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

Puberty, Precocious Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00635817
• Other study ID #: L-CP07-167
• Status: Completed
• Phase: Phase 3
• First received: March 7, 2008
• Last updated: October 25, 2011
• Start date: June 2008
• Est. completion date: June 2010

Study information

• Verified date: October 2011
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: June 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 11 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Puberty, Precocious

Intervention

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

Locations

Country	Name	City	State
Puerto Rico	Site Reference ID/Investigator# 17922	Bayamon
Puerto Rico	Site Reference ID/Investigator# 17923	Ponce
Puerto Rico	Site Reference ID/Investigator# 18242	San Juan
Puerto Rico	Site Reference ID/Investigator# 19661	San Juan
United States	Site Reference ID/Investigator# 8765	Birmingham	Alabama
United States	Site Reference ID/Investigator# 8771	Gainesville	Florida
United States	Site Reference ID/Investigator# 8749	Greenwood Village	Colorado
United States	Site Reference ID/Investigator# 8763	Hershey	Pennsylvania
United States	Site Reference ID/Investigator# 8752	Indianapolis	Indiana
United States	Site Reference ID/Investigator# 8764	Jacksonville	Florida
United States	Site Reference ID/Investigator# 8759	Kansas City	Missouri
United States	Site Reference ID/Investigator# 11522	Long Beach	California
United States	Site Reference ID/Investigator# 8756	Los Angeles	California
United States	Site Reference ID/Investigator# 8768	Minneapolis	Minnesota
United States	Site Reference ID/Investigator# 8750	Oklahoma City	Oklahoma
United States	Site Reference ID/Investigator# 17621	Pensacola	Florida
United States	Site Reference ID/Investigator# 8754	Salt Lake City	Utah
United States	Site Reference ID/Investigator# 8755	San Diego	California
United States	Site Reference ID/Investigator# 8761	San Diego	California
United States	Site Reference ID/Investigator# 8753	Seattle	Washington
United States	Site Reference ID/Investigator# 8762	Seattle	Washington
United States	Site Reference ID/Investigator# 8766	Shreveport	Louisiana
United States	Site Reference ID/Investigator# 17341	St. Paul	Minnesota
United States	Site Reference ID/Investigator# 8772	Stanford	California
United States	Site Reference ID/Investigator# 8760	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Suppression of Peak Stimulated Luteinizing Hormone (<4 mIU/mL) From Month 2 Through Month 6	Percentage of participants with suppression of peak stimulated luteinizing hormone that was measured after a gonadotropin-releasing hormone agonist (GnRHa) stimulation test at Month (Mo) 2, 3, and 6. The analysis was performed according to a life table method. Subjects who withdrew without peak-stimulated luteinizing hormone >= 4 mIU/mL were censored at their last measurement of peak-stimulated luteinizing hormone.	Month 2 through 6	No
Secondary	Percentage of Participants With Suppression of Basal Estradiol <20 pg/mL by Visit	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.	Month 1, 2, 3 and 6	No
Secondary	Percentage of Participants With Suppression of Testosterone in <30 ng/dL by Visit	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.	Month 1, 2, 3 and 6	No
Secondary	Peak-stimulated Luteinizing Hormone Concentration by Visit	Observed data were used with no imputation for missing data.	Baseline, Month 1, 2, 3 and 6	No
Secondary	Percentage of Participants With Suppression of the Physical Signs of Puberty (Breast Development) at 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.	Month 6	No
Secondary	Percentage of Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) at 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.	Month 6	No
Secondary	Change From Baseline in Incremental Growth Rate (cm/Year) at 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.	Baseline and Month 6	No
Secondary	Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age at 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.	Baseline to Month 6	No