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Tenapanor improves global endpoints in IBS-C
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LAS VEGAS — Tenapanor at a dose of 50 mg twice per day significantly improved global endpoints in constipation-predominant irritable bowel syndrome, according to phase 2b trial data presented at ACG 2016.
“Sodium/hydrogen exchanger isoform 3, or NHE3, is the major absorptive sodium hydrogen exchanger in the gut,” William D. Chey, MD, from the division of gastroenterology at University of Michigan, Ann Arbor, said during his presentation. “Tenapanor [Ardelyx] is a first-in-class, minimally systemic small molecule which inhibits NHE3. This compound is specific for NHE3 and it reduces absorption of dietary sodium and phosphate in preclinical and clinical studies, and thus there’s potential that this may offer benefits for patients with IBS-C.”
William D. Chey
In a double blind fashion, Chey and colleagues randomly assigned 356 patients with IBS-C (mean age, 45.7 years; 87% women; 76% white) to receive 5 mg, 20 mg or 50 mg tenapanor or placebo orally twice daily for 12 weeks.
“This was a fairly severely affected group,” Chey said, with an average of 0.2 complete spontaneous bowel movements (CSBMs) per week, two spontaneous bowel movements (SBMs) per week, Bristol Stool Form Scale scores of 1.8 and abdominal pain scores of 6.1 out of 10 during the 2-week baseline period.
The CSBM responder rate served as the primary endpoint, which is defined by the FDA as the proportion of patients with an increase of at least one CSBM per week for at least 6 of the 12 treatment weeks. Abdominal pain responder rate, defined as the proportion of patients with at least a 30% decrease in abdominal pain for at least 6 of the treatment weeks, and the overall responder rate, requiring responses in both CSBM and abdominal pain for at least 6 of the treatment weeks, served as secondary endpoints.
The main results, which were previously presented at DDW, included a primary CSBM responder rate of about 61% with 50 mg tenapanor vs. 50% with placebo, an abdominal pain responder score of 66% vs. 48%, and an overall responder rate of 50% vs. 23.6%.
Symptoms improved within the first week and benefits were sustained for the entire 12-week treatment period.
“The lower doses did not provide as consistent benefits as the highest dose,” Chey said. “Global endpoints are important because … they are a lot easier for clinicians like myself to understand. They’re much easier to communicate a message in terms of clinical effectiveness as opposed to those FDA … endpoints, which … can be cumbersome and difficult to understand.”
These included adequate IBS symptom relief (63% vs. 39% with placebo; P = .002), IBS severity as measured by a 5-point scale (–1.35 vs. –1.03; P < .024), constipation severity as measured by a 5-point scale (–1.64 vs. –1.15; P < .001), degree of IBS symptom relief as measured by a 7-point scale (2.5 vs. 3.1; P < .001) and treatment satisfaction as measured by a 5-point scale (3.7 vs. 2.9; P < .001).
“In patients with IBS-C, treatment with tenapanor 50 mg twice daily produced statistically and clinically significant improvements in a variety of different endpoints,” Chey concluded. “The results of this phase 2b trial justify ongoing research in a phase 3 clinical program and that is indeed ongoing in the U.S. at the current time.” – by Adam Leitenberger
Reference:
Chey WD, et al. Abstract #64. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 17-19, 2016; Las Vegas, NV.
Disclosures: Chey reports he is a consultant for Albreio, Allergan, Ardelyx, IM Health, Ironwood, Nestle, Prometheus, QOL Medical, Salix, Syn Biologic and Takeda, and has received grant or research support from Ironwood, Nestle, Perrigo and Prometheus.