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

Autor: Shao F; Phase I Clinical Trial Unit, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.; Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China., Jiang Y; Gynecology Department, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China., Ding S; Phase I Clinical Trial Unit, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China., Larsson P; Global Biometrics, Ferring Pharmaceuticals, Amager Strandvej 405, 2770, Kastrup, Denmark., Pinton P; Global Translational and Clinical Research and Development, Ferring Pharmaceuticals, Amager Strandvej 405, 2770, Kastrup, Denmark., Jonker DM; Global Translational and Clinical Research and Development, Ferring Pharmaceuticals, Amager Strandvej 405, 2770, Kastrup, Denmark. daniel.jonker@ferring.com.
Jazyk: angličtina
Zdroj: Clinical drug investigation [Clin Drug Investig] 2023 Jan; Vol. 43 (1), pp. 37-44. Date of Electronic Publication: 2022 Dec 07.
DOI: 10.1007/s40261-022-01232-9
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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