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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02452931
Recruitment Status : Completed
First Posted : May 25, 2015
Results First Posted : May 20, 2020
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Precocious Puberty, Central Drug: Leuprolide Acetate 45 mg Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 31, 2015
Actual Primary Completion Date : September 5, 2018
Actual Study Completion Date : September 5, 2018


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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].

  3. 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.

  4. 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).

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.


Other Outcome Measures:
  1. 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.

  2. Bone Age [ Time Frame: Baseline, Week 24, and Week 48 ]
    Bone Age at each available measurement point.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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.

  8. 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.

  9. 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



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Ages Eligible for Study:   2 Years to 9 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02452931


Locations
Show Show 20 study locations
Sponsors and Collaborators
Tolmar Inc.
Investigators
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Study Director: Peggy Schorr orphan reach USA, LLC
  Study Documents (Full-Text)

Documents provided by Tolmar Inc.:
Study Protocol  [PDF] August 25, 2015
Statistical Analysis Plan  [PDF] September 4, 2018

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Responsible Party: Tolmar Inc.
ClinicalTrials.gov Identifier: NCT02452931    
Obsolete Identifiers: NCT02811471
Other Study ID Numbers: TOL2581A
First Posted: May 25, 2015    Key Record Dates
Results First Posted: May 20, 2020
Last Update Posted: June 2, 2020
Last Verified: May 2020
Additional relevant MeSH terms:
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Puberty, Precocious
Gonadal Disorders
Endocrine System Diseases
Leuprolide
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents