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Study of Lupron Depot In The Treatment of Central Precocious Puberty

Primary Purpose

Puberty, Precocious

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Lupron (leuprolide acetate)
Sponsored by
Abbott
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Puberty, Precocious focused on measuring CPP, central precocious puberty, pediatrics, suppression of LH, Lupron, leuprolide acetate, depot formulation, GnRHa, GnRH agonist, GNRH analog, LH, Tanner staging

Eligibility Criteria

undefined - 10 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Clinical diagnosis of isosexual central precocious puberty with onset of Tanner scores of Stage II for breast or pubic hair earlier than age 8.0 years in girls or Stage II for pubic hair or genitalia earlier than 9.0 years in boys.
  • Confirmation of diagnosis by a pubertal response to a gonadotropin-releasing hormone (GnRH) stimulation test (LH > 10 U/L at baseline).
  • Chronological age less than 9.0 years in girls or less than 10.0 years in boys at time of first dosing.
  • Bone age advanced at least 1 year beyond the chronological age at entry into the study.
  • The condition may be idiopathic or secondary to another lesion. If secondary, therapy of the primary condition will have been undertaken and stabilized.
  • No evidence of abnormal pituitary, adrenal, thyroid and gonadal function except for premature secretion of gonadotropins.

Exclusion Criteria:

  • Irradiation to the central nervous system.
  • Prior therapy with medroxyprogesterone acetate and/or with any GnRH analog (including prior treatment with daily subcutaneous and depot formulations of leuprolide acetate).

Sites / Locations

  • Site Reference ID/Investigator# 46673
  • Site Reference ID/Investigator# 46671
  • Site Reference ID/Investigator# 14921
  • Site Reference ID/Investigator# 14343
  • Site Reference ID/Investigator# 14341
  • Site Reference ID/Investigator# 14342
  • Site Reference ID/Investigator# 46672
  • Site Reference ID/Investigator# 46668
  • Site Reference ID/Investigator# 14344

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Breast Development in Females)
Suppression of clinical sexual characteristics was defined as regression (improvement) or no progression of breast development in females. Tanner staging is a scale of physical development that defines primary and secondary sex characteristics including size of breasts. The final visit occurred at a mean age +/- SD of 11.05 +/- 1.14 years (range, 6.96 to 12.95 years).
Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Genital Development in Males)
Suppression of clinical sexual characteristics was defined as regression (improvement) or no progression of genital development in males. Tanner staging is a scale of physical development that defines primary and secondary sex characteristics including size of genitals. The final visit occurred at a mean age +/- SD of 12.35 +/-1.35 years (range, 10.71 to 14.07 years).

Secondary Outcome Measures

Mean Peak Stimulated Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Concentrations
Mean peak stimulated visit LH and FSH concentrations were assessed according to the DELFIA (registered trademark) assay. The final visit for measurement of both hormone concentrations occurred at a mean age +/- SD of 11.13 +/- 1.23 (range, 6.73 to 14.07) years.
Mean Stimulated Estradiol Concentrations in Females
Mean estradiol concentrations were assessed according to the DELFIA (registered trademark) assay. The lower limit of quantitation for estradiol is 5 pg/mL and measurements below this limit are given a value of 5 pg/mL. The final visit for measurement estradiol concentrations occurred at a mean age +/- SD of 10.93 +/- 1.27 (range, 5.59 to 13.24) years.
Mean Stimulated Testosterone Concentrations in Males
Mean stimulated testosterone concentrations were assessed according to the DELFIA (registered trademark) assay. The final visit for measurement of testosterone occurred at a mean age +/- SD of 12.34 +/- 1.16 (range, 11.14 to 14.07) years.
Mean Ratio of Bone Age to Chronological Age
Bone age was determined by radiography of the wrist according to the Fels Method. The mean ratio of bone age to chronological age provides information about the slowing of bone age progression. A score = 1 indicates that bone age is equal to chronological age.

