薬理と治療

Abstract

Objectives　This study aimed to demonstrate the equivalence in pharmacokinetic（PK）and pharmacodynamic（PD）profiles between MD–110 and reference pegfilgrastim（G–LASTA®） in healthy male volunteers, as well as to assess safety and immunogenicity. Methods　The study was a phase Ⅰ, randomized, double–blind, two–period, two–sequence crossover study. Healthy Japanese male volunteers aged 20–40 were randomized to receive either MD–110 followed by reference pegfilgrastim or reference pegfilgrastim followed by MD–110. Each participant received a single 3.6 mg injection of MD–110 or reference pegfilgrastim on Day 1 of each period. The co–primary endpoints for PK were the maximum serum concentration（Cmax）and area under the serum concentration–time curve（AUCt）. The co–primary endpoints for PD were absolute neutrophil count（ANC）maximum observed effect （Emax）, and ANC area under the effect curve（AUEC）. PK equivalence was claimed if the two–sided 90％ confidence intervals（CI）for the mean difference between treatments of the log–transformed PK co–primary endpoints were within the pre–defined equivalence range（log 0.8 to log 1.25）. A two–sided 95％ CI within the same equivalence range was used for PD equivalence. Results　Eighty participants in Japan were randomized to treatment, and 74 participants received both study treatments. PK/PD equivalence was demonstrated. The CIs of the PK primary endpoint, and the PD primary endpoint, were all within the pre–defined equivalence range. No clinically meaningful differences in safety, including immunogenicity, were observed between MD–110 and reference pegfilgrastim. Conclusions　The study confirms the PK/PD equivalence of MD–110 and reference pegfilgrastim, with no clinically meaningful differences in safety, including immunogenicity.（Jpn Pharmacol Ther 2023；51：1277‒87）