Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults.
BACKGROUND
Therapeutic use of GHRH to enhance GH secretion is limited by its short duration of action.


OBJECTIVE
The objective of this study was to examine the pharmacokinetic profile, pharmacodynamic effects, and safety of CJC-1295, a long-acting GHRH analog.


METHODS
The study design was two randomized, placebo-controlled, double-blind, ascending dose trials with durations of 28 and 49 d.


METHODS
The study was performed at two investigational sites.


METHODS
Healthy subjects, ages 21-61 yr, were studied.


METHODS
CJC-1295 or placebo was administered sc in one of four ascending single doses in the first study and in two or three weekly or biweekly doses in the second study.


METHODS
The main outcome measures were peak concentrations and area under the curve of GH and IGF-I; standard pharmacokinetic parameters were used for CJC-1295.


RESULTS
After a single injection of CJC-1295, there were dose-dependent increases in mean plasma GH concentrations by 2- to 10-fold for 6 d or more and in mean plasma IGF-I concentrations by 1.5- to 3-fold for 9-11 d. The estimated half-life of CJC-1295 was 5.8-8.1 d. After multiple CJC-1295 doses, mean IGF-I levels remained above baseline for up to 28 d. No serious adverse reactions were reported.


CONCLUSIONS
Subcutaneous administration of CJC-1295 resulted in sustained, dose-dependent increases in GH and IGF-I levels in healthy adults and was safe and relatively well tolerated, particularly at doses of 30 or 60 microg/kg. There was evidence of a cumulative effect after multiple doses. These data support the potential utility of CJC-1295 as a therapeutic agent.
Teichman
Sam L
SL
WinPharm Associates, Alamo, CA 94507, USA.
Neale
Ann
A
Lawrence
Betty
B
Gagnon
Catherine
C
Castaigne
Jean-Paul
JP
Frohman
Lawrence A
LA
D000328:Adult; D004311:Double-Blind Method; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010919:Placebos; D012016:Reference Values
C502076:CJC 1295; D010446:Peptide Fragments; D010919:Placebos; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone