Human Reproduction, Vol. 16, No. 8, 1592-1597,
August 2001
© 2001 European Society of Human Reproduction and Embryology
First human exposure to FSH-CTP in hypogonadotrophic hypogonadal males
1 Centre for Neuroendocrinology, University College London, London, UK, 2 ANZAC Research Institute, University of Sydney, Sydney, Australia, 3 Universität zu Köln, Köln, Germany, 4 Westfälische Wilhelms-Universität, Münster, Germany, 5 Sheba Medical Center, Tel Hashomer, Israel, 6 NV Organon, Oss, The Netherlands and 7 Rambam Medical Center, Haifa, Israel
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 
-subunit of human FSH and a hybrid ß-subunit. The latter is composed of the ß-subunit of human FSH and the C-terminus part (CTP) of the ß-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 µg 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 (± SD) Cmax
was 0.426 (± 0.116) ng/ml, mean t
and AUC0-
were 94.7 (± 26.2) h and 81.5 (± 18.8) ng.h/ml respectively. Compared with recFSH (Puregon®), 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.
8 Correspondence should be addressed to: NV Organon, Molenweg 10, PO Box 20, 5340 BH Oss, The Netherlands.E-mail: G.Voortman{at}organon.oss.akzonobel.nl
*For participant details see Acknowledgements section
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