Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty

Study Overview
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Brief Summary
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The purpose of this extension study is to determine if leuprolide acetate (11.25 mg and 30 mg) is safe in treating children with Central Precocious Puberty over a longer period of time (36 months).

Detailed Description
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This study includes a 36-month Study Drug Treatment Period (3-month treatment cycles), and a Safety Follow-up Period (12 weeks following the Month 36 visit). Participants will receive a total of twelve injections of the same treatment they received in the lead-in study, L-CP07-167 (NCT00635817) either leuprolide acetate 11.25 mg or 30 mg depot formulation. Each injection will be administered 3 months apart for up to 36 months of treatment. Study visits will occur on Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30 and 33 (1st through the 12th leuprolide acetate depot injections, respectively), Month 36, and 12 weeks later for the Safety Follow-up Visit.

Official Title
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A 36 Month, Multi-Center, Open-Label Extension Study to Evaluate the Safety of Leuprolide Acetate 11.25 mg and 30 mg Formulations in Children With Central Precocious Puberty

Conditions
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Precocious, Leuprolide Acetate, Luteinizing Hormone (LH), Gonadotrophin-releasing Hormone Agonist (GnRHa), Tanner Staging, Depot Formulation, Suppression of LH, Central Precocious Puberty (CPP), Gonadotrophin-releasing Hormone (GnRH), Lupron, GnRH Analog, Pediatrics Central Precocious Puberty

Intervention / Treatment
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* Drug: Leuprolide Acetate 3 Month Depot


