Central Precocious Puberty (CPP), Depot Formulation, GnRH Analog, Gonadotrophin-releasing Hormone Agonist (GnRHa), Gonadotrophin-releasing Hormone (GnRH), Leuprolide Acetate, Lupron, Luteinizing Hormone (LH), Pediatrics Central Precocious Puberty, Precocious, Suppression of LH, Tanner Staging
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGLeuprolide Acetate 3 Month Depot
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Day 1, Months 6, 12, 24, and 36 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Months 6, 9, 12, 24, 30, and 36 | 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. |
| Percentage of Male Participants With Suppression of Basal Testosterone | Day 1, Months 3, 6, 9, 12, 24, 30, and 36 | 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. |
| Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Baseline of the lead-in study L-CP07-167, Day 1, Months 6, 12, 24, and 36 | 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. |
| Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Day 1, Months 3, 6, 9, 12, and 24 | 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. |
| Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36 | 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. |
| Change From Baseline in Growth Rate | 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 | 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. |
| Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Baseline (of the lead-in study L-CP07-167), and Day 1, Months 12, 24, and 36 | 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). |
| Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36 | 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. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants who successfully completed and showed maintenance of luteinizing hormone suppression through the 6-month treatment period of the lead-in study L-CP07-167 (NCT00635817) received the same treatment in this study that they were previously assigned in the lead-in study.
Pre-assignment details
At the end of the Treatment Period, participants who completed the study or prematurely discontinued from the study could enter the Safety Follow-Up Period.
Participants by arm
| Arm | Count |
|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg Twelve intramuscular injections of leuprolide acetate for depot suspension 11.25 mg administered 3 months apart. | 34 |
| Leuprolide Acetate 3M Depot 30 mg Twelve intramuscular injections of leuprolide acetate for depot suspension 30 mg administered 3 months apart. | 38 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Safety Follow-up Period (12 Weeks) | No Longer Needed Treatment | 0 | 1 |
| Treatment Period (36 Months) | Lost to Follow-up | 1 | 0 |
| Treatment Period (36 Months) | Not Adequately Suppressed on Therapy | 3 | 0 |
| Treatment Period (36 Months) | Other | 2 | 2 |
| Treatment Period (36 Months) | Personal reasons | 2 | 2 |
| Treatment Period (36 Months) | Protocol Violation | 1 | 1 |
| Treatment Period (36 Months) | Ready to enter puberty based on age | 13 | 15 |
| Treatment Period (36 Months) | Therapeutic Failure | 1 | 1 |
| Treatment Period (36 Months) | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Leuprolide Acetate 3M Depot 11.25 mg | Leuprolide Acetate 3M Depot 30 mg | Total |
|---|---|---|---|
| Age, Continuous | 8.50 years STANDARD_DEVIATION 1.71 | 8.45 years STANDARD_DEVIATION 1.52 | 8.47 years STANDARD_DEVIATION 1.6 |
| Sex: Female, Male Female | 32 Participants | 33 Participants | 65 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 34 | 31 / 38 |
| serious Total, serious adverse events | 1 / 34 | 0 / 38 |
Outcome results
Primary
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.
Time frame: Day 1, Months 6, 12, 24, and 36
Population: Intention-to-treat, defined as patients who received at least 1 dose of study drug with at least 1 post-baseline measurement of any maintenance of suppression variable, \& did not prematurely discontinue in the 1st 30 days due to inadequate suppression at Month 6 of the lead-in study. N= the number of patients with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Day 1 [N= 32, 37] | 96.9 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Month 6 [N=32, 36] | 93.8 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Month 12 [N=31, 32] | 90.3 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Month 24 [N=16, 18] | 87.5 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Month 36 [N=9, 11] | 77.8 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Final Visit [N=33, 36] | 93.9 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Month 36 [N=9, 11] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Day 1 [N= 32, 37] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Month 24 [N=16, 18] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Month 6 [N=32, 36] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Final Visit [N=33, 36] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone | Month 12 [N=31, 32] | 96.9 percentage of participants |
Secondary
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.
