Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Great Lakes Gastroenterology, Mentor, Ohio, USA.
Neurogastroenterol Motil. 2023 Nov;35(11):e14658. doi: 10.1111/nmo.14658. Epub 2023 Sep 5.
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.
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.
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.
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.
Tenapanor 是一种首创的、对肠道钠/氢交换体 3 型（NHE3）具有最小系统抑制作用的药物，基于两项随机、安慰剂对照、三期研究（T3MPO-1[NCT02621892]，T3MPO-2[NCT02686138]），被批准用于治疗成人肠易激综合征伴便秘（IBS-C）。开放标签 T3MPO-3 扩展研究（NCT02727751）纳入了完成这些研究的患者，旨在研究 tenapanor 的长期安全性和耐受性。
完成 T3MPO-1（16 周）或 T3MPO-2（26 周）的患者有资格参加 T3MPO-3。T3MPO-3 中的患者接受开放标签 tenapanor 50mg，每日两次，最多再治疗 39（T3MPO-1）或 26（T3MPO-2）周。治疗中出现的不良事件（TEAEs）在整个 T3MPO-3 安全性人群和接受了总共≥52 周 tenapanor 治疗的患者中进行评估。
共有 312 名患者入组 T3MPO-3；90 名患者接受了≥52 周的 tenapanor 治疗。安全性人群中有 117（37.5%）名患者和接受了≥52 周 tenapanor 治疗的 52（57.8%）名患者报告了 TEAEs。腹泻是最常见的 TEAEs，在安全性人群中的发生率为 10.6%，在接受了≥52 周 tenapanor 治疗的患者中的发生率为 11.1%。大多数病例的严重程度为轻度或中度，安全性人群中仅报告了两例严重病例。在 T3MPO-3 研究期间没有死亡事件发生。
tenapanor 治疗≥52 周是可耐受的，安全性与短期研究相似。T3MPO 研究的综合结果表明，tenapanor 是 IBS-C 患者的一种有价值的新治疗选择。
