Official Title: “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 new formulations (11.25 and 30 mg) of leuprolide are effective in treating children with Central Precocious Puberty.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2010

Study Design:

Approximately 80 children with confirmed Central Precocious Puberty will be randomized in a 1:1 ratio to receive a total of two (2) injections of either leuprolide acetate 11.25 mg or 30 mg depot formulation, each injection administered 3 months apart (6 months of treatment):

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

Intervention(s) in this Clinical Trial

• Drug: Leuprolide acetate 11.25 mg
  • Two intramuscular injections of leuprolide acetate for depot suspension 11.25 mg administered 3 months apart.
• Drug: Leuprolide acetate 30 mg
  • Two intramuscular injections of leuprolide acetate for depot suspension 30 mg administered 3 months apart.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2

Primary Measures

• Suppression of luteinizing hormone (<4 mIU/mL) from month 2 through month 6 as determined by peak stimulated luteinizing hormone.
  • Time Frame: Months 2, 3 and 6.
    Safety Issue?: No

Secondary Measures

• Suppression of sex steroids (estradiol <20 pg/mL in girls and testosterone <30 ng/dL in boys).
  • Time Frame: Months 1, 2, 3 and 6.
    Safety Issue?: No
• Peak stimulated luteinizing hormone concentrations.
  • Time Frame: Months 1, 2, 3 and 6.
    Safety Issue?: No
• Suppression of the physical signs of puberty at Month 6 (subjects entering the study with Pubertal staging 5 will be excluded from this analysis).
  • Time Frame: Month 6
    Safety Issue?: No
• Change from baseline in growth rate after 6 months of treatment within each of the subgroups of not previously treated and previously treated children.
  • Time Frame: Month 6
    Safety Issue?: No
• 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 not previously treated and previously treated children.
  • Time Frame: Month 6.
    Safety Issue?: No

Inclusion Criteria:

• Subject has a clinical diagnosis of Central Precocious Puberty.
• Eligible to receive at least 6 months of therapy to treat Central Precocious Puberty 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 (LH ≥8 mIU/mL) at
• Screening.
• 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:

• 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 months 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 >15mg 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 SD below the mean height for age (growth chart measurement).
• Prior or current therapy with medroxyprogesterone acetate or growth hormone.
• Has an abnormal laboratory values suggesting a clinically significant underlying disease .
• Creatinine >1.5 mg/dL, ALT and/or AST >2.0 x ULN, or total bilirubin >2.0 mg/dL with AST/ALT elevated above normal limits.
• Positive pregnancy test.
• Known hypersensitivity to study medication or its excipients.
• Participation in another drug research within 3 months of enrollment into this study.
• Prior or current therapy with IGF-1.
• Use of an estrogen preparation within 2 months prior to Day 1.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 2 Years

Maximum Age for this Clinical Trial: 11 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: TAP Pharmaceutical Products Inc.

Overall Clinical Trial Officials and Contacts

Medical Director Study Chair TAP Pharmaceutical Products Inc.  

Overall Contact: TAP ClinicalTrials.gov Call Center 800-778-2860 medical.affairs@tap.com

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00635817

Study ID Number: L-CP07-167

ClinicalTrials.gov Identifier: NCT00635817

Health Authority: United States: Food and Drug Administration

For the Lupron PEDs Package Insert, refer to this link

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