Precocious Puberty, Central
Conditions
Brief summary
This study determines the effectiveness of leuprolide acetate 45 mg for injectable suspension for treatment of children with Central Precocious Puberty.
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.
Interventions
DRUGLeuprolide Acetate 45 mg
Subcutaneous injection
Sponsors
Tolmar Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 9 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months. | 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in Height Velocity (Growth Rate) | 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 / \[(number of weeks since week 24)/52\]. |
| Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels. | 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. |
| Bone Age Ratio to Chronological Age at Time of Measurement | 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 | 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 | 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) | 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 | 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) | 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 | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Bone Age Progression | 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) | 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) | 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 | 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 | 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. | 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 | 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 |
| Bone Age | Baseline, Week 24, and Week 48 | Bone Age at each available measurement point. |
| Height | 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. |
Countries
Argentina, Canada, Chile, Mexico, New Zealand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Assigned Intervention Leuprolide acetate 45 mg will be administered as a subcutaneous injection at 6-month intervals for the 12 month study period.
Leuprolide Acetate 45 mg: Subcutaneous injection | 64 |
| Total | 64 |
Baseline characteristics
| Characteristic | Assigned Intervention |
|---|---|
| Age, Continuous | 7.5 years STANDARD_DEVIATION 0.89 |
| Luteinizing Hormone | 23.46 IU/L STANDARD_DEVIATION 24.282 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 5 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 36 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Not hispanic or Latino | 28 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized Unwilling to Provide | 1 Participants |
| Race/Ethnicity, Customized White | 34 Participants |
| Region of Enrollment Argentina | 13 participants |
| Region of Enrollment Canada | 2 participants |
| Region of Enrollment Chile | 9 participants |
| Region of Enrollment Mexico | 7 participants |
| Region of Enrollment New Zealand | 2 participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 62 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 64 |
| other Total, other adverse events | 55 / 64 |
| serious Total, serious adverse events | 1 / 64 |
Outcome results
Primary
Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 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.
Time frame: 6 months
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Assigned Intervention | Percentage of Participants With Suppression of Peak-Stimulated Luteinizing Hormone at 6 Months. | 54 Participants |
Secondary
Bone Age Ratio to Chronological Age at Time of Measurement
Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.
Time frame: Week 24 and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Bone Age Ratio to Chronological Age at Time of Measurement | Baseline | 1.39 Ratio | Standard Deviation 0.16 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Time of Measurement | Visit 5, Week 24 | 1.34 Ratio | Standard Deviation 0.138 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Time of Measurement | End of Treatment, Week 48 | 1.32 Ratio | Standard Deviation 0.143 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Time of Measurement | Minimum Post-baseline Value | 1.30 Ratio | Standard Deviation 0.138 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Time of Measurement | Maximum Post-baseline Value | 1.36 Ratio | Standard Deviation 0.138 |
Secondary
Changes in Height Velocity (Growth Rate)
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 / \[(number of weeks since week 24)/52\].
Time frame: Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Changes in Height Velocity (Growth Rate) | Visit 2, Week 4 | 8.89 cm/year | Standard Deviation 13.128 |
| Assigned Intervention | Changes in Height Velocity (Growth Rate) | Visit 3, Week 12 | 8.30 cm/year | Standard Deviation 4.782 |
| Assigned Intervention | Changes in Height Velocity (Growth Rate) | Visit 4, Week 20 | 6.66 cm/year | Standard Deviation 3.155 |
| Assigned Intervention | Changes in Height Velocity (Growth Rate) | Visit 5, Week 24 | 6.90 cm/year | Standard Deviation 3.074 |
| Assigned Intervention | Changes in Height Velocity (Growth Rate) | Visit 6, Week 36 | 6.48 cm/year | Standard Deviation 2.272 |
| Assigned Intervention | Changes in Height Velocity (Growth Rate) | Visit 7, Week 44 | 6.23 cm/year | Standard Deviation 1.953 |
| Assigned Intervention | Changes in Height Velocity (Growth Rate) | End of Treatment, Week 48 | 6.37 cm/year | Standard Deviation 1.893 |
| Assigned Intervention | Changes in Height Velocity (Growth Rate) | End of Treatment, Week 48: Change from Week 24 | 5.79 cm/year | Standard Deviation 2.213 |
Secondary
Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels.
