Long‐term safety of tenapanor in patients with irritable bowel syndrome with constipation in the T3MPO‐3 study.

Background: Tenapanor, a first‐in‐class, minimally systemic inhibitor of intestinal sodium/hydrogen exchanger isoform 3 (NHE3), is approved for the treatment of irritable bowel syndrome with constipation (IBS‐C) in adults based on two randomized, placebo‐controlled, phase III studies (T3MPO‐1 [NCT02621892], T3MPO‐2 [NCT02686138]). The open‐label T3MPO‐3 extension study (NCT02727751) enrolled patients who completed these studies to investigate long‐term safety and tolerability of tenapanor. Methods: Patients who completed T3MPO‐1 (16 weeks) or T3MPO‐2 (26 weeks) were eligible for enrollment in T3MPO‐3. Patients in T3MPO‐3 received open‐label tenapanor 50 mg twice a day for up to an additional 39 (T3MPO‐1) or 26 (T3MPO‐2) weeks. Treatment‐emergent adverse events (TEAEs) were evaluated in the entire T3MPO‐3 safety population and in patients who received a total of ≥52 weeks of tenapanor. Key Results: A total of 312 patients were enrolled in T3MPO‐3; 90 received ≥52 weeks of tenapanor. TEAEs were reported in 117 (37.5%) patients in the safety population and in 52 (57.8%) patients who received ≥52 weeks of tenapanor. Diarrhea was the most common TEAE, occurring in 10.6% of the safety population and in 11.1% of patients who received ≥52 weeks of tenapanor. Most cases were mild or moderate in severity, with only two severe cases reported in the safety population. No deaths occurred during the T3MPO‐3 study. Conclusions: Tenapanor was tolerable over ≥52 weeks of treatment and showed similar safety to that seen in shorter studies. Combined results of the T3MPO studies indicate that tenapanor is a valuable new treatment option for patients with IBS‐C. [ABSTRACT FROM AUTHOR]