Single dose pharmacokinetics and effects on follicular growth and serum hormones of a long-acting recombinant FSH preparation (FSH-CTP) in healthy pituitary-suppressed females

BACKGROUND: A long-acting FSH preparation has been developed by site-directed mutagenesis and gene transfer techniques. METHODS: In this open-label trial, we investigated the pharmacokinetic and pharmacodynamic properties of FSH-CTP (corifollitropin alpha, Org 36286) in healthy female volunteers. Twenty-four subjects were treated with a high-dose oral contraceptive (OC) to suppress pituitary function. A single dose of 15, 30 or 60 mug FSH-CTP was injected (s.c., eight subjects per dose group) and seven of these 24 subjects were subsequently treated with a single dose of 120 mug. RESULTS: Maximum serum FSH-CTP concentrations (0.42, 0.66, 1.49 and 3.27 ng/ml after administration of 15, 30, 60 and 120 mug Org 36286 respectively) were reached between 36 and 48 h after injection and t(1/2) varied between 60 and 75 h. Dose proportionality was shown across the studied dose range, whereas t(max) and t(1/2) were dose independent. In most subjects follicular growth was observed; the number and maximum diameter of the follicles increased with the dose. Follicles with a diameter greater than or equal to8.0 mm were observed only in the 60 and 120 mug dose groups, diameters between 12.0 and 15.9 mm occurred only in the 120 mug group. Serum LH and 17beta-oestradiol levels remained low due to profound pituitary suppression whereas inhibin-B levels increased with dose. Maximum mean inhibin-B levels were 30.4, 322.7 and 1059.3 pg/ml in the 30, 60 and 120 mug dose group respectively. The preparation was safe and well tolerated, and no FSH-CTP antibody formation was observed. CONCLUSIONS: The pharmacokinetics of FSH-CTP were shown to be proportional with the dose. The elimination half-life was approximately two times longer than that of rFSH. A single dose of FSH-CTP was shown to be safe and able to induce multiple follicular growth accompanied by a dose-dependent rise in serum inhibin-B concentrations.