Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: A multicenter trial

Erica A. Eugster, William Clarke, Gad B. Kletter, Peter A. Lee, E. Kirk Neely, Edward O. Reiter, Paul Saenger, Dorothy Shulman, Lawrence Silverman, Lisa Flood, William Gray, David Tierney

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Context: GnRH analog (GnRHa) therapy for central precocious puberty (CPP) typically involves im injections. The histrelin implant is a new treatment that provides a continuous slow release of the GnRHa histrelin. Objective: The objective of the study was to investigate the safety and efficacy of the subdermal histrelin implant for the treatment of CPP in treatment naive and previously treated children. Design:This was a phase III, open-label, prospective study of 1-yr duration. Setting: The study was conducted at nine U.S. medical centers. Patients: Girls ages 2-8 yr (naive) or 2-10 yr (previously treated) and boys 2-9 yr (naive) or 2-11 yr (previously treated) with clinical evidence of CPP and a pretreatment pubertal response to leuprolide stimulation were eligible. Intervention: A 50-mg histrelin implant was inserted sc in the inner upper arm. Main Outcome Measures: Peak LH after GnRHa stimulation testing and estradiol (girls) and testosterone (boys) were the main outcome measures. Results: Thirty-six subjects (20 naive) were enrolled. By 1 month, peak LH fell from 28.2 ± 19.97 (naive) to 0.8 ± 0.39 mIU/ml (P < 0.0001) and from 2.1 ± 2.15 (previously treated) to 0.5 ± 0.32 mIU/ml (P < 0.0056). Estradiol suppressed from 24.5 ± 22.27 (naive) to 5.9 ± 2.37 pg/ml (P = 0.0016) and remained suppressed in previously treated subjects, as did testosterone. Suppression was maintained throughout the study. No significant adverse events occurred. Conclusions: The subdermal histrelin implant achieves and maintains excellent suppression of peak LH and sex steroid levels for 1 yr in children with CPP. The treatment is well tolerated. Long-term studies are needed to confirm these results.

Original languageEnglish (US)
Pages (from-to)1697-1704
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number5
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Fingerprint

Multicenter Studies
Safety
Gonadotropin-Releasing Hormone
Testosterone
Estradiol
Outcome Assessment (Health Care)
Leuprolide
Therapeutics
Labels
Arm
Steroids
histrelin
Central Precocious Puberty
Prospective Studies
Injections
Testing

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Eugster, Erica A. ; Clarke, William ; Kletter, Gad B. ; Lee, Peter A. ; Neely, E. Kirk ; Reiter, Edward O. ; Saenger, Paul ; Shulman, Dorothy ; Silverman, Lawrence ; Flood, Lisa ; Gray, William ; Tierney, David. / Efficacy and safety of histrelin subdermal implant in children with central precocious puberty : A multicenter trial. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 5. pp. 1697-1704.
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abstract = "Context: GnRH analog (GnRHa) therapy for central precocious puberty (CPP) typically involves im injections. The histrelin implant is a new treatment that provides a continuous slow release of the GnRHa histrelin. Objective: The objective of the study was to investigate the safety and efficacy of the subdermal histrelin implant for the treatment of CPP in treatment naive and previously treated children. Design:This was a phase III, open-label, prospective study of 1-yr duration. Setting: The study was conducted at nine U.S. medical centers. Patients: Girls ages 2-8 yr (naive) or 2-10 yr (previously treated) and boys 2-9 yr (naive) or 2-11 yr (previously treated) with clinical evidence of CPP and a pretreatment pubertal response to leuprolide stimulation were eligible. Intervention: A 50-mg histrelin implant was inserted sc in the inner upper arm. Main Outcome Measures: Peak LH after GnRHa stimulation testing and estradiol (girls) and testosterone (boys) were the main outcome measures. Results: Thirty-six subjects (20 naive) were enrolled. By 1 month, peak LH fell from 28.2 ± 19.97 (naive) to 0.8 ± 0.39 mIU/ml (P < 0.0001) and from 2.1 ± 2.15 (previously treated) to 0.5 ± 0.32 mIU/ml (P < 0.0056). Estradiol suppressed from 24.5 ± 22.27 (naive) to 5.9 ± 2.37 pg/ml (P = 0.0016) and remained suppressed in previously treated subjects, as did testosterone. Suppression was maintained throughout the study. No significant adverse events occurred. Conclusions: The subdermal histrelin implant achieves and maintains excellent suppression of peak LH and sex steroid levels for 1 yr in children with CPP. The treatment is well tolerated. Long-term studies are needed to confirm these results.",
author = "Eugster, {Erica A.} and William Clarke and Kletter, {Gad B.} and Lee, {Peter A.} and Neely, {E. Kirk} and Reiter, {Edward O.} and Paul Saenger and Dorothy Shulman and Lawrence Silverman and Lisa Flood and William Gray and David Tierney",
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Eugster, EA, Clarke, W, Kletter, GB, Lee, PA, Neely, EK, Reiter, EO, Saenger, P, Shulman, D, Silverman, L, Flood, L, Gray, W & Tierney, D 2007, 'Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: A multicenter trial', Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 5, pp. 1697-1704. https://doi.org/10.1210/jc.2006-2479

