Clinical trial NCT00635817: A Study of Leuprolide 11.25 mg and 30 mg Administered Every 3 Months to Treat Central Precocious Puberty
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Puberty, Precocious
Keywords: CPP
central precocious puberty
pediatrics
suppression of luteinizing hormone
Lupron
leuprolide acetate
depot formulation
GnRHa
GnRH agonist
GnRH analog
luteinizing hormone
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2008-03-14
Enrollment: 84
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Suppression of Peak Stimulated Luteinizing Hormone (<4 mIU/mL) From Month 2 Through Month 6
timeFrame: Month 2 through 6
Secondary outcomes:
measure: Percentage of Participants With Suppression of Basal Estradiol <20 pg/mL by Visit
timeFrame: Month 1, 2, 3 and 6
measure: Percentage of Participants With Suppression of Testosterone in <30 ng/dL by Visit
timeFrame: Month 1, 2, 3 and 6
measure: Peak-stimulated Luteinizing Hormone Concentration by Visit
timeFrame: Baseline, Month 1, 2, 3 and 6
measure: Percentage of Participants With Suppression of the Physical Signs of Puberty (Breast Development) at Month 6
timeFrame: Month 6
measure: Percentage of Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) at Month 6
timeFrame: Month 6
measure: Change From Baseline in Incremental Growth Rate (cm/Year) at Month 6
timeFrame: Baseline and Month 6
measure: Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age at Month 6
timeFrame: Baseline to Month 6
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Site Reference ID/Investigator# 8765
state: Alabama
city: Long Beach
country: United States
facility: Site Reference ID/Investigator# 11522
state: California
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator# 8756
state: California
city: San Diego
country: United States
facility: Site Reference ID/Investigator# 8755
state: California
city: San Diego
country: United States
facility: Site Reference ID/Investigator# 8761
state: California
city: Stanford
country: United States
facility: Site Reference ID/Investigator# 8772
state: California
city: Greenwood Village
country: United States
facility: Site Reference ID/Investigator# 8749
state: Colorado
city: Gainesville
country: United States
facility: Site Reference ID/Investigator# 8771
state: Florida
city: Jacksonville
country: United States
facility: Site Reference ID/Investigator# 8764
state: Florida
city: Pensacola
country: United States
facility: Site Reference ID/Investigator# 17621
state: Florida
city: Indianapolis
country: United States
facility: Site Reference ID/Investigator# 8752
state: Indiana
city: Shreveport
country: United States
facility: Site Reference ID/Investigator# 8766
state: Louisiana
city: Minneapolis
country: United States
facility: Site Reference ID/Investigator# 8768
state: Minnesota
city: St. Paul
country: United States
facility: Site Reference ID/Investigator# 17341
state: Minnesota
city: Kansas City
country: United States
facility: Site Reference ID/Investigator# 8759
state: Missouri
city: Oklahoma City
country: United States
facility: Site Reference ID/Investigator# 8750
state: Oklahoma
city: Tulsa
country: United States
facility: Site Reference ID/Investigator# 8760
state: Oklahoma
city: Hershey
country: United States
facility: Site Reference ID/Investigator# 8763
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Site Reference ID/Investigator# 8754
state: Utah
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 8762
state: Washington
city: Seattle
country: United States
facility: Site Reference ID/Investigator# 8753
state: Washington
city: Bayamon
country: Puerto Rico
facility: Site Reference ID/Investigator# 17922
city: Ponce
country: Puerto Rico
facility: Site Reference ID/Investigator# 17923
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 18242
city: San Juan
country: Puerto Rico
facility: Site Reference ID/Investigator# 19661
Study officials:
affiliation: Abbott
name: Peter Bacher, MD,
role: STUDY_DIRECTOR
References:
citation: Lee PA, Klein K, Mauras N, Neely EK, Bloch CA, Larsen L, Mattia-Goldberg C, Chwalisz K. Efficacy and safety of leuprolide acetate 3-month depot 11.25 milligrams or 30 milligrams for the treatment of central precocious puberty. J Clin Endocrinol Metab. 2012 May;97(5):1572-80. doi: 10.1210/jc.2011-2704. Epub 2012 Feb 16.