Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty

January 8, 2014 updated by: AbbVie (prior sponsor, Abbott)

A 36 Month, Multi-Center, Open-Label Extension Study to Evaluate the Safety of Leuprolide Acetate 11.25 mg and 30 mg Formulations in Children With Central Precocious Puberty

The purpose of this extension study is to determine if leuprolide acetate (11.25 mg and 30 mg) is safe in treating children with Central Precocious Puberty over a longer period of time (36 months).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study includes a 36-month Study Drug Treatment Period (3-month treatment cycles), and a Safety Follow-up Period (12 weeks following the Month 36 visit). Participants will receive a total of twelve injections of the same treatment they received in the lead-in study, L-CP07-167 (NCT00635817) either leuprolide acetate 11.25 mg or 30 mg depot formulation. Each injection will be administered 3 months apart for up to 36 months of treatment. Study visits will occur on Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30 and 33 (1st through the 12th leuprolide acetate depot injections, respectively), Month 36, and 12 weeks later for the Safety Follow-up Visit.

Study Type

Interventional

Enrollment (Actual)

72

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • Bayamon, Puerto Rico, 00960
        • Site Reference ID/Investigator# 23182
      • Ponce, Puerto Rico, 00717-2116
        • Site Reference ID/Investigator# 21721
      • Rio Piedras, Puerto Rico, 00935
        • Site Reference ID/Investigator# 25908
      • San Juan, Puerto Rico, 00936-8344
        • Site Reference ID/Investigator# 23082
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Site Reference ID/Investigator# 13521
    • California
      • Long Beach, California, United States, 90806
        • Site Reference ID/Investigator# 14922
      • Los Angeles, California, United States, 90027
        • Site Reference ID/Investigator# 26043
      • San Diego, California, United States, 92123
        • Site Reference ID/Investigator# 20802
    • Colorado
      • Greenwood Village, Colorado, United States, 80111
        • Site Reference ID/Investigator# 22425
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Site Reference ID/Investigator# 18181
      • Pensacola, Florida, United States, 32504
        • Site Reference ID/Investigator# 26364
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Site Reference ID/Investigator# 26983
    • Louisiana
      • Shreveport, Louisiana, United States, 71130-3932
        • Site Reference ID/Investigator# 20821
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Site Reference ID/Investigator# 23643
      • St. Paul, Minnesota, United States, 55102
        • Site Reference ID/Investigator# 23502
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Site Reference ID/Investigator# 14121
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Site Reference ID/Investigator# 23802
      • Tulsa, Oklahoma, United States, 74135
        • Site Reference ID/Investigator# 13324
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Site Reference ID/Investigator# 16506
    • Washington
      • Seattle, Washington, United States, 98104
        • Site Reference ID/Investigator# 14024

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subject completed the Treatment Period of the lead-in study, L-CP07-167 (NCT00635817), and has documented luteinizing hormone suppression as evidenced by peak-stimulated luteinizing hormone <4 mIU/mL at the Month 6 study visit of the lead-in study.
  • Demonstrated suppression of the physical signs of puberty at Month 6 of the lead-in study.
  • Subject is expected to receive at least 12 months of therapy to treat Central Precocious Puberty after study entry.
  • In general good health with no uncontrolled, clinically significant disease which would interfere with bone maturation or mask the objectives of this protocol as assessed by the investigator.

Exclusion Criteria:

  • Incomplete precocious puberty, peripheral precocious puberty or evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid and gonadal function (other than premature secretion of gonadotropins) not adequately controlled, unstable intracranial tumors except hamartoma.
  • Bone age ≥14 years for girls and ≥15 years for boys (based on the Month 6 lead in study, L-CP07-167, radiographic results).
  • Has an abnormal laboratory value suggesting a clinically significant underlying disease or condition.
  • Chronic illness requiring treatment that may interfere with growth, ie, chronic steroid use, renal failure, moderate to severe scoliosis.
  • Current therapy with medroxyprogesterone acetate.
  • Current therapy with growth hormone.
  • Current therapy with insulin-like growth factor-1 (IGF-1).
  • Current use of an estrogen preparation.
  • Any concomitant medical condition that, in the opinion of the investigator, may expose a subject to an unacceptable level of safety risk or that affects subject compliance.
  • Subject has a positive pregnancy test.

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Leuprolide Acetate 3M Depot 11.25 mg
Twelve intramuscular injections of leuprolide acetate for depot suspension 11.25 mg administered 3 months (3M) apart.
Drug: Leuprolide Acetate 3 Month Depot
Other Names:
  • Lupron
  • ABT-818
  • Leuprorelin acetate
Experimental: Leuprolide Acetate 3M Depot 30 mg
Twelve intramuscular injections of leuprolide acetate for depot suspension 30 mg administered 3 months apart.
Drug: Leuprolide Acetate 3 Month Depot
Other Names:
  • Lupron
  • ABT-818
  • Leuprorelin acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone
Time Frame: Day 1, Months 6, 12, 24, and 36
Luteinizing Hormone (LH) suppression is defined as peak-stimulated LH < 4 mIU/mL. Peak-stimulated LH refers to the maximum LH concentration measured 30 and 60 minutes after a gonadotropin-releasing hormone agonist (GnRHa) stimulation test. Participants who failed suppression at previous visit and prematurely discontinued were counted as having failed future visits also. Final visit is the participant's last visit closest to Month 36.
Day 1, Months 6, 12, 24, and 36

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1)
Time Frame: Day 1, Months 3, 6, 9, 12, and 24

The percentage of female participants with suppression of basal estradiol to prepubertal levels, defined as estradiol < 20 pg/mL.

