A Study of Leuprolide 11.25 mg and 30 mg Administered Every 3 Months to Treat Central Precocious Puberty
Condition: Puberty, Precocious
MeSH terms: Puberty, Precocious
Intervention: Leuprolide acetate 11.25 mg; Leuprolide acetate 30 mg
Intervention description: Two intramuscular injections of leuprolide acetate for depot suspension 11.25 mg administered 3 mo apart.; Two intramuscular injections of leuprolide acetate for depot suspension 30 mg administered 3 mo apart.
Intervention MeSH terms: Leuprolide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 84.0
Sex: All
Minimum age: 2 Years
Maximum age: 11 Years
Healthy volunteers: No
Keywords: CPP; central precocious puberty; pediatrics; suppression of luteinizing hormone; Lupron; leuprolide acetate; depot formulation; GnRHa; GnRH agonist; GnRH analog; luteinizing hormone

Summary:

      The purpose of this study is to determine if 11.25 and 30 mg formulations of leuprolide are
      effective in treating children with Central Precocious Puberty (CPP).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has a clinical diagnosis of CPP.

          -  Eligible to receive at least 6 mo of therapy to treat CPP after study entry.

          -  Bone age advanced at least 1 year beyond the chronological age at time of diagnosis or
             first treatment.

          -  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 who have not had previous treatment:

          -  Girls 2-8 years inclusive or Boys 2-9 years inclusive at Day 1.

          -  Has pretreatment pubertal response to leuprolide acetate stimulation (luteinizing
             hormone ≥8 mIU/mL) at Screening.

          -  Breast pubertal staging of at least 2 in girls; testicular volume of at least 4 cc or
             testicular length greater than 2.5 cm in boys at Screening.

        Additional criteria for subjects previously treated:

          -  Girls 2-10 years inclusive or boys 2-11 years inclusive at Day 1.

          -  Must have been on standard gonadotropin releasing hormone analog therapy for at least
             the 6 mo prior to Day 1.

          -  Has documented maintenance of luteinizing hormone suppression as evidenced by peak
             stimulated level <4 mIU/mL at Screening.

        Exclusion Criteria:

          -  Incomplete precocious puberty (premature thelarche, premature adrenarche).

          -  Peripheral precocious puberty: gonadal or adrenal tumors, congenital adrenal
             hyperplasia, testotoxicosis in boys, human chorionic gonadotropin secreting tumor or
             McCune-Albright syndrome in girls.

          -  Evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid and gonadal
             function other than premature secretion of gonadotropins not adequately controlled.

          -  Unstable intracranial tumors (unresponsive to treatment/expanding) except hamartoma.

          -  Previous treatment with GnRHa therapy requiring leuprolide acetate for depot
             suspension >15 mg monthly.

          -  Bone age >13 years for girls and >14 years for boys.

          -  Any other condition interfering with growth, ie, skeletal dysplasia, cerebral palsy.

          -  Chronic illness requiring treatment that may interfere with growth, ie, chronic
             steroid use, renal failure, moderate to severe scoliosis.

          -  Diagnosis of short stature, ie more than 2.25 standard deviations below the mean
             height for age (growth chart measurement).

          -  Prior or current therapy with medroxyprogesterone acetate or growth hormone.

          -  Has an abnormal laboratory value suggesting a clinically significant underlying
             disease .

          -  Creatinine >1.5 mg/dL, alanine aminotransferase and/or aspartate aminotransferase >2.0
             x upper limit of normal, or total bilirubin >2.0 mg/dL with aspartate
             aminotransferase/alanine aminotransferase elevated above normal limits.

          -  Positive pregnancy test.

          -  Known hypersensitivity to study medication or its excipients.

          -  Participation in another drug research within 3 mo of enrollment into this study.

          -  Prior or current therapy with insulin-like growth factor-1.

          -  Use of an estrogen preparation within 2 mo prior to Day 1.