Full Information

First Posted
April 15, 2008
Last Updated
April 8, 2011
Sponsor
Abbott
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1. Study Identification

Unique Protocol Identification Number
NCT00660010
Brief Title
Study of Lupron Depot In The Treatment of Central Precocious Puberty
Official Title
Study of Lupron Depot In The Treatment of Central Precocious Puberty
Study Type
Interventional

2. Study Status

Record Verification Date
April 2011
Overall Recruitment Status
Completed
Study Start Date
January 1991 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Abbott

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine if Lupron (leuprolide acetate) is safe and effective in treating children with Central Precocious Puberty (CPP), and to assess long term effects of leuprolide acetate treatment after therapy is discontinued.
Detailed Description
This study includes a Prestudy Period; a treatment period where subjects will receive treatment every 4 weeks until the initiation of puberty (age 12 for males and age 11 for females); a follow-up period where subjects will be observed every 6 months until physical and laboratory observations are at pubertal levels, then every 12 months for 5 years; lastly a final follow-up questionnaire is given to all subjects when they are at least 18 years old. At the treatment visits, efficacy assessments are Tanner staging (suppression of breast development in females and genital development in males), gonadotropins (LH and FSH), sex steroids (estradiol in females and testosterone in males), ratio of bone age to chronological age, adult height compared to a standard population and predicted mature height, and age and time to regular menses in females. This protocol will also capture data from the final questionnaire about female reproductive status at adulthood including the presence of regular menses and number of pregnancies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Puberty, Precocious
Keywords
CPP, central precocious puberty, pediatrics, suppression of LH, Lupron, leuprolide acetate, depot formulation, GnRHa, GnRH agonist, GNRH analog, LH, Tanner staging

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Lupron (leuprolide acetate)
Other Intervention Name(s)
Lupron
Intervention Description
Leuprolide acetate was administered monthly by intramuscular injection starting at 300 mcg/kg with adjustments of 3.75 mg upward, at subsequent clinic visits based on physical and laboratory parameters. Dosing continued until NDA was approved, or until subject no longer required leuprolide acetate to treat CPP.
Primary Outcome Measure Information:
Title
Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Breast Development in Females)
Description
Suppression of clinical sexual characteristics was defined as regression (improvement) or no progression of breast development in females. Tanner staging is a scale of physical development that defines primary and secondary sex characteristics including size of breasts. The final visit occurred at a mean age +/- SD of 11.05 +/- 1.14 years (range, 6.96 to 12.95 years).
Time Frame
Week 4, Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
Title
Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Genital Development in Males)
Description
Suppression of clinical sexual characteristics was defined as regression (improvement) or no progression of genital development in males. Tanner staging is a scale of physical development that defines primary and secondary sex characteristics including size of genitals. The final visit occurred at a mean age +/- SD of 12.35 +/-1.35 years (range, 10.71 to 14.07 years).
Time Frame
Week 4, Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
Secondary Outcome Measure Information:
Title
Mean Peak Stimulated Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Concentrations
Description
Mean peak stimulated visit LH and FSH concentrations were assessed according to the DELFIA (registered trademark) assay. The final visit for measurement of both hormone concentrations occurred at a mean age +/- SD of 11.13 +/- 1.23 (range, 6.73 to 14.07) years.
Time Frame
Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
Title
Mean Stimulated Estradiol Concentrations in Females
Description
Mean estradiol concentrations were assessed according to the DELFIA (registered trademark) assay. The lower limit of quantitation for estradiol is 5 pg/mL and measurements below this limit are given a value of 5 pg/mL. The final visit for measurement estradiol concentrations occurred at a mean age +/- SD of 10.93 +/- 1.27 (range, 5.59 to 13.24) years.
Time Frame
Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
Title
Mean Stimulated Testosterone Concentrations in Males
Description
Mean stimulated testosterone concentrations were assessed according to the DELFIA (registered trademark) assay. The final visit for measurement of testosterone occurred at a mean age +/- SD of 12.34 +/- 1.16 (range, 11.14 to 14.07) years.
Time Frame
Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
Title
Mean Ratio of Bone Age to Chronological Age
Description
Bone age was determined by radiography of the wrist according to the Fels Method. The mean ratio of bone age to chronological age provides information about the slowing of bone age progression. A score = 1 indicates that bone age is equal to chronological age.
Time Frame
Week 24 and Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
Other Pre-specified Outcome Measures:
Title
Posttreatment Height (ht.) Compared to Standard Population and as Predicted From Ht. at Baseline (BL)
Description
Height was measured by stadiometer and was standardized for age according to standard growth charts. A standardized score of 0 indicated a mean ht. equivalent to mean of a standard population from 2000 CDC standardized ht. charts. Height gain was calculated as ht. - predicted ht. from the Bayley-Pinneau method on the basis of bone age at baseline. Final adult ht. was determined by measurement at final adult ht., if available, or by ht. collected during the follow-up period associated with a growth velocity <1 cm/year or a bone age >14 yrs in females or >15 yrs in males.
Time Frame
Final ht. (measured or provided for final questionnaire in subjects >= 18 years of age) or near final adult ht. (<1 cm/year or bone age > 14 years for females or > 15 years for males)
Title
Mean Time to or Mean Age at Regular Menses in Females After Treatment
Description
Regular menses was defined as 3 or more consecutive days of menstrual-like bleeding and was defined by the investigator's clinical judgment.
Time Frame
Posttreatment during the follow-up period (subjects observed every 6 months until physical and laboratory observations are at pubertal levels)
Title
Number of Female Subjects Who Reported Regular Menses at Adulthood
Description
Subjects were required to complete final adult questionnaire to provide information on adult reproductive function. Regular menses was defined as 3 or more consecutive days of menstrual-like bleeding.
Time Frame
Posttreatment data were collected from the final adult questionnaire (subjects >= 18 years of age)
Title
Number of Subjects Who Reported Pregnancies at Final Questionnaire
Description
The final questionnaire was completed by 20 females who were at least 18 years of age. The subjects reported on total number of pregnancies resulting in live births or number of miscarriages (spontaneous or elective) and whether the subject was currently pregnant.
Time Frame
Posttreatment data were collected from the final adult questionnaire (subjects >= 18 years of age)
Title
Number of Pregnancies Reported by Subjects at Final Questionnaire
Description
The final questionnaire was completed by 20 female subjects who were at least 18 years of age. The total number of pregnancies were reported.
Time Frame
Posttreatment data were collected from the final adult questionnaire (subjects >= 18 years of age)