Time frame: 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
Population: Intention-to-treat with available growth rate data. N = participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | Change From Baseline in Growth Rate | Change from Baseline at Final Visit [N=32, 38] | -2.27 cm/year | Standard Deviation 3.78 |
| Leuprolide Acetate 3M Depot 11.25 mg | Change From Baseline in Growth Rate | Baseline [N=32, 38] | 7.2 cm/year | Standard Deviation 3.96 |
| Leuprolide Acetate 3M Depot 11.25 mg | Change From Baseline in Growth Rate | Change from Baseline at Day 1 [N=32, 38] | -1.67 cm/year | Standard Deviation 3.9 |
| Leuprolide Acetate 3M Depot 11.25 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 6 [N=32, 37] | -1.66 cm/year | Standard Deviation 3.78 |
| Leuprolide Acetate 3M Depot 11.25 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 12 [N=28, 32] | -1.99 cm/year | Standard Deviation 3.9 |
| Leuprolide Acetate 3M Depot 11.25 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 18 [N=18, 23] | -2.21 cm/year | Standard Deviation 4.29 |
| Leuprolide Acetate 3M Depot 11.25 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 24 [N=15, 19] | -2.36 cm/year | Standard Deviation 4.85 |
| Leuprolide Acetate 3M Depot 11.25 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 30 [N=11, 17] | -1.86 cm/year | Standard Deviation 5.45 |
| Leuprolide Acetate 3M Depot 11.25 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 36 [N=8, 13] | -2.64 cm/year | Standard Deviation 5.93 |
| Leuprolide Acetate 3M Depot 30 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 30 [N=11, 17] | -2.13 cm/year | Standard Deviation 2.33 |
| Leuprolide Acetate 3M Depot 30 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 18 [N=18, 23] | -2.06 cm/year | Standard Deviation 2.4 |
| Leuprolide Acetate 3M Depot 30 mg | Change From Baseline in Growth Rate | Baseline [N=32, 38] | 7.53 cm/year | Standard Deviation 2.81 |
| Leuprolide Acetate 3M Depot 30 mg | Change From Baseline in Growth Rate | Change from Baseline at Final Visit [N=32, 38] | -2.64 cm/year | Standard Deviation 2.65 |
| Leuprolide Acetate 3M Depot 30 mg | Change From Baseline in Growth Rate | Change from Baseline at Day 1 [N=32, 38] | -1.65 cm/year | Standard Deviation 3.43 |
| Leuprolide Acetate 3M Depot 30 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 24 [N=15, 19] | -1.59 cm/year | Standard Deviation 2.2 |
| Leuprolide Acetate 3M Depot 30 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 6 [N=32, 37] | -2.04 cm/year | Standard Deviation 2.95 |
| Leuprolide Acetate 3M Depot 30 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 36 [N=8, 13] | -2.19 cm/year | Standard Deviation 2.41 |
| Leuprolide Acetate 3M Depot 30 mg | Change From Baseline in Growth Rate | Change from Baseline at Month 12 [N=28, 32] | -2.28 cm/year | Standard Deviation 2.88 |
Secondary
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.
