Histrelin Subcutaneous Implant in Children With Central Precocious Puberty

December 15, 2020 updated by: Endo Pharmaceuticals

Phase III, Open-Label Study to Evaluate Efficacy and Safety of Histrelin Subdermal Implant in Children With Central Precocious Puberty

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 10 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Histrelin Subcutaneous Implant (50 mg)
Subcutaneous implant designed to deliver histrelin continously for 12 months.
Drug: Histrelin Subcutaneous Implant
histrelin subcutaneous 50 mg implant
Other Names:
  • Supprelin LA
  • implant therapy
  • histrelin implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Luteinizing Hormone (LH)
Time Frame: Baseline - 6 Months Post Last Implant
The suppression of gonadotropins (luteinizing hormone and follicle stimulating hormone) and gonadal sex steroids (estrogen in girls and testosterone in boys, respectively) on treatment.(LH suppression is defined as a peak LH < 4 mIU/mL following stimulation with the GnRH analog).
Baseline - 6 Months Post Last Implant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Follicle Stimulating Hormone (FSH)
Time Frame: Baseline - 6 Month Post Last Implant
The suppression of gonadotropins (luteinizing hormone and follicle stimulating hormone) and gonadal sex steroids (estrogen in girls and testosterone in boys, respectively) on treatment.(LH suppression is defined as a peak LH < 4 mIU/mL following stimulation with the GnRH analog).
Baseline - 6 Month Post Last Implant
Testosterone
Time Frame: Baseline - 12 Months Post Last Implant
Long-term treatment with histrelin acetate suppresses the LH response to GnRH causing LH levels to decrease to prepubertal levels within 1 month of treatment. As a result, serum concentrations of sex steroids (estrogen or testosterone) also decrease. Testosterone suppression is defined as serum testosterone < 30.0 ng/dL (0.8 nmol/L) in boys following the induction of suppression. One black female participant age 8.9 years old had a testosterone value of 11ng/dL at visit 4 (month 6).
Baseline - 12 Months Post Last Implant
DHEA Sulfate
Time Frame: Baseline - 36 Months Post Last Implant
DHEA=Dehydroepiandrosterone
Baseline - 36 Months Post Last Implant
Estradiol (MS)
Time Frame: Month 36 - 36 Months Post Last Implant
Long-term treatment with histrelin acetate suppresses the LH response to GnRH causing LH levels to decrease to prepubertal levels within 1 month of treatment. As a result, serum concentrations of sex steroids (estrogen or testosterone) also decrease. Estradiol suppression is defined as serum estradiol in the assay specific range < 20 pg/mL (73 pmol/L) in girls following the induction of suppression.
Month 36 - 36 Months Post Last Implant
Estradiol (RIA)
Time Frame: Baseline - Month 24
Long-term treatment with histrelin acetate suppresses the LH response to GnRH causing LH levels to decrease to prepubertal levels within 1 month of treatment. As a result, serum concentrations of sex steroids (estrogen or testosterone) also decrease. Estradiol suppression is defined as serum estradiol in the assay specific range < 20 pg/mL (73 pmol/L) in girls following the induction of suppression.
Baseline - Month 24
Average Number of Implants Received
Time Frame: 12 months
There were 2 implants received that were not removed during the study and were excluded from this analysis due to unknown duration of treatment.
12 months
Average Mean Implant Duration by Subject
Time Frame: 12 Months
There were 2 implants received that were not removed during the study and were excluded from this analysis due to unknown duration of treatment.
12 Months
Summary of EN3326 Implantation and Explantations
Time Frame: Day 1 - Month 60
Once the female participants reached 11 years of age and the male participants reached 12 years of age or the investigator determined that subjects no longer required hormone suppression, participants underwent final explantation and were eligible to continue into an optional Long Term Follow Up Phase (Post Implant Treatment Phase) for up to 5 years. The purpose of the optional Long Term Follow Up Phase was to collect additional medical and developmental information, such as onset of menses and final adult height after hormone suppression was discontinued.
Day 1 - Month 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Endo Pharmaceuticals

Investigators

  • Principal Investigator: Erica A Eugster, MD, Indiana University School of Medicine, 705 Riley Hosp Dr, Rm 5960 Indianapolis, IN 46202

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2004

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

October 22, 2008

First Submitted That Met QC Criteria

October 23, 2008

First Posted (Estimate)

October 24, 2008

Study Record Updates

Last Update Posted (Actual)

January 8, 2021

Last Update Submitted That Met QC Criteria

December 15, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EN3326-300Former03-CPP-HIS-300

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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