OBJECTIVES Tenapanor is a first-in-class, minimally absorbed, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3. This phase 3 trial assessed the efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with constipation-predominant irritable bowel syndrome (IBS-C). METHODS In this phase 3, double-blind study (ClinicalTrials.gov identifier NCT02621892), patients with IBS-C were randomized to tenapanor 50 mg b.i.d. or placebo b.i.d. for 12 weeks followed by a 4-week randomized withdrawal period. The primary efficacy variable was the proportion of patients who reported a reduction in average weekly worst abdominal pain of ≥30.0% and an increase of ≥1 complete spontaneous bowel movement from baseline, both in the same week, for ≥6 weeks of the 12-week treatment period. RESULTS Of the 629 randomized patients with IBS-C, 606 (96.3%) were included in the intention-to-treat analysis set (tenapanor: n = 307; placebo: n = 299) and 533 (84.7%) completed the 12-week treatment period. In the intention-to-treat analysis set (mean age 45 years, 81.4% women), a significantly greater proportion of patients treated with tenapanor met the primary endpoint than patients treated with placebo (27.0% vs 18.7%, P = 0.020). Abdominal symptoms and global symptoms of IBS also improved with tenapanor (P < 0.05 vs placebo). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in 6.5% and 0.7% of patients receiving tenapanor and placebo, respectively, during the 12-week treatment period. DISCUSSION Tenapanor 50 mg b.i.d. improved IBS-C symptoms and was generally well tolerated, offering a potential new treatment option for patients with IBS-C.

中文翻译：

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Tenapanor 治疗便秘型肠易激综合征患者的疗效：一项为期 12 周的安慰剂对照 3 期试验 (T3MPO-1)。

目标 Tenapanor 是一种一流的、吸收最小的、胃肠道钠/氢交换异构体 3 的小分子抑制剂。该 3 期试验评估了 50 mg 每天两次的 Tenapanor 治疗便秘型患者的疗效和安全性肠易激综合征（IBS-C）。方法 在这项 3 期双盲研究（ClinicalTrials.gov 标识符 NCT02621892）中，IBS-C 患者被随机分配到tenapanor 50 mg bid 或安慰剂 bid 治疗 12 周，然后是 4 周的随机停药期。主要疗效变量是报告平均每周最严重腹痛减少 ≥ 30.0% 和增加 ≥ 1 次完全自发排便的患者比例，均在同一周内，持续 12-6 周。周治疗期。结果 在 629 名 IBS-C 随机患者中，606 名（96.3%）被纳入意向治疗分析组（tenapanor：n = 307；安慰剂：n = 299），533 名（84.7%）完成了 12-周治疗期。在意向治疗分析组（平均年龄 45 岁，81.4% 的女性）中，与接受安慰剂治疗的患者相比，接受 Tenapanor 治疗的患者达到主要终点的比例显着高于接受安慰剂治疗的患者（27.0% vs 18.7%，P = 0.020）。替那帕诺也改善了 IBS 的腹部症状和整体症状（与安慰剂相比，P < 0.05）。腹泻是最常报告的不良事件，在 12 周的治疗期间，分别有 6.5% 和 0.7% 的接受替那帕诺和安慰剂的患者停止研究药物。讨论 Tenapanor 50 mg bid 改善了 IBS-C 症状并且一般耐受性良好，