Study of Lupron Depot In The Treatment of Central Precocious Puberty

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Puberty, Precocious	Drug: Lupron (leuprolide acetate)	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	55 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Study of Lupron Depot In The Treatment of Central Precocious Puberty
Study Start Date :	January 1991
Actual Primary Completion Date :	April 2009
Actual Study Completion Date :	April 2009

Arms and Interventions

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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 Name: Lupron

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Breast Development in Females) [ Time Frame: Week 4, Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit ]
   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).
2. Percentage of Subjects (n/N) With Suppression of Clinical Sexual Characteristics According to Tanner Staging (Genital Development in Males) [ Time Frame: Week 4, Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit ]
   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 :

1. Mean Peak Stimulated Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) Concentrations [ Time Frame: Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit ]
   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.
2. Mean Stimulated Estradiol Concentrations in Females [ Time Frame: Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit ]
   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.
3. Mean Stimulated Testosterone Concentrations in Males [ Time Frame: Baseline, Weeks 4, 12, 24, 48 (Year 1), yearly for 5 years (Week 240), and Final Visit ]
   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.
4. Mean Ratio of Bone Age to Chronological Age [ Time Frame: Week 24 and Week 48 (Year 1), yearly for 5 years (Week 240), and Final Visit ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	up to 10 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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).

Contacts and Locations

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Locations

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

Sponsors and Collaborators

Abbott

Investigators

Study Director:	Kristof Chwalisz, MD	Abbott

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Kristof Chwalisz, MD, PhD Therapeutic Area Head, Abbott
ClinicalTrials.gov Identifier:	NCT00660010 History of Changes
Other Study ID Numbers:	M90-516
First Posted:	April 17, 2008
Results First Posted:	July 20, 2010
Last Update Posted:	April 12, 2011
Last Verified:	April 2011

Keywords provided by Abbott:

central precocious puberty; CPP; pediatrics; suppression of LH; Lupron; leuprolide acetate	depot formulation; GnRHa; GnRH agonist; GNRH analog; LH; Tanner staging

Additional relevant MeSH terms:

Puberty, Precocious; Gonadal Disorders; Endocrine System Diseases; Leuprolide; Fertility Agents, Female	Fertility Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents