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

BackgroundTenapanor, 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.MethodsPatients 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 ResultsA 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.ConclusionsTenapanor 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.