TV-1106 is a human serum albumin genetically fused to recombinant human growth hormone, designed to provide a long-acting alternative to daily growth hormone (GH) injections in patients with GH deficiency. This study investigated the pharmacokinetics, pharmacodynamics, and safety of single subcutaneous doses of TV-1106 (7.5, 15, 50, and 100 mg) in Japanese (n = 44) and caucasian (n = 44) healthy subjects. TV-1106 pharmacokinetics and pharmacodynamics were comparable in Japanese and caucasian populations. TV-1106 demonstrated relatively slow absorption (median tmax , 10-30 hours) and a mean elimination half-life of 26-36 hours. Apparent clearance and volume of distribution decreased with increasing TV-1106 doses in both populations and appeared to increase more than dose proportionality across the tested doses. Insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) increased in a dose-related manner, with maximum responses observed at 33-96 and 42-109 hours, respectively. IGF-1 and IGFBP-3 returned to baseline values at 168 hours following 7.5 and 15 mg of TV-1106, and 336 hours following 50 and 100 mg of TV-1106. TV-1106 appeared safe in both populations. There was no evidence of differences in pharmacokinetics, pharmacodynamics, or safety of TV-1106 between Japanese and caucasian populations. The data also demonstrate long-acting growth hormone properties of TV-1106 and support its potential for once-weekly dosing.

译文

:TV-1106是人血清白蛋白,与重组人生长激素基因融合,旨在为GH缺乏症患者的日常生长激素(GH)注射提供长效替代品。这项研究调查了日本(n = 44)和高加索人(n = 44)健康受试者单次皮下注射TV-1106(7.5、15、50和100 mg)的药代动力学,药效学和安全性。在日本和白种人中,TV-1106的药代动力学和药效学相当。 TV-1106表现出相对较慢的吸收(tmax中位数为10-30小时),平均消除半衰期为26-36小时。在两个人群中,表观清除率和分布体积均随着TV-1106剂量的增加而降低,并且似乎在整个测试剂量中的增加均大于剂量比例。胰岛素样生长因子-1(IGF-1)和IGF结合蛋白-3(IGFBP-3)以剂量相关的方式增加,分别在33-96和42-109小时观察到最大反应。 IGF-1和IGFBP-3在7.5和15 mg TV-1106服用后168小时以及在50和100 mg TV-1106服用后336小时回到基线值。 TV-1106在两种人群中均显示安全。没有证据表明日本人和白种人之间的药代动力学,药效学或TV-1106的安全性存在差异。数据还证明了TV-1106的长效生长激素特性,并支持其每周一次给药的潜力。

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