Liraglutide in an Adolescent Population with Obesity: A Randomized, Double-Blind, Placebo-Controlled 5-Week Trial to Assess Safety, Tolerability, and Pharmacokinetics of Liraglutide in Adolescents Aged 12-17 Years
Liraglutide in an Adolescent Population with Obesity: A Randomized, Double-Blind, Placebo-Controlled 5-Week Trial to Assess Safety, Tolerability, and Pharmacokinetics of Liraglutide in Adolescents Aged 12-17 Years
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DOI：
10.1016/j.jpeds.2016.10.076
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发表时间：
2017-02-01
影响因子：
5.1
通讯作者：
Kordonouri, Olga
中科院分区：
文献类型：
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作者：
Danne, Thomas;Biester, Torben;Kordonouri, Olga
目的 研究利拉鲁肽在肥胖青少年中的安全性、耐受性和药代动力学。研究设计 这是一项随机、双盲、安慰剂对照试验。 21 名年龄 12-17 岁、Tanner 2-5 期肥胖受试者（体重指数 [BMI] 对应于年龄和性别的 BMI >= 95% 以及成人 BMI = 30 kg/m(2)；此外，BMI = 45 kg/m(2)）被随机（2:1）接受利拉鲁肽治疗 5 周（0.6 mg，每周剂量增加至最大）上周 3.0 mg）（n = 14）或安慰剂（n = 7）。主要终点是治疗中出现的不良事件（TEAE）的数量。次要终点包括安全性措施以及药代动力学和药效学终点。 结果 所有接受利拉鲁肽的参与者和 4 名接受安慰剂的参与者 (57.1%) 均至少有 1 次 TEAE。最常见的 TEAE 是胃肠道疾病。没有发生严重 TEAE、TEAE 相关戒断或死亡。接受利拉鲁肽的 8 名参与者和安慰剂组的 1 名参与者中发生了 12 次低血糖发作。没有严重低血糖事件的报道。利拉鲁肽的谷浓度暴露量随着剂量的增加而增加，尽管剂量比例因2.4 mg剂量时出人意料的低谷浓度值而受到干扰。稳态给药后 0 至 24 小时的模型衍生血浆浓度时间曲线下的暴露量与肥胖成人相似。 结论 当给肥胖青少年服用时，利拉鲁肽具有与成人相似的安全性和耐受性特征，没有意外的安全性/耐受性问题。结果表明，批准用于成人体重管理的给药方案可能适合青少年使用。
Objectives To investigate the safety, tolerability, and pharmacokinetics of liraglutide in adolescents with obesity.Study design This was a randomized, double-blind, placebo-controlled trial. Twenty-one subjects, aged 12-17 years and Tanner stage 2-5, with obesity (body mass index [BMI] corresponding to both a BMI >= 95th percentile for age and sex and to a BMI of = 30 kg/m(2) for adults; additionally, BMI was = 45 kg/m(2)) were randomized (2:1) to receive 5 weeks of treatment with liraglutide (0.6 mg with weekly dose increase to a maximum of 3.0 mg for the last week) (n = 14) or placebo (n = 7). The primary endpoint was number of treatment-emergent adverse events (TEAEs). Secondary endpoints included safety measures, and pharmacokinetic and pharmacodynamic endpoints.Results All participants receiving liraglutide, and 4 receiving placebo (57.1%), had at least 1 TEAE. The most common TEAEs were gastrointestinal disorders. No severe TEAEs, TEAE-related withdrawals, or deaths occurred. Twelve hypoglycemic episodes occurred in 8 participants receiving liraglutide and 2 in 1 participant receiving placebo. No severe hypoglycemic episodes were reported. Liraglutide exposure in terms of trough concentration increased with dose, although dose proportionality was confounded by unexpectedly low trough concentration values at the 2.4 mg dose. Exposure in terms of model-derived area under the plasma concentration time curve from 0 to 24 hours after dose in steady state was similar to that in adults with obesity.Conclusions Liraglutide had a similar safety and tolerability profile compared with adults when administered to adolescents with obesity, with no unexpected safety/tolerability issues. Results suggest that the dosing regimen approved for weight management in adults may be appropriate for use in adolescents.