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 bid, or placebo bid 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 bid 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 bid group than in the placebo group (allP< 0.05). Diarrhea was the most frequent adverse event (tenapanor bid: 20 mg, 12.4%; 50 mg, 11.2%).

Conclusions:

Tenapanor 50 mg bid 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.