Clinical trial NCT00779103: Histrelin Subcutaneous Implant in Children With Central Precocious Puberty
Official title: Phase III, Open-Label Study to Evaluate Efficacy and Safety of Histrelin Subdermal Implant in Children With Central Precocious Puberty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Central Precocious Puberty
Keywords: puberty
precocious puberty
early puberty
early onset puberty
histrelin
histrelin subcutaneous implant
implant therapy
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-10-24
Enrollment: 36
Sex: ALL
Minimum age (years): 2
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to follow and collect additional medical and developmental information on children after histrelin subcutaneous implant therapy is discontinued.

Detailed description: Thirty-two (32) patients will receive a histrelin subdermal implant under the anesthesia deemed appropriate by the administering physician. Ten-twelve (10-12) sites will enroll 2-3 patients per site. It is anticipated that half the patients will be receiving GnRH analog treatment and the other half will be treatment naïve. All patients will undergo selective PK sampling post-implantation to assess histrelin profile. At 12 months, provided that the patient continues to meet the safety and efficacy parameters, the original implant will be removed and the patient can receive a new implant. At 13 months, patients who receive new implants will be evaluated at the study site and administratively transferred to the initial extension study. At Month 24), the implants inserted at Month 12 will be removed. At this time, patients who have completed the initial extension study and who wish to continue therapy with the histrelin implant will be eligible to receive a new (ie, third) implant and to enter an additional 12-month extended access phase at the discretion of the investigator. At Month 36, the implants inserted at Month 24 for the Extended Access Phase will be removed. At this time, patients who have completed the Extended Access Phase and who wish to continue therapy with the histrelin implant will be eligible to receive a new (ie, fourth) implant and to enter the Long Term Extended Access Phase (referred to as the Implant Treatment Phase) at the discretion of the investigator. The purpose of this phase is to provide patients with the opportunity to continue to receive a new implant at the end of each 12-month period until the patient no longer requires hormone suppression. Once implant therapy is discontinued, all patients are eligible to enter the Long Term Follow Up Phase (Post Implant Phase) of the study.

Eligibility criteria: Inclusion Criteria:

* Pre-treated or treatment naive patients with gonadotropin-dependent precocious puberty
* Pre-treatment pubertal type response of LH to a stndard GnRH stimulation test before initiation of treatment

Exclusion Criteria:

* Children who are less than 2 years of age at enrollment
* Children whose chronological age is greater than 8 years (naive) and 10 years (pre-treated) for girls or 9 years (naive) and 11 years (pre-treated) for boys at the onset of the study

Primary outcomes:
measure: Luteinizing Hormone (LH)
timeFrame: Baseline - 6 Months Post Last Implant
Secondary outcomes:
measure: Follicle Stimulating Hormone (FSH)
timeFrame: Baseline - 6 Month Post Last Implant
measure: Testosterone
timeFrame: Baseline - 12 Months Post Last Implant
measure: DHEA Sulfate
timeFrame: Baseline - 36 Months Post Last Implant
measure: Estradiol (MS)
timeFrame: Month 36 - 36 Months Post Last Implant
measure: Estradiol (RIA)
timeFrame: Baseline - Month 24
measure: Average Number of Implants Received
timeFrame: 12 months
measure: Average Mean Implant Duration by Subject
timeFrame: 12 Months
measure: Summary of EN3326 Implantation and Explantations
timeFrame: Day 1 - Month 60
Other outcomes:
Locations:
Study officials:
affiliation: Indiana University School of Medicine, 705 Riley Hosp Dr, Rm 5960 Indianapolis, IN 46202
name: Erica A Eugster, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Silverman LA, Neely EK, Kletter GB, Lewis K, Chitra S, Terleckyj O, Eugster EA. Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial. J Clin Endocrinol Metab. 2015 Jun;100(6):2354-63. doi: 10.1210/jc.2014-3031. Epub 2015 Mar 24.
citation: Neely EK, Silverman LA, Geffner ME, Danoff TM, Gould E, Thornton PS. Random unstimulated pediatric luteinizing hormone levels are not reliable in the assessment of pubertal suppression during histrelin implant therapy. Int J Pediatr Endocrinol. 2013 Dec 2;2013(1):20. doi: 10.1186/1687-9856-2013-20.