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

• Published in: The journal of clinical endocrinology and metabolism 2006-03, Vol.91 (3), p.799-805
• Main Authors: Teichman, Sam L., Neale, Ann, Lawrence, Betty, Gagnon, Catherine, Castaigne, Jean-Paul, Frohman, Lawrence A.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Double-Blind Method; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Growth Hormone-Releasing Hormone - administration & dosage; Growth Hormone-Releasing Hormone - analogs & derivatives; Growth Hormone-Releasing Hormone - pharmacokinetics; Growth Hormone-Releasing Hormone - pharmacology; Human Growth Hormone - secretion; Humans; Injections, Subcutaneous; Insulin-Like Growth Factor I - secretion; Medical sciences; Middle Aged; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacokinetics; Peptide Fragments - pharmacology; Placebos; Reference Values; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2005-1536

Context: 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. Design: The study design was two randomized, placebo-controlled, double-blind, ascending dose trials with durations of 28 and 49 d. Setting: The study was performed at two investigational sites. Participants: Healthy subjects, ages 21–61 yr, were studied. Interventions: 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. Main Outcome Measures: 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 μg/kg. There was evidence of a cumulative effect after multiple doses. These data support the potential utility of CJC-1295 as a therapeutic agent.