Official Title: “Study of Lupron Depot In The Treatment of Central Precocious Puberty”

The purpose of this study is to determine if leuprolide acetate is safe and effective in treating children with Central Precocious Puberty, and to assess long term effects of leuprolide acetate treatment after therapy is discontinued.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2001

This study will use hormonal and physical measurements to determine if leuprolide acetate is safe and effective for treating children with central precocious puberty. The dose of leuprolide acetate for depot suspension will start at 300 mcg/kg (minimum 7.5 mg), given in the muscle every 28 days, with incremental adjustments of 3.75 mg (minimum 7.5 mg and maximum15 mg) if needed based on clinical and laboratory measurements. Approximately 10 study sites will participate in a total of 50 or more subjects. This study includes a Prestudy Period and once enrolled, patients will be followed at least every 12 weeks for the first year and then, every 6 months thereafter until the drug is discontinued (until the NDA is approved or the IND is withdrawn, or until treatment is discontinued at the discretion of the physician or parent.) At the treatment visits, gonadotropins/sex steroid levels, safety labs, physical exam, bone age by radiograph, height, weight, and Tanner stage will be assessed.In addition, this protocol will capture long-term outcome data on reproductive function, final height and incidence of ovarian cysts as these children reach adulthood.Following discontinuation of therapy (puberty), patients will be assessed for height, weight, Tanner staging, bone age, gonadotropin / sex steroid levels, ultrasound, menstrual history for girls and urine sample for presence of sperm for boys at specified visits for 5 years until puberty is reached, then annually until 21 years of age for height and reproductive potential. To collect final information on adult height, reproductive potential and ovarian cysts, patients will be contacted and asked to return for a final clinic visit and complete a questionnaire, have a final height and weight measurement, and females will undergo an abdominal ultrasound to assess ovarian cysts. Following this data collection, the study will be concluded.

Intervention(s) in this Clinical Trial

• Drug: Leuprolide acetate
  • Depot suspension administered monthly by intramuscular injection starting at 300 mcg/kg with adjustments of 3.75 mg upward, if necessary at subsequent clinic visits based on physical and laboratory parameters. Dosing continued until NDA was approved, or until subject no longer required leuprolide acetate to treat central precocious puberty.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1

Primary Measures

• The clinical sexual characteristics evaluated using Tanner staging (pubic hair and genital development in males, pubic hair and breast development in females).
  • Time Frame: Weeks 4, 8, 12, 24, 36, 48, then every 6 months until end of treatment, and end of treatment day.
    Safety Issue?: No

Secondary Measures

• Hormone laboratory test results (LH suppression).
  • Time Frame: Weeks 4, 8, 12, 24, 36, 48, and then every 6 months until end of treatment, and end of treatment day.
    Safety Issue?: No
• Ratio of change in bone age to the change in chronological age.
  • Time Frame: Weeks 24 and 48 then every 12 months until end of treatment and end of treatment day.
    Safety Issue?: No
• Predicted mature height.
  • Time Frame: Weeks 24 and 48, then every 12 months until end of treatment, and end of treatment day.
    Safety Issue?: No

Inclusion Criteria:

• Clinical diagnosis of isosexual central precocious puberty with onset of Tanner scores of Stage II for breast or pubic hair earlier than age 8.0 years in girls or Stage II for pubic hair or genitalia earlier than 9.0 years in boys.
• Confirmation of diagnosis by a pubertal response to a GnRH stimulation test (LH > 10
• U/L at baseline).
• Chronological age less than 9.0 years in girls or less than 10.0 years in boys at time of first dosing.
• Bone age advanced at least one year beyond the chronological age at entry into the study.
• The condition may be idiopathic or secondary to another lesion. If secondary, therapy of the primary condition will have been undertaken and stabilized.
• No evidence of abnormal pituitary, adrenal, thyroid and gonadal function except for premature secretion of gonadotropins.

Exclusion Criteria:

• Irradiation to the central nervous system.
• Prior therapy with medroxyprogesterone acetate and/or with any GnRH analog (including prior treatment with daily subcutaneous and depot formulations of leuprolide acetate).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 10 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.675 North Field Drive Lake Forest, IL 60045  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00660010

Study ID Number: M90-516

ClinicalTrials.gov Identifier: NCT00660010

Health Authority: United States: Food and Drug Administration

(For the Lupron PEDs Package Insert, refer to this link:)

(For FDA Safety Alerts and Recalls, refer to this link:)