First human exposure to FSH-CTP in hypogonadotrophic hypogonadal males

BACKGROUND: This is the first report of human exposure to the novel compoun d follicle stimulating hormone (FSH)-C-terminal peptide (CTP) 'FSH-CTP' (Or g 36286), a long-acting recombinant FSH like substance, consisting of the a lpha -subunit of human FSH and a hybrid beta -subunit. The latter is compos ed of the beta -subunit of human FSH and the C-terminus part (CTP) of the b eta -subunit of human chorionic gonadotrophin (HCG). METHODS: In this phase I, non-blind, multi-centre study, 13 hypogonadotrophic hypogonadal male su bjects were enrolled to test the safety of FSH-CTP in terms of antibody for mation in humans. Furthermore, the pharmacokinetic profile of this new comp ound was determined. Subjects were injected four times with 15 mug FSH-CTP with an interval of similar to4 weeks between each injection. RESULTS: No d rug related (serious) adverse events occurred. No antibodies against FSH-CT P or chinese hamster ovary (CHO)-cell derived proteins were detected and me asurement of local tolerance demonstrated that s.c. administration of FSH-C TP is well tolerated and no increase in intensity of injection-site respons es was observed after repeated exposure to FSH-CTP. After the first and thi rd 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-infinity) wer e 94.7 (+/- 26.2) h and 81.5 (+/- 18.8) ng.h/ml respectively. Compared with recFSH (Puregon (R)), the half life of FSH-CTP was increased 2-3 times. Fo llowing the first and third injection a clear rise in serum inhibin-B conce ntrations were observed. CONCLUSIONS: The use of FSH-CTP is safe and does n ot lead to detectable formation of antibodies. Furthermore, the pharmacokin etic and dynamic profile of FSH-CTP may lead to the development of new, mor e convenient regimens for the treatment of male and female infertility.