Toffoletto Odaly, Afiune Jorge, Thiemann Josef Ernst, Khandave Suhas S, Patel Swati, Rodrigues Debora G
Cristália Produtos Químicos Farmacêuticos, Ltda Highway Itapira-Lindóia, Km 14 - Ponte Preta, CEP: 13970-970 Itapira, SP, Brazil.
Accutest Research Laboratories (I), Pvt. Ltd., A-31, M.I.D.C, T.T.C Industrial Area, Khairane, Navi Mumbai 400709, Maharashtra, India.
Growth Horm IGF Res. 2016 Oct-Dec;30-31:31-36. doi: 10.1016/j.ghir.2016.09.003. Epub 2016 Sep 16.
To extend available dosing options in the treatment of growth hormone deficiency, a comparative pharmacokinetic and pharmacodynamic phase-1 clinical study involving subcutaneous administration of growth hormone was conducted.
The test formulation (biosimilar recombinant human growth hormone; r-hGH; Somatotropin) and reference formulation (Genotropin®) were tested in 38 adult healthy subjects after their subcutaneous administration of 12.8IU in an open label, single dose, randomized, two period cross over study separated with a washout period of 11days. Endogenous growth hormone release was suppressed by a continuous Octreotide infusion up to 24h after r-hGH administration. All the subjects were evaluated for local tolerance using Wong-Baker Faces pain rating scale and an injection site reaction (ISR) score. Detection of serum levels of r-hGH, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) was done by suitable validated bio-analytical methods. Assessment of bioequivalence for pharmacokinetic parameters was done using log-transformed area under the curve (AUC) and maximum concentration (C) for r-hGH. The pharmacodynamic assessment was done by comparing the area under the effect-time curve (AUEClast) and maximum measured effect concentration (E) of IGF-1 and IGFBP-3.
The biosimilar formulation of recombinant human growth hormone fulfilled the predefined bioequivalence criteria for pharmacokinetic and pharmacodynamic parameters.
The new biosimilar recombinant human growth hormone bears the potential to become an alternative option for the treatment of growth hormone deficiency.
为了扩展生长激素缺乏症治疗中的可用给药方案，开展了一项涉及皮下注射生长激素的比较药代动力学和药效学1期临床研究。
在一项开放标签、单剂量、随机、两阶段交叉研究中，对38名成年健康受试者皮下注射12.8IU的试验制剂（生物类似物重组人生长激素；r-hGH；生长激素）和参比制剂（健高素®），两阶段之间有11天的洗脱期。在注射r-hGH后长达24小时内，通过持续输注奥曲肽抑制内源性生长激素释放。使用面部表情疼痛评分量表和注射部位反应（ISR）评分对所有受试者进行局部耐受性评估。通过适当的经过验证的生物分析方法检测血清中r-hGH、胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）的水平。使用r-hGH的对数转换曲线下面积（AUC）和最大浓度（C）评估药代动力学参数的生物等效性。通过比较IGF-1和IGFBP-3的效应-时间曲线下面积（AUEClast）和最大测量效应浓度（E）进行药效学评估。
重组人生长激素的生物类似物制剂符合药代动力学和药效学参数的预定义生物等效标准。
新型生物类似物重组人生长激素有潜力成为治疗生长激素缺乏症的替代选择。
