Effects of Once-Weekly Sustained-Release Growth Hormone: A Double-Blind, Placebo-Controlled Study in Adult Growth Hormone Deficiency
Effects of Once-Weekly Sustained-Release Growth Hormone: A Double-Blind, Placebo-Controlled Study in Adult Growth Hormone Deficiency
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DOI：
10.1210/jc.2010-2819
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发表时间：
2011-06-01
影响因子：
5.8
通讯作者：
Strasburger, Christian J.
中科院分区：
文献类型：
--
作者：
Biller, Beverly M. K.;Ji, Hyi-Jeong;Strasburger, Christian J.
背景：最近开发了一种缓释重组人 GH 制剂 LB03002，其药代动力学和药效活性适合每周一次给药。 LB03002 是一种长效 GH，每周皮下注射一次。 目的：本研究评估 LB03002 在 GH 缺乏的成年患者中的疗效和安全性。 患者和方法：总共 152 名患者被随机分配接受每周一次的 LB03002 或安慰剂，持续 26 周。通过 DXA（双能 X 射线吸收测定法）评估身体成分的变化。每次研究访问时都会评估 IGF-I。从不良事件、葡萄糖稳态和抗体产生等方面评估安全性。结果：LB03002 组 IGF-I 显着增加（P < 0.001），安慰剂组保持不变。 LB03002 组的平均脂肪量 (FM) 减少了 1.052 kg [95% 置信区间 (CI) = -1.614 至 -0.491]，而安慰剂组则增加了 0.570 kg (95% CI = -0.205-1.345)；治疗差异为 1.622 kg（95% CI = -2.527 至 -0.717；P < 0.001）。 FM 变化主要是由于躯干脂肪减少。最小二乘平均治疗差异为 1.032 kg（95% CI = -1.560 至 -0.515；P < 0.001）。与安慰剂相比，LB03002 组的 LBM（去脂体重）显着增加（最小二乘平均差为 1.393 kg；95% CI = 0.614-2.171；P < 0.001）。研究期间没有出现安全问题。结论：成人每周用缓释制剂 LB03002 替代 GH，6 个月内可显着减少 FM，且耐受性良好。 （临床内分泌代谢杂志 96：1718-1726，2011）
Background: A sustained-release recombinant human GH formulation, LB03002, has been recently developed, with pharmacokinetics and pharmacodynamic activity appropriate for once-weekly administration. LB03002 is a long-acting GH that is administered once a week by sc injection.Objective: This study evaluated efficacy and safety of LB03002 in adult patients with GH deficiency.Patients and Methods: A total of 152 patients were randomized to receive LB03002 or placebo once weekly for 26 wk. Changes in body composition were evaluated from DXA (dual-energy x-ray absorptiometry). IGF-I was assessed at each study visit. Safety was assessed from adverse events, glucose homeostasis, and antibody development.Results: IGF-I increased significantly (P < 0.001) with LB03002 and remained unchanged with placebo. Mean fat mass (FM) decreased by 1.052 kg [95% confidence interval (CI) = -1.614 to -0.491] in the LB03002 group vs. an increase of 0.570 kg (95% CI = -0.205-1.345) in the placebo group; treatment difference was 1.622 kg (95% CI = -2.527 to -0.717; P < 0.001). FM change was mainly due to decreased trunk fat. Least square mean treatment difference was 1.032 kg (95% CI = -1.560 to -0.515; P < 0.001). LBM (lean body mass) was significantly increased with LB03002 vs. placebo (least square mean difference was 1.393 kg; 95% CI = 0.614-2.171; P < 0.001). No concerning safety issues arose during the study.Conclusions: Weekly GH replacement with the sustained-release preparation LB03002 in adults significantly reduced FM over 6 months and was well tolerated. (J Clin Endocrinol Metab 96: 1718-1726, 2011)