Reproductive endocrinology. First human exposure to FSH-CTP in hypogonadotrophic hypogonadal males

• Published in: Human reproduction (Oxford) 2001-08, Vol.16 (8), p.1592
• Main Authors: P.M.G. Bouloux, Handelsman, D J, Jockenhovel, F, Nieschlag, E, Rabinovici, J, W.L.H. Frasa, J.J. de Bie, Voortman, G, Itskovitz-Eldor, J
• Format: Article
• Language: English
• ISSN: 0268-1161; 1460-2350

BACKGROUND: This is the first report of human exposure to the novel compound follicle stimulating hormone (FSH)-C-terminal peptide (CTP) `FSH-CTP' (Org 36286), a long-acting recombinant FSH like substance, consisting of the [alpha]-subunit of human FSH and a hybrid [beta]-subunit. The latter is composed of the [beta]-subunit of human FSH and the C-terminus part (CTP) of the [beta]-subunit of human chorionic gonadotrophin (HCG). METHODS: In this phase I, non-blind, multi-centre study, 13 hypogonadotrophic hypogonadal male subjects were enrolled to test the safety of FSH-CTP in terms of antibody formation in humans. Furthermore, the pharmacokinetic profile of this new compound was determined. Subjects were injected four times with 15 [mu]g FSH-CTP with an interval of ~4 weeks between each injection. RESULTS: No drug related (serious) adverse events occurred. No antibodies against FSH-CTP or chinese hamster ovary (CHO)-cell derived proteins were detected and measurement of local tolerance demonstrated that s.c. administration of FSH-CTP is well tolerated and no increase in intensity of injection-site responses was observed after repeated exposure to FSH-CTP. After the first and third injection, FSH-CTP serum concentrations were determined. Overall mean (+ or - SD) Cmax was 0.426 (+ or - 0.116) ng/ml, mean t 1/2 and AUC0-[infinity] were 94.7 (+ or - 26.2) h and 81.5 (+ or - 18.8) ng.h/ml respectively. Compared with recFSH (Puregon(R)), the half life of FSH-CTP was increased 2-3 times. Following the first and third injection a clear rise in serum inhibin-B concentrations were observed. CONCLUSIONS: The use of FSH-CTP is safe and does not lead to detectable formation of antibodies. Furthermore, the pharmacokinetic and dynamic profile of FSH-CTP may lead to the development of new, more convenient regimens for the treatment of male and female infertility.