Study of Leuprolide Acetate Injectable Suspension in the Treatment of Central Precocious Puberty
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| ClinicalTrials.gov Identifier: NCT02452931 |
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Recruitment Status :
Completed
First Posted : May 25, 2015
Results First Posted : May 20, 2020
Last Update Posted : June 2, 2020
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Sponsor:
Tolmar Inc.
Information provided by (Responsible Party):
Tolmar Inc.
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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 |
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 : | 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 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Familial male-limited precocious puberty
Central precocious puberty
MedlinePlus related topics:
Puberty
| Arm | Intervention/treatment |
|---|---|
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Experimental: Assigned Intervention
Leuprolide acetate 45 mg will be administered as a subcutaneous injection at 6-month intervals for the 12 month study period.
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Drug: Leuprolide Acetate 45 mg
Subcutaneous injection |
Primary Outcome Measures :
- 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 :
- 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.
- 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].
- 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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:
- 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.
- Bone Age [ Time Frame: Baseline, Week 24, and Week 48 ]Bone Age at each available measurement point.
- 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.
- 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.
- 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).
- 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.
- 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.
- 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.
- 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 20 study locations
Sponsors and Collaborators
Tolmar Inc.
Investigators
| Study Director: | Peggy Schorr | orphan reach USA, LLC |
Study Documents (Full-Text)
Documents provided by Tolmar Inc.:
Documents provided by Tolmar Inc.:
Study Protocol [PDF] August 25, 2015
Statistical Analysis Plan [PDF] September 4, 2018
| 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 |