Apraglutide, a novel glucagon-like peptide-2 analog, improves fluid absorption in patients with short bowel syndrome intestinal failure: Findings from a placebo-controlled, randomized phase 2 trial.
Apraglutide, a novel glucagon-like peptide-2 analog, improves fluid absorption in patients with short bowel syndrome intestinal failure: Findings from a placebo-controlled, randomized phase 2 trial.
复制标题
DOI：
10.1002/jpen.2223
复制
发表时间：
2022-05
影响因子：
3.4
通讯作者：
Jeppesen, Palle B.
中科院分区：
文献类型：
--
作者：
Eliasson, Johanna;Hvistendahl, Mark K.;Freund, Nanna;Bolognani, Federico;Meyer, Christian;Jeppesen, Palle B.
关键词：
胰高血糖素样肽-2 (GLP-2) 类似物治疗可改善短肠综合征相关肠衰竭 (SBS-IF) 患者的肠道适应，并可能减少肠外支持需求。阿普拉鲁肽是一种新型长效 GLP-2 类似物，设计为每周一次给药。该试验研究了阿普拉鲁肽治疗 SBS-IF 患者的安全性和有效性。在这项安慰剂对照、双盲、随机、交叉 2 期试验中，8 名 SBS-IF 成人接受每周一次 5 mg 阿普拉鲁肽和安慰剂治疗 4 周，然后每周一次 10 mg 阿普拉鲁肽治疗 4 周，治疗之间有 6-10 周的清除期。安全性是主要终点。次要终点包括与安慰剂相比，在每个治疗期之前和之后 48 小时收集的尿量输出量相对于基线的变化。常见的治疗相关不良事件（AE）为轻度至中度，包括多尿、造口排量减少、造口并发症、口渴减少和水肿。没有严重的 AE 被认为与阿普拉鲁肽治疗相关。较低剂量和较高剂量的安全性相当。与安慰剂相比，每周一次 5 毫克和 10 毫克阿普拉鲁肽治疗显着增加尿量，调整后平均值分别为 714 毫升/天（95% CI，490-939；P < .05）和 795 毫升/天（95% CI，195-1394；P < .05），剂量之间没有显着差异。每周一次的阿普拉鲁肽在两种测试剂量下均具有良好的耐受性，并显着增加尿量，为肠液吸收增加提供了证据。一项针对成人 SBS-IF 的 3 期试验正在进行中。
Treatment with glucagon‐like peptide‐2 (GLP‐2) analogs improve intestinal adaptation in patients with short bowel syndrome–associated intestinal failure (SBS‐IF) and may reduce parenteral support requirements. Apraglutide is a novel, long‐acting GLP‐2 analog designed for once‐weekly dosing. This trial investigated the safety and efficacy of apraglutide in patients with SBS‐IF. In this placebo‐controlled, double‐blind, randomized, crossover phase 2 trial, eight adults with SBS‐IF were treated with once‐weekly 5‐mg apraglutide doses and placebo for 4 weeks, followed by once‐weekly 10‐mg apraglutide doses for 4 weeks, with a washout period of 6–10 weeks between treatments. Safety was the primary end point. Secondary end points included changes from baseline in urine volume output compared with placebo, collected for 48 h before and after each treatment period. Common treatment‐related adverse events (AEs) were mild to moderate and included polyuria, decreased stoma output, stoma complications, decreased thirst, and edema. No serious AEs were considered to be related to apraglutide treatment. The safety profile was comparable for the lower and higher doses. Treatment with once‐weekly 5‐ and 10‐mg apraglutide doses significantly increased urine volume output by an adjusted mean of 714 ml/day (95% CI, 490–939; P < .05) and 795 ml/day (95% CI, 195–1394; P < .05), respectively, compared with placebo, with no significant differences between doses. Once‐weekly apraglutide was well tolerated at both tested doses and significantly increased urine volume output, providing evidence for increased intestinal fluid absorption. A phase 3 trial is underway in adults with SBS‐IF.
登录
查看更多内容
影响因子：
--
作者：
Bremholm, Lasse;Hornum, Mads;Jeppesen, Palle Bekker
通讯作者：
Jeppesen, Palle Bekker
影响因子：
24.5
作者：
Cani PD;Possemiers S;Van de Wiele T;Guiot Y;Everard A;Rottier O;Geurts L;Naslain D;Neyrinck A;Lambert DM;Muccioli GG;Delzenne NM
通讯作者：
Delzenne NM
影响因子：
24.5
作者：
Jeppesen PB;Gilroy R;Pertkiewicz M;Allard JP;Messing B;O'Keefe SJ
通讯作者：
O'Keefe SJ
影响因子：
2
作者：
Jeppesen PB;Lund P;Gottschalck IB;Nielsen HB;Holst JJ;Mortensen J;Poulsen SS;Quistorff B;Mortensen PB
通讯作者：
Mortensen PB
影响因子：
24.5
作者：
Jeppesen, PB;Hartmann, B;Mortensen, PB
通讯作者：
Mortensen, PB