Abstract：
Previous clinical studies of trazpiroben, a dopamine D2 /D3 receptor antagonist for long-term treatment of moderate-to-severe idiopathic and diabetic gastroparesis, have shown improved symptoms of fullness. This study assessed trazpiroben efficacy, safety, and tolerability in adults with idiopathic and diabetic gastroparesis versus placebo.
This global, multicenter, double-blind, parallel-group, phase 2b study (NCT03544229) enrolled eligible adults aged 18-85 years with symptomatic idiopathic or diabetic gastroparesis. Randomized participants received either oral placebo or trazpiroben 5, 25, or 50 mg, administered twice daily over 12 weeks, and completed the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary. Change in weekly composite score from baseline to week 12 (primary endpoint) and treatment-emergent adverse events were assessed. Data were summarized descriptively.
Overall, 242 participants were enrolled (mean [standard deviation] age 55.7 [14.2] years; 75.6% female); 193 completed the study. No significant differences in change from baseline in weekly average of the daily diary composite score occurred at week 12 between placebo (least-squares mean [standard error] -1.19 [0.12]) and trazpiroben (5, 25, and 50 mg: -1.11 [0.22], -1.17 [0.12], and -1.21 [0.12], respectively). Overall, 41.4% of participants receiving trazpiroben reported treatment-emergent adverse events (placebo, 39.7%). No serious events were considered trazpiroben-related; no life-threatening or fatal events were reported.
There was no clinically meaningful difference in efficacy between trazpiroben and placebo in treating gastroparesis, based on the primary endpoint analysis. Trazpiroben was well tolerated with no new safety concerns identified, strengthening evidence supporting its favorable safety profile. NCT number: NCT03544229.
This global, multicenter, double-blind, parallel-group, phase 2b study (NCT03544229) enrolled eligible adults aged 18-85 years with symptomatic idiopathic or diabetic gastroparesis. Randomized participants received either oral placebo or trazpiroben 5, 25, or 50 mg, administered twice daily over 12 weeks, and completed the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary. Change in weekly composite score from baseline to week 12 (primary endpoint) and treatment-emergent adverse events were assessed. Data were summarized descriptively.
Overall, 242 participants were enrolled (mean [standard deviation] age 55.7 [14.2] years; 75.6% female); 193 completed the study. No significant differences in change from baseline in weekly average of the daily diary composite score occurred at week 12 between placebo (least-squares mean [standard error] -1.19 [0.12]) and trazpiroben (5, 25, and 50 mg: -1.11 [0.22], -1.17 [0.12], and -1.21 [0.12], respectively). Overall, 41.4% of participants receiving trazpiroben reported treatment-emergent adverse events (placebo, 39.7%). No serious events were considered trazpiroben-related; no life-threatening or fatal events were reported.
There was no clinically meaningful difference in efficacy between trazpiroben and placebo in treating gastroparesis, based on the primary endpoint analysis. Trazpiroben was well tolerated with no new safety concerns identified, strengthening evidence supporting its favorable safety profile. NCT number: NCT03544229.
摘要：
背景：先前对曲吡罗本的临床研究，多巴胺D2/D3受体拮抗剂用于长期治疗中度至重度特发性和糖尿病性胃轻瘫，表现出改善的饱腹症状。这项研究评估了曲匹本的疗效，安全,成人特发性和糖尿病性胃轻瘫与安慰剂的耐受性。
方法：这个全球性的，多中心，双盲,平行组，2b期研究(NCT03544229)纳入了18~85岁有症状的特发性或糖尿病性胃轻瘫患者.随机参与者接受口服安慰剂或曲吡罗本5、25或50mg，每天两次，超过12周，并完成了美国神经胃肠病学和动力学会胃轻瘫的症状指数-每日日记。评估从基线到第12周（主要终点）的每周综合评分的变化以及治疗引起的不良事件。数据进行了描述性总结。
结果：总体而言，242名参与者入组（平均[标准差]年龄55.7[14.2]岁；75.6%为女性）；193人完成研究。安慰剂（最小二乘平均值[标准误差]-1.19[0.12]）和曲匹罗本（5、25和50mg：-1.11[0.22]，-1.17[0.12]，和-1.21[0.12]，分别)。总的来说,41.4％的接受曲兹匹罗本的参与者报告了因治疗引起的不良事件（安慰剂，39.7%）。没有严重事件被认为是与曲兹匹本相关的；没有报告危及生命或致命的事件。
结论：曲匹本和安慰剂治疗胃轻瘫的疗效没有临床意义的差异，基于主要终点分析。Trazpiroben的耐受性良好，没有发现新的安全问题，加强证据支持其有利的安全性。NCT编号：NCT03544229。
方法：这个全球性的，多中心，双盲,平行组，2b期研究(NCT03544229)纳入了18~85岁有症状的特发性或糖尿病性胃轻瘫患者.随机参与者接受口服安慰剂或曲吡罗本5、25或50mg，每天两次，超过12周，并完成了美国神经胃肠病学和动力学会胃轻瘫的症状指数-每日日记。评估从基线到第12周（主要终点）的每周综合评分的变化以及治疗引起的不良事件。数据进行了描述性总结。
结果：总体而言，242名参与者入组（平均[标准差]年龄55.7[14.2]岁；75.6%为女性）；193人完成研究。安慰剂（最小二乘平均值[标准误差]-1.19[0.12]）和曲匹罗本（5、25和50mg：-1.11[0.22]，-1.17[0.12]，和-1.21[0.12]，分别)。总的来说,41.4％的接受曲兹匹罗本的参与者报告了因治疗引起的不良事件（安慰剂，39.7%）。没有严重事件被认为是与曲兹匹本相关的；没有报告危及生命或致命的事件。
结论：曲匹本和安慰剂治疗胃轻瘫的疗效没有临床意义的差异，基于主要终点分析。Trazpiroben的耐受性良好，没有发现新的安全问题，加强证据支持其有利的安全性。NCT编号：NCT03544229。
