Accord Healthcare, Sage House, 319 Pinner Road, North Harrow, Middlesex, HA1 4HF, UK.
Intas Pharmaceuticals Limited, Corporate House, Near Sola Bridge, S.G. Highway, Thaltej, Ahmedabad, 380054, Gujarat, India.
Osteoporos Int. 2023 Jan;34(1):179-188. doi: 10.1007/s00198-022-06573-x. Epub 2022 Oct 26.
Biosimilar teriparatide (INTG-8) was tested in a healthy population of males and postmenopausal females to assess pharmacokinetic bioequivalence to originator teriparatide comparator products. Primary pharmacokinetic comparison confirmed bioequivalence. Pharmacodynamics, safety, and tolerability were comparable to the originator products. INTG-8 was therefore confirmed to be biosimilar to originator products.
The purpose of this present study was to demonstrate pharmacokinetic (PK) equivalence of a biosimilar teriparatide (INTG8) to EU- and US-approved teriparatide reference products in healthy men and postmenopausal women. Secondary objectives included comparison of the pharmacodynamics (PD), safety, and tolerability.
One hundred and five subjects randomly (1:1:1) received single subcutaneous 20 μg injection of teriparatide biosimilar, EU- and US-teriparatide on 3 consecutive days in this assessor-blind, three-period, single-dose, crossover study. Maximum serum concentration (C), area under the curve (AUC) from time zero to t (AUC), and AUC from time zero extrapolated to infinity (AUC) were primary PK parameters, analyzed by non-compartmental methods. The secondary PD endpoints were maximum observed effect (E), area under the effect curve (AUE) from time zero to the last measurable concentration (AUE), and time to maximum observed effect (Tmax) for total serum calcium levels. Safety, tolerability, and immunogenicity were also evaluated. This study was registered with ctri.nic.in/ (CTRI/2020/10/028627) on 26 October 2020.
Baseline demographics were similar across the three-treatment sequence groups. The 90% confidence intervals (CI) for the geometric mean ratios (test:reference) of Cmax, AUC, and AUC were within the predefined bioequivalence criterion of 80.00% to 125.00%, which demonstrated PK equivalence of teriparatide biosimilar to EU- and US-teriparatide for all primary endpoints. The PD comparability was demonstrated by similar serum calcium levels. Study treatments were generally well tolerated and showed no meaningful differences in safety or immunogenicity profiles. There were no deaths, or serious AEs were reported during this study.
The study demonstrated PK bioequivalence of teriparatide biosimilar to the EU- and US-teriparatide reference products with comparable PD, safety, and immunogenicity profiles.
本研究旨在证明一种生物类似物特立帕肽（INTG8）在健康男性和绝经后女性中的药代动力学（PK）等效性与欧盟和美国批准的特立帕肽参比产品相当。次要目标包括比较药效学（PD）、安全性和耐受性。
在这项评估者盲、三周期、单剂量、交叉研究中，105 名受试者随机（1:1:1）在 3 天内分别接受单次皮下 20μg 注射的特立帕肽生物类似物、欧盟和美国特立帕肽。主要 PK 参数包括最大血清浓度（C）、从零时到 t 的曲线下面积（AUC）和从零时外推到无穷大的 AUC（AUC），采用非房室分析方法进行分析。次要 PD 终点为总血清钙水平的最大观察效应（E）、从零时到最后可测量浓度的效应下面积（AUE）和最大观察效应时间（Tmax）。还评估了安全性、耐受性和免疫原性。该研究于 2020 年 10 月 26 日在 ctri.nic.in/（CTRI/2020/10/028627）上注册。
三组治疗序列的基线人口统计学特征相似。Cmax、AUC 和 AUC 的几何均数比值（试验：参考）的 90%置信区间（CI）在 80.00%至 125.00%的预设生物等效性标准范围内，表明特立帕肽生物类似物与欧盟和美国特立帕肽参比产品在所有主要终点均具有 PK 等效性。PD 可比性通过相似的血清钙水平得到证明。研究治疗通常具有良好的耐受性，在安全性或免疫原性特征方面没有明显差异。在这项研究中没有死亡或严重的 AE 报告。
该研究表明，特立帕肽生物类似物与欧盟和美国特立帕肽参比产品具有 PK 生物等效性，具有相当的 PD、安全性和免疫原性特征。
