Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Aliment Pharmacol Ther. 2020 Jun;51(11):1139-1148. doi: 10.1111/apt.15711. Epub 2020 Apr 17.
Relamorelin, a pentapeptide ghrelin receptor agonist, accelerated gastric emptying significantly and improved symptoms in adults with diabetic gastroparesis in phase 2 trials.
To assess the safety and tolerability of relamorelin across phase 2 trials.
Safety assessments in patients aged 18-75 years (weight, adverse events [AEs] and laboratory tests) from two randomised, double-blind phase 2 trials (NCT01571297, NCT02357420; results published previously) were reviewed descriptively. Analysis of covariance assessed treatment effect on glycated haemoglobin (HbA1c) and blood glucose post hoc. Phase 2a and 2b trial durations were, respectively, 4 weeks (relamorelin 10 µg once or twice daily [b.d.] or placebo b.d.) and 12 weeks (relamorelin 10, 30 or 100 µg or placebo b.d.) with 1- and 2-week, single-blind placebo run-ins.
Among 204 phase 2a and 393 phase 2b patients, respectively, 67% and 62% were female, and 88% and 89% had type 2 diabetes. Proportions of patients reporting serious AEs were similar across treatment groups, as were those with ≥1 treatment-emergent AE (TEAE). TEAE-related discontinuations were proportionally higher in relamorelin groups than placebo. Of 12 serious TEAEs in phase 2a, none occurred in >1 patient. In phase 2b, five serious TEAEs were reported in >1 patient, and one (100 µg) died (urosepsis), all unrelated to relamorelin. In phase 2b, increased HbA1c and fasting blood glucose levels were dose-related (P < 0.0001 and P = 0.0043, respectively).
Relamorelin showed acceptable safety and tolerability in phase 2 trials. Relamorelin may elevate blood glucose: this should be managed proactively in relamorelin-treated patients.
雷拉莫林是一种五肽促胃液素受体激动剂，在 2 期临床试验中显著加速了胃排空，并改善了糖尿病胃轻瘫成人的症状。
评估雷拉莫林在 2 期临床试验中的安全性和耐受性。
对来自两项随机、双盲 2 期临床试验（NCT01571297、NCT02357420；先前已发表结果）的年龄在 18-75 岁的患者（体重、不良事件[AE]和实验室检查）进行安全性评估。协方差分析评估了治疗对糖化血红蛋白（HbA1c）和血糖的影响。2a 期和 2b 期的试验持续时间分别为 4 周（雷拉莫林 10μg，每日一次或两次[b.d.]或安慰剂 b.d.）和 12 周（雷拉莫林 10、30 或 100μg或安慰剂 b.d.），各有 1 周和 2 周的单盲安慰剂导入期。
在分别纳入 204 例 2a 期和 393 例 2b 期患者中，67%和 62%为女性，88%和 89%患有 2 型糖尿病。治疗组报告严重不良事件的比例相似，治疗相关不良事件的比例也相似。与安慰剂相比，雷拉莫林组的治疗相关停药比例更高。在 2a 期的 12 例严重治疗相关不良事件中，没有 1 例发生在 1 例以上患者中。在 2b 期，有 5 例严重治疗相关不良事件发生在 1 例以上患者中，1 例（100μg）死亡（菌血症），均与雷拉莫林无关。在 2b 期，HbA1c 和空腹血糖水平的升高与剂量相关（P<0.0001 和 P=0.0043）。
雷拉莫林在 2 期临床试验中表现出可接受的安全性和耐受性。雷拉莫林可能会升高血糖：在接受雷拉莫林治疗的患者中，应积极管理血糖。
