Efficacy, Safety, and Pharmacokinetics (PK) of Triptorelin 6-month Formulation in Patients With Central Precocious Puberty

Study Overview
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Brief Summary
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The study will investigate the efficacy, safety and pharmacokinetics of triptorelin 22.5 mg 6-month formulation in 44 patients suffering from central precocious puberty. The total study duration per patient will be 12 months (48 weeks).

Official Title
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An Open-label, Non-comparative, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Triptorelin Pamoate (Embonate) 22.5 mg 6-month Formulation in Patients Suffering From Central (Gonadotropin-dependent) Precocious Puberty

Conditions
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Central Precocious Puberty

Intervention / Treatment
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* Drug: Triptorelin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Onset of development of sex characteristics before 8 and 9 years in girls and boys, respectively (breast development in girls or testicular enlargement in boys according to the Tanner method), and candidate to receive at least 12 months of GnRH agonist therapy after study entry. Aged 2-8 years inclusive (i.e. < 9 years) for girls and 2-9 years inclusive (i.e. < 10 years) for boys at initiation of triptorelin treatment. Initiation of triptorelin treatment at the latest 18 months after onset of the first signs of precocious puberty. Difference (Δ) bone age (Greulich and Pyle method) - chronological age ≥ 1 year. Pubertal-type LH response 30 minutes following a GnRH agonist stimulation test before treatment initiation (leuprolide acetate 20 μg/kg SC) ≥ 6 IU/L. Clinical evidence of puberty, defined as Tanner Staging ≥ 2 for breast development for girls and testicular volume ≥ 4 mL (cc) for boys. Informed consent signed by one parent or both parents (as per local requirements), by the liable parent or by the legal guardian (when applicable); assent signed by the child if ≥ 7 years. Non-inclusion criteria: Gonadotropin-independent (peripheral) precocious puberty: extra pituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroid secretion. Non-progressing isolated premature thelarche. Presence of an unstable intracranial tumour or an intracranial tumour requiring neurosurgery or cerebral irradiation. Patients with hamartomas not requiring surgery are eligible. Evidence of renal (creatinine > 2 x ULN) or hepatic impairment (bilirubin or ASAT > 3 x ULN). Any other condition or chronic illness or treatment possibly interfering 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 tumour). Prior or current therapy with a GnRH agonist, 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 SD below the mean height for age. Positive pregnancy test. Known hypersensibility to any of the test materials or related compounds. Use of anticoagulants (heparin and coumarin derivatives).

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: Triptorelin<br>Triptorelin 22.5 mg, intramuscular (IM), at Day 1 and Day 169 | Drug: Triptorelin<br>* Powder and solution for solution for injection<br>* Other names: Trelstar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Children With Luteinizing Hormone (LH) Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Month 6 | This is a lab test to see what percentage of participants were returned to normal before-puberty levels at Month 6. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Children With LH Suppression to Prepubertal Levels 30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 9 and 12 | This is a lab test to see what percentage of children were returned to normal before-puberty levels by the drug at each time point. | at Months 1, 2, 3, 9 and 12 | 
| Percentage of Children Maintaining LH Suppression at Prepubertal Levels 30 Minutes After Leuprolide Stimulation From Month 6 to 12 | This is a lab test to see what percentage of children stayed at the normal before-puberty level from month 6 to month 12. | from Month 6 to 12 | 
| Percentage of Children With LH Suppression (LH ≤ 4 IU/L)30 Minutes After Leuprolide Stimulation at Months 1, 2, 3, 6, 9 and 12 | This is a lab test to see what percentage of children were returned to lower than normal before-puberty levels by the drug at each time point. | at Months 1, 2, 3, 6, 9 and 12 | 
| Percentage of Children Maintaining LH Suppression at </= 4 IU/L 30 Minutes After Leuprolide Stimulation From Month 6 to 12 | This is a lab test to see what percentage of children stayed at the lower than normal before-puberty level from month 6 to month 12. | from Month 6 to 12 | 
| Change From Baseline in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) at Months 1, 2, 3, 6, 9, and 12 |  | Baseline to Months 1, 2, 3, 6, 9, and 12 | 
| Change From Baseline in Estradiol Levels at Months 1, 2, 3, 6, 9, and 12 |  | Baseline to Months 1, 2, 3, 6, 9, and 12 | 
| Change From Baseline in Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 |  | Baseline to Months 1, 2, 3, 6, 9, and 12 | 
| Percentage of Children With Prepubertal Estradiol or Testosterone Levels at Months 1, 2, 3, 6, 9, and 12 |  | at Months 1, 2, 3, 6, 9, and 12 | 
| Percentage of Children Without Higher Basal LH and Estradiol or Testosterone |  | at 2 days after second triptorelin injection (Day 171) | 
| Change From Baseline in Height-for-age Z-score Per 2000 CDC Growth Charts at Months 6 and 12 |  | Baseline to Months 6 and 12 | 
| Change From Baseline in Height-for-age Percentile Per 2000 CDC Growth Charts at Months 6 and 12 |  | Baseline to Months 6 and 12 | 
| Change From Baseline in Growth Velocity at Months 6 and 12 |  | Baseline to Months 6 and 12 | 
| Percentage of Participants Without Bone Age / Chronological Age Ratio Increase From Baseline at Months 6 and 12 |  | Baseline to Months 6 and 12 | 
| Percentage of Children Achieving Stabilization of Sexual Maturation at Months 6 and 12 |  | at Months 6 and 12 | 
| Percentage of Girls With Regression of Uterine Length Compared to Baseline at Months 6 and 12 |  | Baseline to Months 6 and 12 | 
| Percentage of Boys With Absence of Progression of Testis Volumes Compared to Baseline at Months 6 and 12 |  | Baseline to Months 6 and 12 |