A Study of Leuprolide 11.25 mg and 30 mg Administered Every 3 Months to Treat Central Precocious Puberty

A Phase 3, Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy and Safety of Leuprolide Acetate 11.25 and 30 mg Formulations in Children With Central Precocious Puberty

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).

Study Design:

A total of 80 children with confirmed CPP were planned to be enrolled and randomized in a 1:1 ratio to receive 2 injections of either leuprolide acetate 11.25 mg or 30 mg depot formulation, each injection administered 3 mo apart (6 mo of treatment):

This study includes a 4-week Screening Period, two 3-mo treatment cycles, and a posttreatment follow-up period (12 weeks following the Mo 6 visit). Study visits will occur at Screening, Day 1, Week 2 (only for subjects participating in the pharmacokinetic subset), Mo 1, 2, 3, Mo 6/Early Termination, and 12 weeks later, for the Posttreatment Follow-up Visit.

This study was conducted at 18 sites in the United States and 4 sites in Puerto Rico.

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.