Tenapanor Treatment of Patients With Constipation‐Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo‐Controlled Efficacy and Safety Trial. (May 2017)

• Record Type: Journal Article
• Authors: Chey, William D; Lembo, Anthony J; Rosenbaum, David P
• Is Part Of: American journal of gastroenterology. Volume 112:Number 5(2017)
• Publication Date: 2017-05
• Subjects: Stomach -- Diseases -- Periodicals; Intestines -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Gastrointestinal Diseases -- Periodicals; Electronic journals; Periodicals; 616.33
• DOI: 10.1038/ajg.2017.41
• Languages: English
• ISSNs: 0002-9270

Abstract

Abstract : Objectives: Tenapanor is a first‐in‐class, small‐molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger NHE3. This study assessed the efficacy and safety of tenapanor in patients with constipation‐predominant irritable bowel syndrome (IBS‐C). Methods: In this phase 2, double‐blind study, patients with IBS‐C (Rome III criteria) were randomized (1:1:1:1) to receive tenapanor 5 mg, 20 mg, or 50 mg b.i.d., or placebo b.i.d. for 12 weeks. The primary end point was the complete spontaneous bowel movement (CSBM) responder rate, defined as the proportion of patients reporting an increase from baseline of ≥1 CSBM/week for ≥6/12 treatment weeks. Secondary end points included abdominal symptom responder rates (≥30% score improvement from baseline for ≥6/12 weeks) and a composite responder rate (CSBM and abdominal pain response in the same week for ≥6/12 weeks). Results: Overall, 356 patients were randomized (mean age: 45.7 years; 86.8% women) and 304 completed the study. The CSBM responder rate was significantly higher in the tenapanor 50 mg b.i.d. group than in the placebo group (60.7 vs. 33.7%; P <0.001), as was the composite responder rate (50.0 vs. 23.6%; P <0.001). Responder rates for abdominal symptoms (pain, discomfort, bloating, cramping, and fullness) were significantly higher in the tenapanor 50 mg b.i.d. group than in the placebo group (all P <0.05). Diarrhea was the most frequent adverse event (tenapanor b.i.d.: 20 mg, 12.4%; 50 mg, 11.2%). Conclusions: Tenapanor 50 mg b.i.d. significantly increased stool frequency and reduced abdominal symptoms in patients with IBS‐C. Further research into tenapanor as a potential treatment for these patients is justified.