CONTEXT: GnRH agonist (GnRHa) monthly injections are frequently used in the treatment of central precocious puberty (CPP). The 3-month leuprolide depot 11.25- and 30-mg formulations are newly approved treatment options. OBJECTIVE: The aim of the study was to investigate the safety and efficacy of leuprolide acetate 3-month depot formulations for the treatment of CPP in children. DESIGN: This was a phase III, randomized, open-label, dose-ranging 6-month study. SETTING:Twenty-two U.S. medical centers (including Puerto Rico) participated. PATIENTS: Children diagnosed with CPP (n = 84), who were either treatment naive or previously treated with GnRHa, were recruited. Chronological age at onset of pubertal signs was less than 8 yr in girls and less than 9 yr in boys, and bone age was advanced over chronological age at least 1 yr. INTERVENTION: Leuprolide acetate depot (11.25 or 30 mg) was administered im every 3 months. MAIN OUTCOME MEASURES: Biochemical [peak-stimulated LH, estradiol (girls), and testosterone (boys)] and anthropometric (growth rate, bone age acceleration, pubertal progression) parameters and safety were assessed. RESULTS:Peak-stimulated LH was suppressed in the 11.25- and 30-mg dose groups in 78.4 and 95.2%, respectively, of children from months 2 through 6. There were nine treatment failures (peak-stimulated LH >4 IU/liter) in the 11.25-mg group and two in the 30-mg group. Basal sex steroid suppression, growth rates, pubertal progression, bone age advancement, and adverse events were similar with either dose. CONCLUSIONS: Treatment with leuprolide acetate 3-month depot formulations (11.25 and 30 mg) effectively suppressed the GnRH axis, was well tolerated, and may positively impact patient convenience and compliance.
RCT Entities:
CONTEXT: GnRH agonist (GnRHa) monthly injections are frequently used in the treatment of central precocious puberty (CPP). The 3-month leuprolide depot 11.25- and 30-mg formulations are newly approved treatment options. OBJECTIVE: The aim of the study was to investigate the safety and efficacy of leuprolide acetate 3-month depot formulations for the treatment of CPP in children. DESIGN: This was a phase III, randomized, open-label, dose-ranging 6-month study. SETTING: Twenty-two U.S. medical centers (including Puerto Rico) participated. PATIENTS: Children diagnosed with CPP (n = 84), who were either treatment naive or previously treated with GnRHa, were recruited. Chronological age at onset of pubertal signs was less than 8 yr in girls and less than 9 yr in boys, and bone age was advanced over chronological age at least 1 yr. INTERVENTION: Leuprolide acetate depot (11.25 or 30 mg) was administered im every 3 months. MAIN OUTCOME MEASURES: Biochemical [peak-stimulated LH, estradiol (girls), and testosterone (boys)] and anthropometric (growth rate, bone age acceleration, pubertal progression) parameters and safety were assessed. RESULTS: Peak-stimulated LH was suppressed in the 11.25- and 30-mg dose groups in 78.4 and 95.2%, respectively, of children from months 2 through 6. There were nine treatment failures (peak-stimulated LH >4 IU/liter) in the 11.25-mg group and two in the 30-mg group. Basal sex steroid suppression, growth rates, pubertal progression, bone age advancement, and adverse events were similar with either dose. CONCLUSIONS: Treatment with leuprolide acetate 3-month depot formulations (11.25 and 30 mg) effectively suppressed the GnRH axis, was well tolerated, and may positively impact patient convenience and compliance.
Authors: Jadranka Popovic; Mitchell E Geffner; Alan D Rogol; Lawrence A Silverman; Paul B Kaplowitz; Nelly Mauras; Philip Zeitler; Erica A Eugster; Karen O Klein Journal: Front Pediatr Date: 2022-10-04 Impact factor: 3.569
Authors: Ruben H Willemsen; Daniela Elleri; Rachel M Williams; Ken K Ong; David B Dunger Journal: Nat Rev Endocrinol Date: 2014-04-08 Impact factor: 43.330
Authors: E Kirk Neely; Lawrence A Silverman; Mitchell E Geffner; Theodore M Danoff; Errol Gould; Paul S Thornton Journal: Int J Pediatr Endocrinol Date: 2013-12-02
Authors: Karen O Klein; Analía Freire; Mirta Graciela Gryngarten; Gad B Kletter; Matthew Benson; Bradley S Miller; Tala S Dajani; Erica A Eugster; Nelly Mauras Journal: J Clin Endocrinol Metab Date: 2020-10-01 Impact factor: 5.958