Phase 3 trial of a small-volume subcutaneous 6-month duration leuprolide acetate treatment for central precocious puberty

2021 ◽  
Author(s):  
Klein KO ◽  
Freire A ◽  
Gryngarten MG ◽  
Kletter GB ◽  
Benson M ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Small Volume ◽  
Central Precocious Puberty ◽  
Leuprolide Acetate ◽  
Phase 3

scholarly journals Phase 3 Trial of a Small-volume Subcutaneous 6-Month Duration Leuprolide Acetate Treatment for Central Precocious Puberty

2020 ◽  
Vol 105 (10) ◽  
pp. e3660-e3671
Author(s):  
Karen O Klein ◽  
Analía Freire ◽  
Mirta Graciela Gryngarten ◽  
Gad B Kletter ◽  
Matthew Benson ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Small Volume ◽  
Study Drug ◽  
External Genitalia ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Leuprolide Acetate ◽  
Open Label ◽  
Phase 3 ◽  
Pubertal Stage

Abstract Context Gonadotropin-releasing hormone agonists (GnRHas) are standard of care for central precocious puberty (CPP). A 6-month subcutaneous injection has recently been approved by the Food and Drug Administration. Objective Determine efficacy, pharmacokinetics, and safety of 6-month 45-mg subcutaneous leuprolide acetate for CPP. Design Phase 3 multicenter, open-label, single-arm study. Setting 25 sites in 6 countries. Subjects 64 GnRHa-naïve children with CPP (age: 7.5 ± 0.1 years) received study drug: 59 completed the study. Intervention(s) 2 doses of 45-mg subcutaneous leuprolide acetate (0.375 mL) at 0 and 24 weeks; children were followed for 48 weeks. Main Outcome Measure(s) Percentage of children with serum luteinizing hormone (LH) <4 IU/L 30 minutes following GnRHa stimulation at week 24. Results 54/62 (87%) children achieved poststimulation LH <4 IU/L at week 24; 49/56 (88%) girls and 1/2 boys maintained peak LH <4 IU/L at week 48. Mean growth velocity decreased from 8.9 cm/year at week 4 to 6.0 cm/year at week 48. Mean bone age was advanced 3.0 years beyond chronological age at screening and 2.7 years at week 48. Breast pubertal stage regressed or was stable in 97% of girls and external genitalia development regressed in both boys. Adverse events were mild and did not cause treatment discontinuation. Conclusions A small volume of 45-mg subcutaneous leuprolide acetate administered at a 6-month interval effectively suppressed pubertal hormones and stopped or caused regression of pubertal progression. This long-acting GnRHa preparation of leuprolide acetate is a new, effective, and well-tolerated therapy for children with CPP.

Comparison of three doses of leuprolide acetate in the treatment of central precocious puberty: preliminary results

2009 ◽  
Vol 71 (5) ◽  
pp. 686-690 ◽  
Author(s):  
Verónica Mericq ◽  
Juan Javier Lammoglia ◽  
Nancy Unanue ◽  
Claudio Villaroel ◽  
María Isabel Hernández ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
Leuprolide Acetate ◽  
Preliminary Results

scholarly journals Leuprolide Acetate 1-Month Depot for Central Precocious Puberty: Hormonal Suppression and Recovery

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
E. Kirk Neely ◽  
Peter A. Lee ◽  
Clifford A. Bloch ◽  
Lois Larsen ◽  
Di Yang ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
Leuprolide Acetate

Monitoring treatment of central precocious puberty using basal luteinizing hormone levels and practical considerations for dosing with a 3-month leuprolide acetate formulation

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Peter A. Lee ◽  
Margaret Luce ◽  
Peter Bacher
Keyword(s):  
Luteinizing Hormone ◽  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
Gonadotropin Releasing Hormone ◽  
Leuprolide Acetate ◽  
Open Label ◽  
Predictive Values ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
Monitoring Treatment

AbstractBackground:Peak gonadotropin-releasing hormone or agonist (GnRHa) stimulated luteinizing hormone (LH) testing with leuprolide acetate (LA) is commonly used to document suppression during therapy for central precocious puberty (CPP). The objective of the study was to investigate suitability of using basal LH levels to monitor GnRHa treatment and to determine optimal transition from 1-month to 3-month LA formulations via a post hoc analysis of a randomized, open-label, 6-month study.Methods:A total of 42 children with CPP, pretreated with 7.5-, 11.25-, or 15-mg 1-month LA formulations were randomized to 11.25- or 30-mg 3-month LA. Basal LH/peak-stimulated LH levels were measured at weeks 0, 4, 8 and 12. Positive/negative predictive values and sensitivities/specificities were determined for basal LH vs. LH-stimulation results.Results:Pretreatment with any 1-month formulation for the most part did not affect continuation of suppression after transitioning to 3-month formulation (mean peak-stimulated LH levels remained < 4 IU/L). Basal LH predicted suppression escape (basal LH-level cutoff ≥ 0.6 IU/L predicted 70% of those failing suppression). Tolerability was similar, regardless of dose.Conclusions:Our data indicate that a basal level of <0.60 IU/L is adequate for monitoring suppression approximately two-thirds of the time. Furthermore, the effectiveness and safety of 3-month LA treatments are not influenced by previous CPP therapies.

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