Central Precocious Puberty MedDRA version: 17.1 Level: LLT Classification code 10073186 Term: Central precocious puberty System Organ Class: 100000004860
Conditions
Interventions
Trade Name: trade name depends on the source of the product
Product Name: Leuprolide acetate depot
Pharmaceutical Form: Suspension for injection in pre-filled syringe
INN or Proposed INN: LEUPRORELIN
Sponsors
Abbvie previously known as Abbott
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The informed consent form, assent form and any privacy statement (e.g., HIPAA) must be approved by a local or central Institutional Review Board (IRB) as required by State and local regulations. Prior to performing any trial-related procedures, each subject's parent must review, understand, and sign an informed consent form. When determined to be appropriate (as specified either by the IRB and/or State and local regulations), each subject must also sign the assent form after having had an opportunity to review the form and have its contents explained and questions answered. 2. Subject has a clinical diagnosis of CPP. 3. Eligible to receive at least 6 months of therapy to treat CPP after study entry. 4. Chronological age at onset of pubertal symptoms less than 8 years old in girls and less than 9 years old in boys at Day 1. 5. Bone age advanced at least 1 year beyond the chronological age at time of diagnosis or first GnRHa therapy. 6. In general good health with no uncontrolled, clinically significant disease which would interfere with bone maturation or mask the objectives of this protocol as assessed by the investigator. Additional criteria for subjects naïve to GnRHa treatment: 7. Girls 2-8 years inclusive or Boys 2-9 years inclusive at Day 1 8. Pretreatment pubertal response to leuprolide acetate stimulation (LH = 8 mIU/mL) at Screening. 9. Breast pubertal staging of at least II in Girls; testicular volume of at least 4cc or testicular length greater than 2.5 cm in Boys at Screening. Additional criteria for subjects previously treated with GnRHa: 10. Girls 2-10 years inclusive or Boys 2-11 years inclusive at Day 1. 11. Must have been on standard GnRHa therapy for at least the 6 months prior to Day 1. to the end of their previous GnRHa treatment cycle. 12. Should have documented maintenance of LH suppression as evidenced by peak stimulated LH =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Incomplete precocious puberty (premature thelarche, premature adrenarche). 2. Peripheral precocious puberty: gonadal or adrenal tumors, congenital adrenal hyperplasia, testotoxicosis in boys, hCG secreting tumor or McCune-Albright syndrome in girls. 3. Evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid and gonadal function other than premature secretion of gonadotropins not adequately controlled. 4. Unstable intracranial tumors (unresponsive to treatment/expanding) except hamartoma. 5. Previous treatment with GnRHa therapy requiring leuprolide acetate for depot suspension > 15 mg monthly. 6. Bone age > 13 years for girls and > 14 years for boys. 7. Any other condition interfering with growth, i.e., skeletal dysplasia, cerebral palsy. 8. Chronic illness requiring treatment that may interfere with growth, i.e., chronic steroid use, renal failure, moderate to severe scoliosis. 9. Diagnosis of short stature, i.e., more than 2.25 SD below the mean height for age (growth chart measurement). 10. Prior or current therapy with medroxyprogesterone acetate. 11. Prior or current therapy with growth hormone. 12. Subject has an abnormal laboratory value that suggest a clinically significant underlying disease or condition that may prevent the subject from entering the study or subject with the following laboratory abnormalities: Creatinine > 1.5 mg/dL, ALT and/or AST > 2.0 × ULN, or total bilirubin > 2.0 mg/dL with AST/ALT elevated above normal limits. 13. Subject has a positive pregnancy test. 14. Any concomitant medical condition that, in the opinion of the investigator, may expose a subject to an unacceptable level of safety risk or that affects subject compliance. 15. Known hypersensitivity to study medication or its excipients. 16. Subject is a family member of the investigator, sub investigator, or study coordinator. Family member is defined to include either a child (including step or foster child), niece, nephew, sibling or cousin. 17. Participation in another drug research within 3 months of randomization into this study. 18. Prior or current therapy with IGF-1. 19. Use of an estrogen preparation within 2 months prior to Day 1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy and safety of the 11.25 mg and 30 mg formulations of leuprolide acetate for the treatment of central precocious puberty (CPP) in children who either are naïve to previous treatment with gonadotropin-releasing hormone analog (GnRHa) or who have previously been treated with GnRHa for at least the prior 6 months.;Secondary Objective: To evaluate the pharmacokinetic (PK) profile of leuprolide following intramuscular (IM) administration of the 11.25 and 30 mg depot formulations in a subset of subjects with CPP.;Primary end point(s): Suppression of LH from Month 2 through Month 6 as determined by peak stimulated LH < 4 mIU/mL at Months 2, 3 and 6.;Timepoint(s) of evaluation of this end point: months 2,3 and 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Suppression of sex steroids (E2 < 20 pg/mL in girls and T < 30 ng/dL in boys) measured at Months 1, 2, 3 and 6. ? Peak stimulated LH concentrations at Months 1, 2, 3 and 6. ? Suppression of the physical signs of puberty at Month 6 (subjects entering the study with Pubertal staging 5 will be excluded from this analysis), defined as: ? Regression or no progression of breast development according to Pubertal staging (in girls). ? Regression or no progression in testicular volume and genital staging according to Pubertal staging (boys). ? Change from baseline in growth rate after 6-months of treatment within each of the subgroups of subjects naïve to GnRHa treatment and previously treated. ? The ratio of change from baseline in bone age/change from baseline in chronological age after 6 months of treatment within each of the subgroups of subjects naïve to GnRHa treatment and previously treated.;Timepoint(s) of evaluation of this end point: months 1,2,3 and 6 | — |
Countries
Puerto Rico, United States
Contacts
Public ContactEU Clinical Trials Helpdesk
AbbVie Ltd.
Outcome results
None listed