Study of Lupron Depot In The Treatment of Central Precocious Puberty

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.

Study Overview

• Status: Completed
• Conditions: Puberty, Precocious
• Intervention / Treatment: Drug: Lupron (leuprolide acetate)

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.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Site Reference ID/Investigator# 46673
  • California
    • San Francisco, California, United States, 94122
      • Site Reference ID/Investigator# 46671
    • Stanford, California, United States, 94305
      • Site Reference ID/Investigator# 14921
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Site Reference ID/Investigator# 14343
  • Florida
    • St. Petersburg, Florida, United States, 33701
      • Site Reference ID/Investigator# 14341
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Site Reference ID/Investigator# 14342
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Site Reference ID/Investigator# 46672
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Site Reference ID/Investigator# 46668
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Site Reference ID/Investigator# 14344

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Lupron (leuprolide acetate); 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.; Other Names: Lupron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Week 4, Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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).	Week 4, Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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.	Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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.	Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit
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.	Week 24 and Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Posttreatment Height (ht.) Compared to Standard Population and as Predicted From Ht. at Baseline (BL)	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.	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)
Mean Time to or Mean Age at Regular Menses in Females After Treatment	Regular menses was defined as 3 or more consecutive days of menstrual-like bleeding and was defined by the investigator's clinical judgment.	Posttreatment during the follow-up period (subjects observed every 6 months until physical and laboratory observations are at pubertal levels)
Number of Female Subjects Who Reported Regular Menses at Adulthood	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.	Posttreatment data were collected from the final adult questionnaire (subjects >= 18 years of age)
Number of Subjects Who Reported Pregnancies at Final Questionnaire	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.	Posttreatment data were collected from the final adult questionnaire (subjects >= 18 years of age)
Number of Pregnancies Reported by Subjects at Final Questionnaire	The final questionnaire was completed by 20 female subjects who were at least 18 years of age. The total number of pregnancies were reported.	Posttreatment data were collected from the final adult questionnaire (subjects >= 18 years of age)

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Kristof Chwalisz, MD, Abbott

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 1991
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: April 15, 2008
• First Submitted That Met QC Criteria: April 15, 2008
• First Posted (Estimate): April 17, 2008

Study Record Updates

• Last Update Posted (Estimate): April 12, 2011
• Last Update Submitted That Met QC Criteria: April 8, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: pediatrics; GnRH agonist; LH; GnRHa; Lupron; CPP; central precocious puberty; leuprolide acetate; depot formulation; suppression of LH; GNRH analog; Tanner staging
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: M90-516