Abstract | 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 microg FSH-CTP with an interval of approximately 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 t(1/2) and AUC(0-infinity) 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.
|
Authors | P M Bouloux, D J Handelsman, F Jockenhövel, E Nieschlag, J Rabinovici, W L Frasa, J J de Bie, G Voortman, J Itskovitz-Eldor, FSH-CTP study group |
Journal | Human reproduction (Oxford, England)
(Hum Reprod)
Vol. 16
Issue 8
Pg. 1592-7
(Aug 2001)
ISSN: 0268-1161 [Print] England |
PMID | 11473948
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Multicenter Study)
|
Chemical References |
- Antibodies
- Antigens
- Chorionic Gonadotropin, beta Subunit, Human
- Follicle Stimulating Hormone, Human
- Follicle Stimulating Hormone, beta Subunit
- Glycoprotein Hormones, alpha Subunit
- Recombinant Fusion Proteins
- follicle stimulating hormone, human, with HCG C-terminal peptide
- Testosterone
- Estradiol
- Inhibins
- Follicle Stimulating Hormone
|
Topics |
- Adult
- Animals
- Antibodies
(blood)
- Antigens
(immunology)
- CHO Cells
(immunology)
- Chorionic Gonadotropin, beta Subunit, Human
- Cricetinae
- Estradiol
(blood)
- Follicle Stimulating Hormone
(adverse effects, pharmacokinetics, therapeutic use)
- Follicle Stimulating Hormone, Human
- Follicle Stimulating Hormone, beta Subunit
- Glycoprotein Hormones, alpha Subunit
- Half-Life
- Humans
- Hypogonadism
(drug therapy)
- Inhibins
(blood)
- Kinetics
- Male
- Middle Aged
- Recombinant Fusion Proteins
(immunology, therapeutic use)
- Testosterone
(blood)
|