Journal Article

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

Jonker, Daniël Martijn, Jiang, Yi, Shao, Feng, Ding, Sijia, Pinton, Philippe, Larsson, Per

2023

Overview

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.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Animals / CHO Cells / Cricetinae / Cricetulus / Female / Follicle Stimulating Hormone / Follicle Stimulating Hormone, Human - adverse effects / Follicle Stimulating Hormone, Human - pharmacokinetics / Humans / Internal Medicine / Medicine / Medicine & Public Health / NCT / NCT04150861 / Original / Original Research Article / Ovaries / Pharmacokinetics / Pharmacology/Toxicology / Pharmacotherapy / Quality control / Regulatory approval / Womens health