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