Pharmacokinetics and Safety of Follitropin Delta in Gonadotropin Down-Regulated Healthy Chinese Women.

Abstract

Follitropin delta, a novel recombinant follicle-stimulating hormone (rFSH) preparation derived from a human cell line, has different pharmacokinetic and pharmacodynamic properties compared with existing rFSH preparations expressed by Chinese hamster ovary cells (CHO). The objective of this study was to assess the pharmacokinetic characteristics, dose proportionality, and safety of follitropin delta in healthy Chinese women. This was a phase I, randomized, open-label study. Twenty-four healthy Chinese women were randomized (1:1:1) to receive a single subcutaneous administration of follitropin delta 12, 18, or 24μg. The pharmacokinetic parameters (maximum observed serum concentration [Cmax], time to reach Cmax [tmax], area under the serum concentration-time curve from dosing to infinity [AUC∞], and elimination phase half-life [t½]) of follitropin delta were derived using noncompartmental analysis. Following a single subcutaneous administration of follitropin delta 12, 18, or 24μg, mean Cmax (0.388, 0.677, and 0.825ng/mL, respectively) and AUC∞ (41.3, 62.9, and 83.1h·ng/mL, respectively) increased in a dose-proportional manner. The median tmax was 24 h, and the mean t½ was in the range of 50.5-60.9 h. All treatment-related adverse events were categorized as mild, except for one case of urticaria from the follitropin delta 18-μg dose group which was considered moderate. Only one woman presented with elevation of alanine transaminase and aspartate aminotransferase at the follow-up visit, which was reported as a treatment-emergent adverse event. There were no injection-site reactions and none of the participants showed any confirmed presence of treatment-induced anti-FSH antibodies. The administration of single doses of follitropin delta to healthy Chinese women demonstrated dose-proportional pharmacokinetics over the dose range of 12-24μg, and these doses were well tolerated. Clinicaltrials.gov registration no. NCT04150861.