First human exposure to FSH-CTP in hypogonadotrophic hypogonadal males

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 α-subunit of human FSH and a hybrid β-subunit. The latter is composed of the β-subunit of human FSH and the C-terminus part (CTP) of the β-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) C_max was 0.426 (± 0.116) ng/ml, mean t1/2 and AUC_0-∞ 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.