Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty
- Registration Number
- NCT02452931
- Lead Sponsor
- Tolmar Inc.
- Brief Summary
This study determines the effectiveness of leuprolide acetate 45 mg for injectable suspension for treatment of children with Central Precocious Puberty.
- Detailed Description
Leuprolide acetate is a GnRH agonist that inhibits pituitary gonadotropin secretion by binding to the GnRH receptors and blocking downstream hormone synthesis. The steady decrease in hormone synthesis (LH and FSH) leads to a suppression of testicular and ovarian steroidogenesis. In children with CPP, this steady decrease in hormone synthesis disrupts the progression of puberty.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- Females age 2 to 8 years (inclusive) or males age 2 to 9 years (inclusive)
- Confirmed diagnosis of CPP within 12 months of Baseline Visit (Day 0) but have not received prior GnRH agonist treatment for CPP
- Pubertal-type LH response following an abbreviated GnRHa stimulation test before treatment initiation
- Clinical evidence of puberty, defined as Tanner stage ≥ 2 for breast development in females or testicular volume ≥ 4 mL in males
- Difference between bone age (Greulich and Pyle method) and chronological age ≥ 1 year
- Gonadotropin-independent (peripheral) precocious puberty
- Prior or current GnRH treatment for CPP
- Prior or current therapy with medroxyprogesterone acetate, growth hormone or insulin-like growth factor-1 (IGF-1)
- Diagnosis of short stature (ie, 2.25 standard deviations (SD) below the mean height for age)
- Known history of seizures, epilepsy, and/or central nervous system disorders that may be associated with seizures or convulsions
- Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Assigned Intervention Leuprolide Acetate 45 mg Leuprolide acetate 45 mg will be administered as a subcutaneous injection at 6-month intervals for the 12 month study period.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months. 6 months Luteinizing Hormone (LH) suppression is defined as peak-stimulated LH \<4 IU/L. Peak stimulated LH refers to the maximum LH concentration measured 30 minutes after a gonadotropin-releasing hormone agonst (GnRHa) stimulation test.
- Secondary Outcome Measures
Name Time Method Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels. Week 12, Week 24, Week 36, and Week 48 Percentage of subjects with suppressed serum LH concentrations(\<4 IU/L) 30 minutes post GnRHa stimulation test at all assessed timepoints.
Changes in Height Velocity (Growth Rate) Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48 Changes in height velocity (growth rate) at all study timepoints after Screening to end of study. Growth velocity is defined for each visit as change from baseline / \[(number of weeks since baseline)/52\]. Week 48: Change from Week 24 growth velocity is defined as change from week 24 to week 48 / \[(number of weeks since week 24)/52\].
Bone Age Ratio to Chronological Age at Time of Measurement Week 24 and Week 48 Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.
Tanner Scores: Boys - Development of External Genitalia Baseline, Week 12, Week 24, Week 36, and Week 48 Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Tanner Scores: Boys and Girls - Pubic Hair Baseline, Week 12, Week 24, Week 36, and Week 48 Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline) Week 12, Week 24, Week 36, and Week 48 Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Tanner Scores: Girls - Breast Development Baseline, Week 12, Week 24, Week 36, and Week 48 Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Tanner Scores: Boys - Development of External Genitalia (Change From Baseline) Week 12, Week 24, Week 36, and Week 48 Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Tanner Scores: Girls - Breast Development (Change From Baseline) Week 12, Week 24, Week 36, and Week 48 Sexual development (physical signs) in puberty were assessed by Tanner staging, a system developed by Marshall and Tanner to categorize pubertal maturation. Tanner stages are commonly used to categorize pubertal maturation in terms of sequence, timing and tempo. Tanner Stages: the minimum is Stage 1 = pre-pubertal physical characteristics and the maximum is Stage 5 = fully matured (adult) physical characteristics.
Percent Change From Baseline in Height Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48 The percent change from baseline in height at each available post-baseline measurement. Percent change is defined as (((change from Baseline)/(Baseline)) x 100).
Trial Locations
- Locations (20)
University of Oklahoma College of Medicine
🇺🇸Tulsa, Oklahoma, United States
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
The Liggins Institute, University of Auckland
🇳🇿Auckland, New Zealand
CHU de Quebec-Universite Laval
🇨🇦Quebec, Canada
MultiCare Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States
University of Calgary, Alberta Children's Hospital
🇨🇦Calgary, Alberta, Canada
Joe DiMaggio Children's Hospital
🇺🇸Hollywood, Florida, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Pontificia Universidad Catolica de Chile
🇨🇱Santiago, Metropolitana, Chile
Hospital Unversitario "Dr. Jose Eleuterio Gonzalez"
🇲🇽Monterrey, Nuevo Leon, Mexico
Instituto de Investigaciones Aplicadas a la Neurociencia, A.C.
🇲🇽Durango, Mexico
Hospital de Ninos
🇦🇷Buenos Aires, Argentina
Instituto de Investigaciones Materno Infantil (IDIMI)
🇨🇱Santiago, Metropolitana, Chile
Hospital Regional de Antofagasta Leonardo Guzman
🇨🇱Antofagasta, Second Region, Chile
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of California, San Diego
🇺🇸San Diego, California, United States
Nemours Children's Hospital
🇺🇸Orlando, Florida, United States
Riley Hospital for Children at Indiana University Health
🇺🇸Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center, Endocrine
🇺🇸Cincinnati, Ohio, United States
Seattle Children's
🇺🇸Seattle, Washington, United States