Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty

Precocious Puberty, Central Clinical Trial

Official title:

An Open-label, Single Arm, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Leuprolide Acetate 45 mg for Injectable Suspension Controlled Release in Subjects With Central (Gonadotropin-Dependent) Precocious Puberty

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02452931
• Other study ID #: TOL2581A
• Status: Completed
• Phase: Phase 3
• Start date: August 31, 2015
• Est. completion date: September 5, 2018

Study information

• Verified date: May 2020
• Source: Tolmar Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study determines the effectiveness of leuprolide acetate 45 mg for injectable suspension for treatment of children with Central Precocious Puberty.

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.

Other known NCT identifiers

• NCT02811471

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: September 5, 2018
• Est. primary completion date: September 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 9 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Precocious Puberty, Central
• Puberty, Precocious

Intervention

Drug:
• Leuprolide Acetate 45 mg
Subcutaneous injection

Locations

Country	Name	City	State
Argentina	Hospital de Ninos	Buenos Aires
Canada	University of Calgary, Alberta Children's Hospital	Calgary	Alberta
Canada	McGill University Health Centre	Montreal	Quebec
Canada	CHU de Quebec-Universite Laval	Quebec
Chile	Hospital Regional de Antofagasta Leonardo Guzman	Antofagasta	Second Region
Chile	Instituto de Investigaciones Materno Infantil (IDIMI)	Santiago	Metropolitana
Chile	Pontificia Universidad Catolica de Chile	Santiago	Metropolitana
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia, A.C.	Durango
Mexico	Hospital Unversitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo Leon
New Zealand	The Liggins Institute, University of Auckland	Auckland
United States	Cincinnati Children's Hospital Medical Center, Endocrine	Cincinnati	Ohio
United States	Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Nemours Children's Hospital	Orlando	Florida
United States	University of California, San Diego	San Diego	California
United States	Seattle Children's	Seattle	Washington
United States	MultiCare Institute for Research and Innovation	Tacoma	Washington
United States	University of Oklahoma College of Medicine	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Tolmar Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  Mexico,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Height	Height at each available measurement point. Baseline is defined as the last non-missing height measurement collected prior to or on the date of first injection.	Screening, Baseline, Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Other	Bone Age	Bone Age at each available measurement point.	Baseline, Week 24, and Week 48
Other	Bone Age Progression	Bone age progression at each available post-baseline measurement point. Bone age progression is defined as (((change from baseline)/(baseline)) x 100), which is percent change from baseline.	Week 24 and Week 48
Other	Bone Age Ratio to Chronological Age at Time of Measurement (Percent Change From Baseline)	Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.	Week 24 and Week 48
Other	Bone Age Ratio to Chronological Age at Start of Study (Percent Change From Baseline)	Bone age advancement was evaluated relative to chronological age at each given measurement point. Percent change from baseline is: 100 x (the change from baseline value at the post-baseline visit / baseline value).	Week 24 and Week 48
Other	Bone Age Ratio to Chronological Age at Start of Study	Bone age advancement was evaluated relative to chronological age at each given measurement point. Bone Age Ratio to Chronological Age at Start of Study is bone age/age at first injection.	Baseline, Week 24, and Week 48
Other	GnRH Antagonist Evaluation	GnRH Antagonist Evaluation occurred for the two week period following each treatment and at each visit to assess flare symptoms. The percent of subjects who affirm (or whose parent/guardian affirms) each symptom domain in the global interview.	Week 2, Week 4, Week 12, Week 20, Week 24, Week 26, Week 36, Week 44, and Week 48
Other	Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels.	The percentage of subjects with FSH, estradiol and testosterone suppression to prepubertal levels (FSH < 2.5 mIU/mL, estradiol < 20 pg/mL and testosterone < 28.4 ng/dL) at each available time point.	Week 12, Week 24, Week 36, and Week 48
Other	Changes in the Ratio of LH/FSH	Changes in ratio of LH/FSH at each time point from Screening to End of Study	Screening (Pre&Post GnRHa Stim Test), Baseline (0,1,4,6 hours Post-Injection), Week 4, Week 12 (Pre&Post GnRHa Stim Test), Week 20, Week 24 (Pre&Post GnRHa Stim Test), Week 36 (Pre&Post GnRHa Stim Test), Week 44, and Week 48 (Pre&Post GnRHa Stim Test)
Primary	Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 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.	6 months
Secondary	Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels.	Percentage of subjects with suppressed serum LH concentrations(<4 IU/L) 30 minutes post GnRHa stimulation test at all assessed timepoints.	Week 12, Week 24, Week 36, and Week 48
Secondary	Changes in Height Velocity (Growth Rate)	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].	Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Secondary	Bone Age Ratio to Chronological Age at Time of Measurement	Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.	Week 24 and Week 48
Secondary	Percent Change From Baseline in Height	The percent change from baseline in height at each available post-baseline measurement. Percent change is defined as (((change from Baseline)/(Baseline)) x 100).	Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Secondary	Tanner Scores: Boys - Development of External Genitalia	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.	Baseline, Week 12, Week 24, Week 36, and Week 48
Secondary	Tanner Scores: Boys - Development of External Genitalia (Change From Baseline)	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.	Week 12, Week 24, Week 36, and Week 48
Secondary	Tanner Scores: Boys and Girls - Pubic Hair	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.	Baseline, Week 12, Week 24, Week 36, and Week 48
Secondary	Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline)	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.	Week 12, Week 24, Week 36, and Week 48
Secondary	Tanner Scores: Girls - Breast Development	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.	Baseline, Week 12, Week 24, Week 36, and Week 48
Secondary	Tanner Scores: Girls - Breast Development (Change From Baseline)	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.	Week 12, Week 24, Week 36, and Week 48