Efficacy and safety of histrelin subdermal implant in children with central precocious puberty : A multicenter trial. / Eugster, Erica A.; Clarke, William; Kletter, Gad B.; Lee, Peter A.; Neely, E. Kirk; Reiter, Edward O.; Saenger, Paul; Shulman, Dorothy; Silverman, Lawrence; Flood, Lisa; Gray, William; Tierney, David.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 5, 01.01.2007, p. 1697-1704.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy and safety of histrelin subdermal implant in children with central precocious puberty

T2 - A multicenter trial

AU - Eugster, Erica A.

AU - Clarke, William

AU - Kletter, Gad B.

AU - Lee, Peter A.

AU - Neely, E. Kirk

AU - Reiter, Edward O.

AU - Saenger, Paul

AU - Shulman, Dorothy

AU - Silverman, Lawrence

AU - Flood, Lisa

AU - Gray, William

AU - Tierney, David

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Context: GnRH analog (GnRHa) therapy for central precocious puberty (CPP) typically involves im injections. The histrelin implant is a new treatment that provides a continuous slow release of the GnRHa histrelin. Objective: The objective of the study was to investigate the safety and efficacy of the subdermal histrelin implant for the treatment of CPP in treatment naive and previously treated children. Design:This was a phase III, open-label, prospective study of 1-yr duration. Setting: The study was conducted at nine U.S. medical centers. Patients: Girls ages 2-8 yr (naive) or 2-10 yr (previously treated) and boys 2-9 yr (naive) or 2-11 yr (previously treated) with clinical evidence of CPP and a pretreatment pubertal response to leuprolide stimulation were eligible. Intervention: A 50-mg histrelin implant was inserted sc in the inner upper arm. Main Outcome Measures: Peak LH after GnRHa stimulation testing and estradiol (girls) and testosterone (boys) were the main outcome measures. Results: Thirty-six subjects (20 naive) were enrolled. By 1 month, peak LH fell from 28.2 ± 19.97 (naive) to 0.8 ± 0.39 mIU/ml (P < 0.0001) and from 2.1 ± 2.15 (previously treated) to 0.5 ± 0.32 mIU/ml (P < 0.0056). Estradiol suppressed from 24.5 ± 22.27 (naive) to 5.9 ± 2.37 pg/ml (P = 0.0016) and remained suppressed in previously treated subjects, as did testosterone. Suppression was maintained throughout the study. No significant adverse events occurred. Conclusions: The subdermal histrelin implant achieves and maintains excellent suppression of peak LH and sex steroid levels for 1 yr in children with CPP. The treatment is well tolerated. Long-term studies are needed to confirm these results.

AB - Context: GnRH analog (GnRHa) therapy for central precocious puberty (CPP) typically involves im injections. The histrelin implant is a new treatment that provides a continuous slow release of the GnRHa histrelin. Objective: The objective of the study was to investigate the safety and efficacy of the subdermal histrelin implant for the treatment of CPP in treatment naive and previously treated children. Design:This was a phase III, open-label, prospective study of 1-yr duration. Setting: The study was conducted at nine U.S. medical centers. Patients: Girls ages 2-8 yr (naive) or 2-10 yr (previously treated) and boys 2-9 yr (naive) or 2-11 yr (previously treated) with clinical evidence of CPP and a pretreatment pubertal response to leuprolide stimulation were eligible. Intervention: A 50-mg histrelin implant was inserted sc in the inner upper arm. Main Outcome Measures: Peak LH after GnRHa stimulation testing and estradiol (girls) and testosterone (boys) were the main outcome measures. Results: Thirty-six subjects (20 naive) were enrolled. By 1 month, peak LH fell from 28.2 ± 19.97 (naive) to 0.8 ± 0.39 mIU/ml (P < 0.0001) and from 2.1 ± 2.15 (previously treated) to 0.5 ± 0.32 mIU/ml (P < 0.0056). Estradiol suppressed from 24.5 ± 22.27 (naive) to 5.9 ± 2.37 pg/ml (P = 0.0016) and remained suppressed in previously treated subjects, as did testosterone. Suppression was maintained throughout the study. No significant adverse events occurred. Conclusions: The subdermal histrelin implant achieves and maintains excellent suppression of peak LH and sex steroid levels for 1 yr in children with CPP. The treatment is well tolerated. Long-term studies are needed to confirm these results.

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