Time frame: Baseline of the lead-in study L-CP07-167, Day 1, Months 6, 12, 24, and 36
Population: Intention-to-treat. N = the number of participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Month 6 [N=32, 36] | 2.22 mIU/mL | Standard Deviation 1.16 |
| Leuprolide Acetate 3M Depot 11.25 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Month 24 [N=14, 18] | 1.67 mIU/mL | Standard Deviation 0.97 |
| Leuprolide Acetate 3M Depot 11.25 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Day 1 [N=32, 37] | 2.00 mIU/mL | Standard Deviation 1.03 |
| Leuprolide Acetate 3M Depot 11.25 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Month 36 [N=7, 11] | 1.51 mIU/mL | Standard Deviation 0.85 |
| Leuprolide Acetate 3M Depot 11.25 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Month 12 [N=31, 32] | 2.24 mIU/mL | Standard Deviation 1.2 |
| Leuprolide Acetate 3M Depot 11.25 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Final Visit [N=33, 36] | 1.81 mIU/mL | Standard Deviation 1.13 |
| Leuprolide Acetate 3M Depot 11.25 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Baseline [N=33, 38] | 21.89 mIU/mL | Standard Deviation 38.46 |
| Leuprolide Acetate 3M Depot 30 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Final Visit [N=33, 36] | 1.15 mIU/mL | Standard Deviation 0.74 |
| Leuprolide Acetate 3M Depot 30 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Baseline [N=33, 38] | 10.16 mIU/mL | Standard Deviation 12.66 |
| Leuprolide Acetate 3M Depot 30 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Day 1 [N=32, 37] | 1.49 mIU/mL | Standard Deviation 0.86 |
| Leuprolide Acetate 3M Depot 30 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Month 6 [N=32, 36] | 1.62 mIU/mL | Standard Deviation 0.82 |
| Leuprolide Acetate 3M Depot 30 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Month 12 [N=31, 32] | 1.58 mIU/mL | Standard Deviation 1.02 |
| Leuprolide Acetate 3M Depot 30 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Month 24 [N=14, 18] | 0.88 mIU/mL | Standard Deviation 0.58 |
| Leuprolide Acetate 3M Depot 30 mg | Mean Peak-stimulated Luteinizing Hormone Concentration by Visit | Month 36 [N=7, 11] | 0.91 mIU/mL | Standard Deviation 0.49 |
Secondary
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.
Time frame: Day 1, Months 3, 6, 9, 12, and 24
Population: Intention-to-treat female population. N = the number of participants with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 6 [N=26, 25] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 12 [N=10, 12] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 3 [N=29, 33] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 24 [N=1, 0] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 9 [N=18, 18] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Final Visit [N=31, 33] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Day 1 [N=28, 30] | 96.4 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Final Visit [N=31, 33] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Day 1 [N=28, 30] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 3 [N=29, 33] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 6 [N=26, 25] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 9 [N=18, 18] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 12 [N=10, 12] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 1) | Month 24 [N=1, 0] | NA percentage of participants |
Secondary
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.
Time frame: Months 6, 9, 12, 24, 30, and 36
Population: Intention-to-treat female population. N = the number of participants with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 12 [N=20, 15] | 45.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 30 [N=9, 15] | 33.3 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 9 [N=13, 10] | 61.5 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 36 [N=7, 11] | 28.6 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 24 [N=14, 15] | 50.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Final Visit [N=24, 26] | 29.2 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 6 [N=4, 6] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Final Visit [N=24, 26] | 30.8 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 6 [N=4, 6] | 83.3 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 9 [N=13, 10] | 40.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 12 [N=20, 15] | 60.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 24 [N=14, 15] | 53.3 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 30 [N=9, 15] | 26.7 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of Basal Estradiol (Assay 2) | Month 36 [N=7, 11] | 36.4 percentage of participants |
Secondary
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.
Time frame: Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36
Population: Intention-to-treat female population, excluding participants who entered the study at Stage 5. N = the number of participants with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Day 1 [N= 31, 31] | 90.3 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 3 [N=29, 31] | 86.2 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 6 [N=31, 30] | 90.3 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 9 [N=31, 28] | 87.1 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 12 [N=28, 26] | 85.7 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 18 [N=17, 20] | 82.4 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 24 [N=14, 16] | 78.6 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 30 [N=10, 16] | 90.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 36 [N=8, 12] | 87.5 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Final Visit [N=31, 31] | 83.9 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 30 [N=10, 16] | 68.8 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Day 1 [N= 31, 31] | 83.9 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 18 [N=17, 20] | 75.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 3 [N=29, 31] | 87.1 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Final Visit [N=31, 31] | 71.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 6 [N=31, 30] | 80.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 24 [N=14, 16] | 75.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 9 [N=31, 28] | 75.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 36 [N=8, 12] | 66.7 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Female Participants With Suppression of the Physical Signs of Puberty (Breast Development) | Month 12 [N=28, 26] | 80.8 percentage of participants |
Secondary
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.
