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 plasmaIGF-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.
RCT Entities:
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 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.
Authors: Dinesh Gautam; Jongrye Jeon; Matthew F Starost; Sung-Jun Han; Fadi F Hamdan; Yinghong Cui; Albert F Parlow; Oksana Gavrilova; Ildiko Szalayova; Eva Mezey; Jürgen Wess Journal: Proc Natl Acad Sci U S A Date: 2009-03-30 Impact factor: 11.205
Authors: Andre Knoop; Andreas Thomas; Eric Fichant; Philippe Delahaut; Wilhelm Schänzer; Mario Thevis Journal: Anal Bioanal Chem Date: 2016-02-15 Impact factor: 4.142