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

BACKGROUND: 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). OBJECTIVES: The objective of this study was to assess the pharmacokinetic characteristics, dose proportionality, and safety of follitropin delta in healthy Chinese women. METHODS: 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 24 μg. The pharmacokinetic parameters (maximum observed serum concentration [C(max)], time to reach C(max) [t(max)], area under the serum concentration–time curve from dosing to infinity [AUC(∞)], and elimination phase half-life [t(½)]) of follitropin delta were derived using noncompartmental analysis. RESULTS: Following a single subcutaneous administration of follitropin delta 12, 18, or 24 μg, mean C(max) (0.388, 0.677, and 0.825 ng/mL, respectively) and AUC(∞) (41.3, 62.9, and 83.1 h·ng/mL, respectively) increased in a dose-proportional manner. The median t(max) was 24 h, and the mean t(½) 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. CONCLUSIONS: The administration of single doses of follitropin delta to healthy Chinese women demonstrated dose-proportional pharmacokinetics over the dose range of 12–24 μg, and these doses were well tolerated. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov registration no. NCT04150861.