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject completed the Treatment Period of the lead-in study, L-CP07-167 (NCT00635817), and has documented luteinizing hormone suppression as evidenced by peak-stimulated luteinizing hormone <4 mIU/mL at the Month 6 study visit of the lead-in study. Demonstrated suppression of the physical signs of puberty at Month 6 of the lead-in study. Subject is expected to receive at least 12 months of therapy to treat Central Precocious Puberty after study entry. In general good health with no uncontrolled, clinically significant disease which would interfere with bone maturation or mask the objectives of this protocol as assessed by the investigator. Exclusion Criteria: Incomplete precocious puberty, peripheral precocious puberty or evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid and gonadal function (other than premature secretion of gonadotropins) not adequately controlled, unstable intracranial tumors except hamartoma. Bone age ≥14 years for girls and ≥15 years for boys (based on the Month 6 lead in study, L-CP07-167, radiographic results). Has an abnormal laboratory value suggesting a clinically significant underlying disease or condition. Chronic illness requiring treatment that may interfere with growth, ie, chronic steroid use, renal failure, moderate to severe scoliosis. Current therapy with medroxyprogesterone acetate. Current therapy with growth hormone. Current therapy with insulin-like growth factor-1 (IGF-1). Current use of an estrogen preparation. Any concomitant medical condition that, in the opinion of the investigator, may expose a subject to an unacceptable level of safety risk or that affects subject compliance. Subject has a positive pregnancy test.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Leuprolide Acetate 3M Depot 11.25 mg<br>Twelve intramuscular injections of leuprolide acetate for depot suspension 11.25 mg administered 3 months (3M) apart. | Drug: Leuprolide Acetate 3 Month Depot<br> <br> * Other names: Leuprorelin acetate;|
| Experimental: Leuprolide Acetate 3M Depot 30 mg<br>Twelve intramuscular injections of leuprolide acetate for depot suspension 30 mg administered 3 months apart. | Drug: Leuprolide Acetate 3 Month Depot<br> <br> * Other names: Leuprorelin acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Luteinizing Hormone (LH) suppression is defined as peak-stimulated LH < 4 mIU/mL. Peak-stimulated LH refers to the maximum LH concentration measured 30 and 60 minutes after a gonadotropin-releasing hormone agonist (GnRHa) stimulation test. Participants who failed suppression at previous visit and prematurely discontinued were counted as having failed future visits also. Final visit is the participant's last visit closest to Month 36. | Day 1, Months 6, 12, 24, and 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | The percentage of female participants with suppression of basal estradiol to prepubertal levels, defined as estradiol < 20 pg/mL. The estradiol assay was changed in June of 2010, and the lower limit of quantitation (LLOQ) was increased from 1 pg/mL to 10 pg/mL. This outcome measure reports data for assays performed before this change occurred, with an LLOQ of 1 pg/mL. Final visit is the participant's last visit closest to Month 36. | Day 1, Months 3, 6, 9, 12, and 24 | 
| Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | The percentage of female participants with suppression of basal estradiol to prepubertal levels, defined as estradiol < 20 pg/mL. The estradiol assay was changed in June of 2010, and the lower limit of quantitation (LLOQ) was increased from 1 pg/mL to 10 pg/mL. This outcome measure reports data for assays performed after this change occurred, with an LLOQ of 10 pg/mL. Final visit is the participant's last visit closest to Month 36. | Months 6, 9, 12, 24, 30, and 36 | 
| Percentage of Male Participants With Suppression of Basal Testosterone | The percentage of male participants with suppression of basal testosterone to prepubertal levels, defined as testosterone < 30 ng/dL. Final visit is the participant's last visit closest to Month 36. | Day 1, Months 3, 6, 9, 12, 24, 30, and 36 | 
| Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Peak-stimulated luteinizing hormone refers to the maximum luteinizing hormone concentration measured 30 and 60 minutes after a gonadotropin-releasing hormone agonist (GnRHa) stimulation test. Final visit is the participant's last visit closest to Month 36. | Baseline of the lead-in study L-CP07-167, Day 1, Months 6, 12, 24, and 36 | 
| Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | The percentage of female participants with suppression of breast development. Breast development was rated from Stage 1 (early development) through Stage 5 (full development) according to a modified Tanner Staging pictogram. Suppression of breast development is defined as regression or no progression of breast development from Baseline (of the lead-in study L-CP07-167) according to pubertal staging. Girls entering the study with fully developed breasts (Stage 5) were excluded from this analysis. Final visit is the participant's last visit closest to Month 36. | Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36 | 
| Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | The percentage of male participants with suppression of testicular volume and genital staging. Testicular volume was calculated from the length, width and height of each testicle measured by ultrasound. External genital development (testes and penis) was rated from Stage 1 (early development) through Stage 5 (full development) according to a modified Tanner Staging pictogram. Suppression is defined as regression or no progression in both testicular volume and genital staging from Baseline (of the lead-in study L-CP07-167) according to pubertal staging. Boys entering the study with fully developed genitals (Stage 5) were excluded from this analysis. Final visit is the participant's last visit closest to Month 36. | Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36 | 
| Change From Baseline in Growth Rate | Baseline growth rate was the growth rate in the one year prior to Day 1 of the lead-in study L-CP07-167. Growth rates were calculated as the ratio of the change in height to the change in chronological age with an approximate 6-month interval for Day 1, Months 6, 12, 18, 24, 30, 36 and the Final Treatment Visit. | Baseline (the 1 year prior to the start of treatment in the lead-in study), and Day 1, Months 6, 12, 18, 24, 30, and 36 | 
| Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Bone age was determined by left hand/wrist bone age radiographs that were evaluated using the Fels Method by a central reader. The ratio of change from Baseline in bone age (BA)/change from Baseline in chronological age (CA) was calculated using the following formula: (BA at Post-baseline Treatment Visit - BA at Baseline) / (CA at Post-baseline Treatment Visit - CA at Baseline). | Baseline (of the lead-in study L-CP07-167), and Day 1, Months 12, 24, and 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GnRH analog, Luteinizing hormone (LH), Gonadotrophin-releasing hormone agonist(GnRHa), Suppression of LH, Gonadotrophin-releasing hormone (GnRH), CPP, Leuprolide acetate, Central Precocious Puberty, Depot formulation, Lupron, Tanner staging, Pediatrics