Efficacy, Safety, and Pharmacokinetics of Leuprolide Mesylate in Subjects With Central Precocious Puberty

Study Overview
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Brief Summary
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The study will evaluate if Leuprolide Mesylate is safe and effective in the treatment of subjects with central (gonadotropin-dependent) precocious puberty, when administered as two injections six months apart.

Detailed Description
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This is a multi-center, open-label, single-arm study. All subjects will be pediatric patients with central precocious puberty judged to be candidates for GnRH (gonadotropin releasing hormone) analog therapy, and all will receive two injections of FP-001 42 mg six-month apart in an unblinded fashion.

Official Title
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An Open-label, Single Arm, Multicenter, Phase III Study on the Efficacy, Safety, and Pharmacokinetics of FP-001 42 mg Controlled Release in Patients With Central (Gonadotropin-Dependent) Precocious Puberty (Casppian Study)

Conditions
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Puberty; Precocious, Central

Intervention / Treatment
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* Drug: Leuprolide Mesylate, Subcutaneous injection of 42 mg Leuprolide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged 2 to 8 years (inclusive) or males aged 2 to 9 years (inclusive). Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRHa treatment for CPP. Pubertal-type LH response at 60 minutes post GnRHa stimulation test before treatment initiation > 5 mIU/mL. Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development in females or testicular volume ≥ 4 mL in males. Willing and able to participate in the study. Difference between bone age (Greulich and Pyle method) and chronological age ≥ 1 year. Bone age < 13 years for girls and < 14 years for boys. Signed Institutional Review Board/Independent Ethics Committee (IRB/IEC)-approved informed consent form (ICF) by one or both parents (per IRB/IEC requirements), by the custodial parent(s) or by the legal guardian(s) (if required). Signed Assent by patients as per IRB/IEC requirements. Exclusion Criteria: Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion. This includes true CPP triggered by other conditions, such as congenital adrenal hyperplasia. Prior or current GnRH treatment for CPP. Non-progressing isolated premature thelarche. Presence of an unstable intracranial tumor or an intracranial tumor requiring neurosurgery or cerebral irradiation. Patients with hamartomas or adenomas not requiring surgery are eligible. Any other condition, chronic illness or treatment that, in the opinion of the Investigator, may interfere with growth or other study endpoints (e.g., chronic steroid use [except mild topical steroids], renal failure, diabetes, moderate to severe scoliosis, previously treated intracranial tumor). Prior or current therapy with medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1). Major medical or psychiatric illness that could interfere with study visits. Diagnosis of short stature (i.e., 2.25 standard deviations (SD) below the mean height for age). Positive urine pregnancy test. Known hypersensitivity to GnRH or related compounds. Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the patients to participate in the study. Any other condition(s) which could significantly interfere with Protocol compliance. Treatment with an investigational product within 5 half-lives of that product in prior clinical studies before the baseline visit (Day 0). Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions. Prior (within 6 months of Baseline (Day 0)) or current use of medications that, per Investigator opinion, have been associated with seizures or convulsions.

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: FP-001 42 mg<br>All subjects will be pediatric patients with central precocious puberty. They will be injected twice with a depot formulation containing 42 mg of Leuprolide. The first dose on day 0 the second dose on week 24 (six months apart). | Drug: Leuprolide Mesylate, Subcutaneous injection of 42 mg Leuprolide<br>* All subjects will be pediatric patients with central precocious puberty. They will be injected twice with a depot formulation containing 42 mg of Leuprolide. The first dose on day 0 the second dose on week 24 (six months apart).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Leuprolide Mesylate (FP-001 42 mg) | The percentage of patients with serum LH concentrations < 4 mIU/mL 60 minutes following an abbreviated GnRHa stimulation test at Visit 6 (Week 24). | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of FP-001 42 mg on bone age progression | Evaluate the changes in bone age progression from the baseline to Weeks 24 and 48 using centralized analysis of wrist x-ray | 24 and 48 weeks | 
| Effect of FP-001 42 mg on growth rate | Evaluate the changes in growth rate and bone age advancement relative to chronological age from baseline to end of study using height in meters | 48 weeks | 
| Effect of FP-001 42 mg on physical signs of puberty | Evaluate the change in physical signs of puberty as measure by Tanner stages from baseline to end of study | 48 weeks | 
| Effect of FP-001 42 mg on suppression of physical signs of puberty | Evaluate the percentage of patients with suppression of physical signs of puberty | 48 weeks | 
| Acute-On-Chronic (AOC) phenomenon of serum testosterone and LH | Evaluate The proportion of subjects exhibiting acute-on-chronic phenomenon (i.e., related to the second dose of FP-001 42 mg) | 48 weeks |