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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 P

Brief 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).

Detailed Summary:

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.

Current Primary Outcome: Percentage of Participants With Suppression of Peak Stimulated Luteinizing Hormone (<4 mIU/mL) From Month 2 Through Month 6 [ Time Frame: Month 2 through 6 ]

Original Primary Outcome: Measure #1: 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. ]

Current Secondary Outcome:

• Percentage of Participants With Suppression of Basal Estradiol <20 pg/mL by Visit [ Time Frame: Month 1, 2, 3 and 6 ]
  Percentage of participants with suppression of estradiol, out of the number of girls with at least 1 estradiol measurement at each visit (n/N%). Only girls are analyzed in this outcome measure. Observed data were used with no imputation for missing data.
• Percentage of Participants With Suppression of Testosterone in <30 ng/dL by Visit [ Time Frame: Month 1, 2, 3 and 6 ]
  Percentage of participants with suppression of testosterone, out of the number of boys with at least 1 testosterone measurement at each visit (n/N%). Only boys are analyzed in this outcome measure. Observed data were used with no imputation for missing data.
• Peak-stimulated Luteinizing Hormone Concentration by Visit [ Time Frame: Baseline, Month 1, 2, 3 and 6 ]
  Observed data were used with no imputation for missing data.
• Percentage of Participants With Suppression of the Physical Signs of Puberty (Breast Development) at Month 6 [ Time Frame: Month 6 ]
  Percentage of participants with suppression of breast development, out of the number of girls with pubertal staging of breast development (n/N%). Only girls are analyzed in this outcome measure. Breast development was rated from Stage 1 (early development) through Stage 5 (full development) according to a Tanner Staging pictogram. Girls entering the study with fully developed breasts (Stage 5) were excluded from this analysis. Observed data were used with no imputation for missing data.
• Percentage of Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) at Month 6 [ Time Frame: Month 6 ]
  Percentage of participants with suppression of genital development and testicular volume, out of the number of boys with pubertal staging of genital development or testicular volume (n/N%). Only boys are analyzed in this outcome measure. External genital development (testes and penis) was rated from Stage 1 (early development) through Stage 5 (full development) according to a Tanner Staging pictogram. Boys entering the study with fully developed genitals (Stage 5) were excluded from this analysis. Observed data were used with no imputation for missing data.
• Change From Baseline in Incremental Growth Rate (cm/Year) at Month 6 [ Time Frame: Baseline and Month 6 ]
  The growth rate at baseline was the growth rate during the last year before the start of treatment and was calculated with the measurement closest to Day -336 (before Day -30) and the measurement up to Day 1. Growth rate at Month 6 was defined as the ratio of the change in height from Day 1 to the change in chronological age, with an approximate 6-month interval between the 2 height measurements. Observed data were used with no imputation for missing data.
• Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age at Month 6 [ Time Frame: Baseline to Month 6 ]
  The ratio at Month 6 was calculated as (bone age at Month 6 - bone age at baseline)/(chronological age at Month 6 - chronological age at baseline). Observed data were used with no imputation for missing data. Baseline bone-age radiograph was performed at or within 3 months of the Screening Visit.

Original Secondary Outcome:

• Suppression of sex steroids (E2 <20 pg/mL in girls and T <30 ng/dL in boys). [ Time Frame: Months 1, 2, 3 and 6. ]
• Peak stimulated luteinizing hormone concentrations. [ Time Frame: 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 in girls as regression or no progression of breast development according to Pubertal staging and in [ Time Frame: Month 6 ]
• 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 ]
• 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. ]

Dates:
Date Received: March 7, 2008
Date Started: June 2008
Date Completion:
Last Updated: October 25, 2011
Last Verified: October 2011