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

May 19, 2020 updated by: Tolmar Inc.

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
64

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1425EFD
        • Hospital de Niños
  • Canada
      • Quebec, Canada, G1V 4G2
        • CHU de Quebec-Universite Laval
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • University of Calgary, Alberta Children's Hospital
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill University Health Centre
  • Chile
    • Metropolitana
      • Santiago, Metropolitana, Chile, 8330074
        • Pontificia Universidad Catolica de Chile
      • Santiago, Metropolitana, Chile, 8360160
        • Instituto de Investigaciones Materno Infantil (IDIMI)
    • Second Region
      • Antofagasta, Second Region, Chile, 1270001
        • Hospital Regional de Antofagasta Leonardo Guzman
  • Mexico
      • Durango, Mexico, 34000
        • Instituto de Investigaciones Aplicadas a la Neurociencia, A.C.
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 64460
        • Hospital Unversitario "Dr. Jose Eleuterio Gonzalez"
  • New Zealand
      • Auckland, New Zealand, 1023
        • The Liggins Institute, University of Auckland
  • United States
    • California
      • San Diego, California, United States, 92123
        • University of California, San Diego
    • Florida
      • Hollywood, Florida, United States, 33021
        • Joe DiMaggio Children's Hospital
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children at Indiana University Health
    • Minnesota
      • Minneapolis, Minnesota, United States, 55414
        • University of Minnesota
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center, Endocrine
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74135
        • University of Oklahoma College of Medicine
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's
      • Tacoma, Washington, United States, 98405
        • MultiCare Institute for Research and Innovation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 9 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Assigned Intervention
Leuprolide acetate 45 mg will be administered as a subcutaneous injection at 6-month intervals for the 12 month study period.
Drug: Leuprolide Acetate 45 mg
Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months.
Time Frame: 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels.
Time Frame: 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.
Week 12, Week 24, Week 36, and Week 48
Changes in Height Velocity (Growth Rate)
Time Frame: 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].
Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Bone Age Ratio to Chronological Age at Time of Measurement
Time Frame: Week 24 and Week 48
Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.
Week 24 and Week 48
Percent Change From Baseline in Height
Time Frame: 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).
Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Tanner Scores: Boys - Development of External Genitalia
Time Frame: 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.
Baseline, Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Boys - Development of External Genitalia (Change From Baseline)
Time Frame: 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.
Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Boys and Girls - Pubic Hair
Time Frame: 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.
Baseline, Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline)
Time Frame: 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.
Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Girls - Breast Development
Time Frame: 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.
Baseline, Week 12, Week 24, Week 36, and Week 48
Tanner Scores: Girls - Breast Development (Change From Baseline)
Time Frame: 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.
Week 12, Week 24, Week 36, and Week 48

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Height
Time Frame: Screening, Baseline, Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
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
Bone Age
Time Frame: Baseline, Week 24, and Week 48
Bone Age at each available measurement point.
Baseline, Week 24, and Week 48
Bone Age Progression
Time Frame: Week 24 and Week 48
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
Bone Age Ratio to Chronological Age at Time of Measurement (Percent Change From Baseline)
Time Frame: Week 24 and Week 48
Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.
Week 24 and Week 48
Bone Age Ratio to Chronological Age at Start of Study (Percent Change From Baseline)
Time Frame: Week 24 and Week 48
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
Bone Age Ratio to Chronological Age at Start of Study
Time Frame: Baseline, Week 24, and Week 48
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
GnRH Antagonist Evaluation
Time Frame: Week 2, Week 4, Week 12, Week 20, Week 24, Week 26, Week 36, Week 44, and Week 48
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
Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels.
Time Frame: Week 12, Week 24, Week 36, and Week 48
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
Changes in the Ratio of LH/FSH
Time Frame: 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)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tolmar Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Peggy Schorr, orphan reach USA, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 31, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 5, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 5, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 5, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 25, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 2, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TOL2581A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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