Efficacy and Safety Study of Triptorelin 3-Month Formulation in Chinese Children With Central Precocious Puberty.

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to observe whether the Triptorelin pamoate 15mg (3-month formulation) effectiveness in Chinese population of CPP children has the same or similar trend with that in overseas CPP population. 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 of triptorelin.

Detailed Description
-----------------
For patients enter extension phase, two additional Triptorelin injections will be given at month 6 and month 9 visits.

Official Title
-----------------
An Open-label, Multicentre, Single Arm Study to Assess the Efficacy and Safety of Triptorelin 3-month Formulation in Chinese Children With Central Precocious Puberty

Conditions
-----------------
Central Precocious Puberty

Intervention / Treatment
-----------------
* Drug: Triptorelin pamoate 15mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Onset of development of secondary 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: Stage II Pubertal response of LH to GnRH stimulation test (stimulated peak LH ≥5 IU/L) Difference between bone age (BA) (according to Greulich and Pyle method) and chronological age (CA) >1 year Girls with Tanner staging ≥2 for breast development and enlarged uterine length and several follicles with diameter >4 mm in the ovary at Screening visit; boys who have testicular volume ≥4 mL at Screening visit Age < 9 years old for girls and < 10 years old for boys at initiation of triptorelin treatment Weight at least 20 kg Subjects will qualify for the extension phase if they sign the corresponding specific consent form, are still benefiting from treatment at the end the primary study and have not experienced any unacceptable safety issues. Exclusion 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. Participants with hamartomas not requiring surgery are eligible Evidence of renal (creatinine >1.5 x upper limit of normal (ULN)) or hepatic impairment (bilirubin >1.5 x ULN or alanine aminotransferase (ALT)/aspartate transaminase (AST) >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 topical steroids, renal failure, diabetes, moderate to severe scoliosis) Prior or current therapy with a GnRH agonist (GnRHa), medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1) Diagnosis of short stature, i.e. >2.25 standard deviation (SD) below the mean height for age Major medical or psychiatric illness that could interfere with study visits Known hypersensitivity to any of the test materials or related compounds Use of anticoagulants (heparin and coumarin derivatives) within the 2 weeks prior to the Screening visit.

Ages Eligible for Study
-----------------
Maximum Age: 10 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 15mg for injection<br>Triptorelin will be injected at day 1 and month 3. If participants are willing to enter extension phase, two additional Triptorelin injections will be given at month 6 and month 9. | Drug: Triptorelin pamoate 15mg<br>* Intramuscular injection (IM)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of children with Luteinising Hormone (LH) suppression defined as stimulated peak LH ≤3 IU/L after Gonadotropin-releasing Hormone (GnRH) stimulation |  | 3 months after first injection of study drug (for main study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Basal Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH) serum levels |  | Baseline, Month 3 and Month 6 (End of Study of main study), for the extension phase study: month 9 and month 12 | 
| Peak LH after GnRH stimulation test |  | Baseline, Month 3 and Month 6 (End of Study of main study), for the extension phase study: month 12] | 
| Peak FSH levels after GnRH stimulation test |  | Baseline, Month 3 and Month 6 (End of Study of main study), for the extension phase study: month 12. | 
| Oestradiol or testocterone serum concentration |  | Baseline, Month 3 and Month 6 (End of Study of main study), for the extension phase study month 9 and month 12. | 
| Pubertal stage (Tanner Method) |  | Baseline and Month 6 (End of Study of main study) and month 12 for the extension phase study. | 
| Auxological parameters (height, growth velocity, weight, BMI) |  | Baseline, Month 3 and Month 6 (End of Study of main study), for the extension phase study: month 9 and 12. | 
| Bone Age |  | Baseline and Month 6 (End of Study of main study) and month 12 for the extension phase study. | 
| Gonad development (Uterine length or testis volume) |  | Baseline and Month 6 (End of Study of main study) and month 12 for the extension phase study. | 
| Proportion of children with LH suppression defined as stimulated peak LH ≤3 IU/L after GnRH stimulation |  | Month 6 of main study and at month 12 for the extension phase study. | 
| Proportion of children with pre-pubertal levels of sex steroids (defined as oestradiol ≤20 pg/mL in girls and testosterone ≤0.3 ng/mL in boys) |  | Month 3 and Month 6 for the main study and for the extension phase study: month 9 and month 12. | 
| Proportion of children with stabilised pubertal stage compared to baseline stage using the Tanner method |  | Month 6 for the main study and month 12 for the extension phase study. |