10. Eligibility

Sex
All
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Clinical diagnosis of isosexual central precocious puberty with onset of Tanner scores of Stage II for breast or pubic hair earlier than age 8.0 years in girls or Stage II for pubic hair or genitalia earlier than 9.0 years in boys. Confirmation of diagnosis by a pubertal response to a gonadotropin-releasing hormone (GnRH) stimulation test (LH > 10 U/L at baseline). Chronological age less than 9.0 years in girls or less than 10.0 years in boys at time of first dosing. Bone age advanced at least 1 year beyond the chronological age at entry into the study. The condition may be idiopathic or secondary to another lesion. If secondary, therapy of the primary condition will have been undertaken and stabilized. No evidence of abnormal pituitary, adrenal, thyroid and gonadal function except for premature secretion of gonadotropins. Exclusion Criteria: Irradiation to the central nervous system. Prior therapy with medroxyprogesterone acetate and/or with any GnRH analog (including prior treatment with daily subcutaneous and depot formulations of leuprolide acetate).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristof Chwalisz, MD
Organizational Affiliation
Abbott
Official's Role
Study Director
Facility Information:
Facility Name
Site Reference ID/Investigator# 46673
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Site Reference ID/Investigator# 46671
City
San Francisco
State/Province
California
ZIP/Postal Code
94122
Country
United States
Facility Name
Site Reference ID/Investigator# 14921
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Site Reference ID/Investigator# 14343
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Site Reference ID/Investigator# 14341
City
St. Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Site Reference ID/Investigator# 14342
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Site Reference ID/Investigator# 46672
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Site Reference ID/Investigator# 46668
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
Site Reference ID/Investigator# 14344
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21860633
Citation
Lee PA, Neely EK, Fuqua J, Yang D, Larsen LM, Mattia-Goldberg C, Chwalisz K. Efficacy of Leuprolide Acetate 1-Month Depot for Central Precocious Puberty (CPP): Growth Outcomes During a Prospective, Longitudinal Study. Int J Pediatr Endocrinol. 2011;2011(1):7. doi: 10.1186/1687-9856-2011-7. Epub 2011 Jul 12.
Results Reference
derived

Learn more about this trial

Study of Lupron Depot In The Treatment of Central Precocious Puberty

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