Dose-Exposure Proportionality of a Novel Recombinant Follicle-Stimulating Hormone (rFSH), FE 999049, Derived from a Human Cell Line, with Comparison Between Caucasian and Japanese Women After Subcutaneous Administration

Abstract

Background and Objectives: FE 999049 is a novel recombinant follicle-stimulating hormone (rFSH) preparation expressed by a human cell line (PER.C6®), in contrast to existing rFSH preparations expressed by Chinese hamster ovary (CHO) cell lines. Since the individual dose of rFSH may be altered depending on the response in women undergoing assisted reproductive technologies, knowledge on the dose-exposure linearity and proportionality is important. The purpose of these studies was to investigate the dose-exposure linearity and proportionality properties of FE 999049 with a comparison between Caucasian and Japanese women. This is the first study in Japanese women regarding pharmacokinetics of rFSH. Methods: Forty-eight Caucasian and 31 Japanese healthy women of reproductive age were pituitary down-regulated to suppress endogenous FSH. Following single subcutaneous administration of 37.5, 75, 150, 225, or 450 IU (Steelman–Pohley assay), the serum FSH concentration was followed over 10 days. Results: The dose-dependent pharmacokinetic parameters of FE 999049, area under the serum concentration-time curve (AUC) and maximum serum concentration (Cmax), showed dose-exposure linearity and proportionality over 150–450 IU in Caucasian women, the dose interval available for analysis, and 75–450 IU in Japanese women, which was the dose interval investigated. Comparison between Caucasian and Japanese women showed no differences between the populations. The dose-independent parameters were similar over all doses in both populations. FE 999049 was safe and well tolerated at all doses in both populations with few, mostly mild, adverse events. Conclusion: The results demonstrate dose-exposure proportionality and a predictable dose-dependent exposure of FE 999049, with no differences in Caucasian and Japanese women of reproductive age.