Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty

Study Overview
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Brief Summary
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This study determines the effectiveness of leuprolide acetate 45 mg for injectable suspension for treatment of children with Central Precocious Puberty.

Detailed Description
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Leuprolide acetate is a GnRH agonist that inhibits pituitary gonadotropin secretion by binding to the GnRH receptors and blocking downstream hormone synthesis. The steady decrease in hormone synthesis (LH and FSH) leads to a suppression of testicular and ovarian steroidogenesis. In children with CPP, this steady decrease in hormone synthesis disrupts the progression of puberty.

Official Title
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An Open-label, Single Arm, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Leuprolide Acetate 45 mg for Injectable Suspension Controlled Release in Subjects With Central (Gonadotropin-Dependent) Precocious Puberty

Conditions
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Precocious Puberty, Central

Intervention / Treatment
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* Drug: Leuprolide Acetate 45 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females age 2 to 8 years (inclusive) or males age 2 to 9 years (inclusive) Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRH agonist treatment for CPP Pubertal-type LH response following an abbreviated GnRHa stimulation test before treatment initiation Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development in females or testicular volume ≥ 4 mL in males Difference between bone age (Greulich and Pyle method) and chronological age ≥ 1 year Exclusion Criteria: Gonadotropin-independent (peripheral) precocious puberty Prior or current GnRH treatment for CPP Prior or current therapy with medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1) Diagnosis of short stature (ie, 2.25 standard deviations (SD) below the mean height for age) Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 9 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Assigned Intervention<br>Leuprolide acetate 45 mg will be administered as a subcutaneous injection at 6-month intervals for the 12 month study period. | Drug: Leuprolide Acetate 45 mg<br>* Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months. | Luteinizing Hormone (LH) suppression is defined as peak-stimulated LH <4 IU/L. Peak stimulated LH refers to the maximum LH concentration measured 30 minutes after a gonadotropin-releasing hormone agonst (GnRHa) stimulation test. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels. | Percentage of subjects with suppressed serum LH concentrations(<4 IU/L) 30 minutes post GnRHa stimulation test at all assessed timepoints. | Week 12, Week 24, Week 36, and Week 48 | 
| Changes in Height Velocity (Growth Rate) | Changes in height velocity (growth rate) at all study timepoints after Screening to end of study. Growth velocity is defined for each visit as change from baseline / [(number of weeks since baseline)/52]. Week 48: Change from Week 24 growth velocity is defined as change from week 24 to week 48 / [(number of weeks since week 24)/52]. | Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48 | 
| Bone Age Ratio to Chronological Age at Time of Measurement | Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment. | Week 24 and Week 48 | 
| Percent Change From Baseline in Height | The percent change from baseline in height at each available post-baseline measurement. Percent change is defined as (((change from Baseline)/(Baseline)) x 100). | Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48 | 
| Tanner Scores: Boys - Development of External Genitalia | Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics. | Baseline, Week 12, Week 24, Week 36, and Week 48 | 
| Tanner Scores: Boys - Development of External Genitalia (Change From Baseline) | Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics. | Week 12, Week 24, Week 36, and Week 48 | 
| Tanner Scores: Boys and Girls - Pubic Hair | Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics. | Baseline, Week 12, Week 24, Week 36, and Week 48 | 
| Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline) | Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics. | Week 12, Week 24, Week 36, and Week 48 | 
| Tanner Scores: Girls - Breast Development | Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics. | Baseline, Week 12, Week 24, Week 36, and Week 48 | 
| Tanner Scores: Girls - Breast Development (Change From Baseline) | Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics. | Week 12, Week 24, Week 36, and Week 48 |