Study of Lupron Depot In The Treatment of Central Precocious Puberty

Study Overview
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Brief Summary
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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
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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.

Official Title
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Study of Lupron Depot In The Treatment of Central Precocious Puberty

Conditions
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Puberty, Precocious

Intervention / Treatment
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* Drug: Lupron (leuprolide acetate)


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Lupron (leuprolide acetate)<br>* 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.<br>* Other names: Lupron;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CPP, central precocious puberty, pediatrics, suppression of LH, Lupron, leuprolide acetate, depot formulation, GnRHa, GnRH agonist, GNRH analog, LH, Tanner staging