Comparative Pharmacokinetics, Bioequivalence and Safety Study of Two Recombinant Human Chorionic Gonadotropin Injections in Healthy Chinese Subjects

OBJECTIVE: To evaluate the pharmacokinetics (PK), bioequivalence and safety profile of the recombinant human chorionic gonadotropin (r-hCG) injection formulation LZM003 (test drug) comparing with that of Ovidrel(®) (reference drug) in healthy Chinese subjects. METHODS: This is a randomized, single-blind, single-dose, two-arm and two-period crossover Phase I study. Subjects were randomized evenly to a single dose of LZM003 or reference drug injected subcutaneously, with a 10-day or longer between-treatment washout period. PK parameters, anti-drug antibodies (ADAs), and adverse events (AEs) were assessed. The primary PK endpoints were area under the curve (AUC) of the concentration–time curve from zero to last quantifiable concentration (AUC(0-t)), AUC from zero to infinity (AUC(0-∞)), and peak concentration (C(max)). Bioequivalence was determined by assessing whether the 90% confidence intervals (CIs) for the geometric mean ratio (GMR) of LZM003 to reference drug fell within predefined margins of 80% −125%. RESULTS: Forty-eight subjects (24 males and 24 females) were enrolled and one subject withdrew for personal reasons. Mean values of primary PK parameters were similar (p > 0.05) between LZM003 and the reference drug. The 90% CIs for primary PK endpoints’ GMR of LZM003 to reference drug ranged between 0.9144 and 1.1845, which were within bioequivalence margins of 80−125%. Incidence of AEs was similar (p > 0.05) between the two groups. Neither LZM003 nor reference drug produced anti-drug antibody (ADA) in healthy subjects. CONCLUSION: LZM003 and reference drug were bioequivalent. The PK and safety assessments were similar (p > 0.05) between the two formulations in healthy Chinese subjects. TRIAL REGISTRATION NUMBER: ChiCTR-IIR-16010158 (http://www.chictr.org.cn). TRIAL REGISTRATION DATE: December 15, 2016.