The estradiol assay was changed in June of 2010, and the lower limit of quantitation (LLOQ) was increased from 1 pg/mL to 10 pg/mL. This outcome measure reports data for assays performed before this change occurred, with an LLOQ of 1 pg/mL. Final visit is the participant's last visit closest to Month 36.
Day 1, Months 3, 6, 9, 12, and 24
Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2)
Time Frame: Months 6, 9, 12, 24, 30, and 36

The percentage of female participants with suppression of basal estradiol to prepubertal levels, defined as estradiol < 20 pg/mL.

The estradiol assay was changed in June of 2010, and the lower limit of quantitation (LLOQ) was increased from 1 pg/mL to 10 pg/mL. This outcome measure reports data for assays performed after this change occurred, with an LLOQ of 10 pg/mL. Final visit is the participant's last visit closest to Month 36.
Months 6, 9, 12, 24, 30, and 36
Percentage of Male Participants With Suppression of Basal Testosterone
Time Frame: Day 1, Months 3, 6, 9, 12, 24, 30, and 36
The percentage of male participants with suppression of basal testosterone to prepubertal levels, defined as testosterone < 30 ng/dL. Final visit is the participant's last visit closest to Month 36.
Day 1, Months 3, 6, 9, 12, 24, 30, and 36
Mean Peak-stimulated Luteinizing Hormone Concentration by Visit
Time Frame: Baseline of the lead-in study L-CP07-167, Day 1, Months 6, 12, 24, and 36
Peak-stimulated luteinizing hormone refers to the maximum luteinizing hormone concentration measured 30 and 60 minutes after a gonadotropin-releasing hormone agonist (GnRHa) stimulation test. Final visit is the participant's last visit closest to Month 36.
Baseline of the lead-in study L-CP07-167, Day 1, Months 6, 12, 24, and 36
Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development)
Time Frame: Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36
The percentage of female participants with suppression of breast development. Breast development was rated from Stage 1 (early development) through Stage 5 (full development) according to a modified Tanner Staging pictogram. Suppression of breast development is defined as regression or no progression of breast development from Baseline (of the lead-in study L-CP07-167) according to pubertal staging. Girls entering the study with fully developed breasts (Stage 5) were excluded from this analysis. Final visit is the participant's last visit closest to Month 36.
Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36
Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development)
Time Frame: Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36
The percentage of male participants with suppression of testicular volume and genital staging. Testicular volume was calculated from the length, width and height of each testicle measured by ultrasound. External genital development (testes and penis) was rated from Stage 1 (early development) through Stage 5 (full development) according to a modified Tanner Staging pictogram. Suppression is defined as regression or no progression in both testicular volume and genital staging from Baseline (of the lead-in study L-CP07-167) according to pubertal staging. Boys entering the study with fully developed genitals (Stage 5) were excluded from this analysis. Final visit is the participant's last visit closest to Month 36.
Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36
Change From Baseline in Growth Rate
Time Frame: Baseline (the 1 year prior to the start of treatment in the lead-in study), and Day 1, Months 6, 12, 18, 24, 30, and 36
Baseline growth rate was the growth rate in the one year prior to Day 1 of the lead-in study L-CP07-167. Growth rates were calculated as the ratio of the change in height to the change in chronological age with an approximate 6-month interval for Day 1, Months 6, 12, 18, 24, 30, 36 and the Final Treatment Visit.
Baseline (the 1 year prior to the start of treatment in the lead-in study), and Day 1, Months 6, 12, 18, 24, 30, and 36
Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age
Time Frame: Baseline (of the lead-in study L-CP07-167), and Day 1, Months 12, 24, and 36

Bone age was determined by left hand/wrist bone age radiographs that were evaluated using the Fels Method by a central reader. The ratio of change from Baseline in bone age (BA)/change from Baseline in chronological age (CA) was calculated using the following formula:

(BA at Post-baseline Treatment Visit - BA at Baseline) / (CA at Post-baseline Treatment Visit - CA at Baseline).
Baseline (of the lead-in study L-CP07-167), and Day 1, Months 12, 24, and 36

Collaborators and Investigators

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

Sponsor

AbbVie (prior sponsor, Abbott)

Investigators

  • Study Director: Peter Bacher, MD, AbbVie

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

Helpful Links

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

December 1, 2008

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

April 24, 2008

First Submitted That Met QC Criteria

April 24, 2008

First Posted (Estimate)

April 28, 2008

Study Record Updates

Last Update Posted (Estimate)

January 9, 2014

Last Update Submitted That Met QC Criteria

January 8, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • L-CP07-177

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.

Subscribe