Efficacy and Safety Study of Pamoate of Triptorelin in Children With Precocious Puberty

Study Overview
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Brief Summary
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The purpose of the study is to assess the efficacy of triptorelin 11.25 mg pamoate in the delay of premature onset of puberty in girls less than 9 years and boys less than 10 years. This is measured by assessing the proportion of children who have a suppressed Luteinizing Hormone (LH) response to Gonadotropin Releasing Hormone (GnRH) test performed 3 months after injection with triptorelin 11.25 mg.

Official Title
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Phase III, Multicentre, Non-comparative, Open and Single Stage Study to Assess the Efficacy and Safety of Pamoate of Triptorelin 11.25 MG in Children With Precocious Puberty

Conditions
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Precocious Puberty

Intervention / Treatment
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* Drug: Triptorelin pamoate 11.25mg (Decapeptyl® SR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria in the screening phase: Onset of sex characteristics (Tanner method) breast development in girls or testicular enlargement in boys before the age of 8 years in girls and 9 years in boys. Weight ≥ 20 kg. Inclusion Criteria in the treatment phase: Proven central precocious puberty defined as onset of sex characteristics development (according to Tanner method) diagnosed before the age of 8 years in girls and 9 years in boys. Age at evaluation less than 9 years for girls and 10 years for boys. A pubertal response of LH to GnRH test in both sexes (stimulated LH ≥ 5 IU/l). Difference Bone age (BA) (according to Greulich et Pyle method) - Chronological age (CA) > 1 year. Testosterone level ≥ 0.5 ng/ml in boys. Exclusion Criteria: Patient with a peripheral precocious puberty: extrapituitary secretion of gonadotropins or gonadotropin-independent gonadal or adrenal sex steroids secretion. Patient with a cerebral tumour requiring a neurosurgery or cerebral irradiation. Patient with a Body Weight ≥ 125% of the ideal weight for the height and age (growth curves). The patient has received a previous treatment with a GnRH analogue, or medroxyprogesterone or cyproterone acetate.
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 pamoate 11.25mg (Decapeptyl® SR)<br> | Drug: Triptorelin pamoate 11.25mg (Decapeptyl® SR)<br>* One intra muscular injection at day 1 and month 3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a GnRH-stimulated LH Level ≤3 IU/L |  | 3 months after the first injection of triptorelin pamoate 11.25 mg | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Whose Intravenous (i.v.) GnRH-stimulated LH Response Was ≤3 IU/L |  | Month 6 | 
| Follicle Stimulating Hormone (FSH) Level Following GnRH Test |  | Screening, month 3 and 6 | 
| Basal FSH Level |  | Month 0, 1, 2, 3, 4, 5, and 6 | 
| Basal LH Level |  | Month 0, 1, 2, 3, 4, 5 and 6 | 
| Number of Girls With Oestradiol Levels ≤ 20 pg/ml |  | Month 0, 1, 2, 3, 4, 5 and 6 | 
| Testosterone Level |  | Month 0, 3 and 6 | 
| Number of Girls With Inhibin B Levels < 6 pg/ml |  | Month 0, 3 and 6 | 
| Change From Screening in Pubertal Stage (Tanner Method) at Month 6 | Pubertal stage (graded from 1 to 5 for penis and breast development, graded from 1 to 6 for pubic hair development) according to the Tanner method was collected. A low stage (i.e. 1) corresponds to a pre-pubertal stage and a high stage (i.e. 5 or 6) to an adult stage. Any increase of grade was defined as 'increased' and no change in grade or a reduced grade was defined as 'stabilised or reduced'. | Between screening and month 6 | 
| Height Standard Deviation Score (SDS) | Standard deviation (SD) is a standard term used in growth studies and represents Standard Deviations calculated as the patient value minus the mean divided by the standard deviation. Standard Deviation Scores vary depending on the age and sex of the child. | Month 0, 3 and 6 | 
| Body Mass Index (BMI) SDS |  | Month 0, 3 and 6 | 
| Change From Baseline in Growth Velocity (GV) SDS at Month 6 | Change from baseline of GV was calculated as: GV at month 6 - GV at baseline. GV SDS was calculated using SAS algorithm. Growth velocity during the study was calculated using the two height measures as: GV = (Height at baseline - Height at screening)*365/delay between two height measures. | Baseline and month 6 | 
| Difference Between Bone Age and Chronological Age | Bone age was defined according to Greulich and Pyle method. Chronological age was calculated using the date of birth. | Month 0 and 6 | 
| Uterine Length |  | Month 0, 3 and 6 | 
| Triptorelin Plasma Levels |  | Month 1, 2, 3, 4, 5 and 6 |