Time frame: Day 1, Months 3, 6, 9, 12, 24, 30, and 36
Population: Intention-to-treat male population. N = the number of participants with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 3 [N=2, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 24 [N=1, 3] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 9 [N=2, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 30 [N=0, 1] | NA percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 6 [N=2, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 36 [N=0, 1] | NA percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 12 [N=1, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Final Visit [N=2, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Day 1 [N= 2, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Final Visit [N=2, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Day 1 [N= 2, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 3 [N=2, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 6 [N=2, 5] | 80.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 9 [N=2, 5] | 80.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 12 [N=1, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 24 [N=1, 3] | 66.7 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 30 [N=0, 1] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of Basal Testosterone | Month 36 [N=0, 1] | 100.0 percentage of participants |
Secondary
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.
Time frame: Baseline (of the lead-in study L-CP07-167), Day 1, Months 3, 6, 9, 12, 18, 24, 30, and 36
Population: Intention-to-treat male population, excluding participants who entered the study at Stage 5. N = the number of participants with available data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Day 1 [N= 2, 5] | 50.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 3 [N=2, 5] | 50.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 6 [N=2, 5] | 50.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 9 [N=2, 5] | 50.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 12 [N=1, 5] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 18 [N=1, 3] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 24 [N=1, 3] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 30 [N=1, 1] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 36 [N=0, 1] | NA percentage of participants |
| Leuprolide Acetate 3M Depot 11.25 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Final Visit [N=2, 5] | 50.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 30 [N=1, 1] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Day 1 [N= 2, 5] | 40.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 18 [N=1, 3] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 3 [N=2, 5] | 60.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Final Visit [N=2, 5] | 20.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 6 [N=2, 5] | 60.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 24 [N=1, 3] | 33.3 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 9 [N=2, 5] | 40.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 36 [N=0, 1] | 100.0 percentage of participants |
| Leuprolide Acetate 3M Depot 30 mg | Percentage of Male Participants With Suppression of the Physical Signs of Puberty (Testicular Volume and Genital Development) | Month 12 [N=1, 5] | 60.0 percentage of participants |
Secondary
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).
Time frame: Baseline (of the lead-in study L-CP07-167), and Day 1, Months 12, 24, and 36
Population: Intention-to-treat with available bone age data. N = participants with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprolide Acetate 3M Depot 11.25 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Month 12 [N=32, 32] | 0.52 ratio | Standard Deviation 0.33 |
| Leuprolide Acetate 3M Depot 11.25 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Month 36 [N=5, 11] | 0.43 ratio | Standard Deviation 0.15 |
| Leuprolide Acetate 3M Depot 11.25 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Month 24 [N=14, 17] | 0.53 ratio | Standard Deviation 0.3 |
| Leuprolide Acetate 3M Depot 11.25 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Final Visit [N=33, 32] | 0.48 ratio | Standard Deviation 0.28 |
| Leuprolide Acetate 3M Depot 11.25 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Day 1 [N=32, 37] | 0.51 ratio | Standard Deviation 0.56 |
| Leuprolide Acetate 3M Depot 30 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Final Visit [N=33, 32] | 0.56 ratio | Standard Deviation 0.3 |
| Leuprolide Acetate 3M Depot 30 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Day 1 [N=32, 37] | 1.02 ratio | Standard Deviation 1.27 |
| Leuprolide Acetate 3M Depot 30 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Month 12 [N=32, 32] | 0.62 ratio | Standard Deviation 0.37 |
| Leuprolide Acetate 3M Depot 30 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Month 24 [N=14, 17] | 0.72 ratio | Standard Deviation 0.34 |
| Leuprolide Acetate 3M Depot 30 mg | Ratio of Change From Baseline in Bone Age/Change From Baseline in Chronological Age | Month 36 [N=5, 11] | 0.64 ratio | Standard Deviation 0.3 |