vs 38.3%; P =.004). In addition, a significantly greater proportion of patients in the tenapanor group were 6/12-week complete spontaneous bowel movement (CSBM) responders compared with those in the placebo group (47.4% vs 33.3%; P <.001).
A significantly greater proportion of patients in the tenapanor group were also 13/26-week combined responders compared with the placebo group (35.5% vs 24.3%; P =.003). Additionally, a significantly greater proportion of patients who received tenapanor compared with those who received placebo were 13/26-week abdominal pain responders (50.2% vs 40.0%; P =.013) as well as 13/26-week CSBM responders (41.3% vs 31.0%; P =.010).
Treatment-related adverse events were reported by 64 patients (21.8%) who received tenapanor and 28 patients (9.3%) who received placebo. Diarrhea was considered treatment related in 44 patients (15.0%) in the tenapanor group and in 8 patients (2.7%) in the placebo group, leading to drug discontinuation in 19 patients (6.5%) in the tenapanor group and in 2 patients (0.7%) in the placebo group.
Potential study limitations include use of the Rome III criteria, instead of the current Rome IV criteria, to identify patients for inclusion. The investigators also required that patients with IBS-C pass no more than 5 spontaneous bowel movements and fewer than 3 CSBMs per week to be eligible for randomization. Thus, the cohort may represent a more severely affected population than is encountered in routine clinical practice.
“The results from T3MPO-2, together with T3MPO-1, provided robust support for the recent FDA approval of tenapanor for the treatment of IBS-C,” stated the researchers. “Tenapanor is an effective and generally well tolerated new treatment option for patients with IBS-C,” they concluded.
Disclosure: The study was sponsored by Ardelyx. Some of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures.
Chey WD, Lembo AJ, Yang Y, Rosenbaum DP. Efficacy of tenapanor in treating patients with irritable bowel syndrome with constipation: a 26-week, placebo-controlled phase 3 trial (T3MPO-2). Am J Gastroenterol. 2021;116(6):1294-1303. doi:10.14309/ajg.0000000000001056