Percentage of subjects with suppressed serum LH concentrations(\<4 IU/L) 30 minutes post GnRHa stimulation test at all assessed timepoints.
Time frame: Week 12, Week 24, Week 36, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Assigned Intervention | Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels. | Visit 3, Week 12 | 51 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels. | Visit 5, Week 24 | 54 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels. | Visit 6, Week 36 | 50 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of Luteinizing Hormone Measured by Blood Levels. | End of Treatment, Week 48 | 50 Participants |
Secondary
Percent Change From Baseline in Height
The percent change from baseline in height at each available post-baseline measurement. Percent change is defined as (((change from Baseline)/(Baseline)) x 100).
Time frame: Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Percent Change From Baseline in Height | Visit 3, Week 12 | 1.4 Percent change | Standard Deviation 0.82 |
| Assigned Intervention | Percent Change From Baseline in Height | Visit 2, Week 4 | 0.5 Percent change | Standard Deviation 0.78 |
| Assigned Intervention | Percent Change From Baseline in Height | Visit 4, Week 20 | 1.9 Percent change | Standard Deviation 0.89 |
| Assigned Intervention | Percent Change From Baseline in Height | Visit 5, Week 24 | 2.3 Percent change | Standard Deviation 1.06 |
| Assigned Intervention | Percent Change From Baseline in Height | Visit 6, Week 36 | 3.3 Percent change | Standard Deviation 1.17 |
| Assigned Intervention | Percent Change From Baseline in Height | Visit 7, Week 44 | 3.9 Percent change | Standard Deviation 1.26 |
| Assigned Intervention | Percent Change From Baseline in Height | End of Treatment, Week 48 | 4.3 Percent change | Standard Deviation 1.34 |
Secondary
Tanner Scores: Boys and Girls - Pubic Hair
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.
Time frame: Baseline, Week 12, Week 24, Week 36, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Tanner Scores: Boys and Girls - Pubic Hair | Baseline | 2.3 Score on a scale | Standard Deviation 0.81 |
| Assigned Intervention | Tanner Scores: Boys and Girls - Pubic Hair | Visit 3, Week 12 | 2.4 Score on a scale | Standard Deviation 0.89 |
| Assigned Intervention | Tanner Scores: Boys and Girls - Pubic Hair | Visit 5, Week 24 | 2.5 Score on a scale | Standard Deviation 0.92 |
| Assigned Intervention | Tanner Scores: Boys and Girls - Pubic Hair | Visit 6, Week 36 | 2.3 Score on a scale | Standard Deviation 0.94 |
| Assigned Intervention | Tanner Scores: Boys and Girls - Pubic Hair | End of Treatment, Week 48 | 2.4 Score on a scale | Standard Deviation 0.95 |
Secondary
Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline)
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.
Time frame: Week 12, Week 24, Week 36, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline) | Visit 3, Week 12 | 0.1 Score on a scale | Standard Deviation 0.56 |
| Assigned Intervention | Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline) | Visit 5, Week 24 | 0.1 Score on a scale | Standard Deviation 0.59 |
| Assigned Intervention | Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline) | Visit 6, Week 36 | 0.1 Score on a scale | Standard Deviation 0.6 |
| Assigned Intervention | Tanner Scores: Boys and Girls - Pubic Hair (Change From Baseline) | End of Treatment, Week 48 | 0.1 Score on a scale | Standard Deviation 0.58 |
Secondary
Tanner Scores: Boys - Development of External Genitalia
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.
Time frame: Baseline, Week 12, Week 24, Week 36, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Tanner Scores: Boys - Development of External Genitalia | Baseline | 3.0 Score on a scale | Standard Deviation 0 |
| Assigned Intervention | Tanner Scores: Boys - Development of External Genitalia | Visit 3, Week 12 | 2.5 Score on a scale | Standard Deviation 0.71 |
| Assigned Intervention | Tanner Scores: Boys - Development of External Genitalia | Visit 5, Week 24 | 2.5 Score on a scale | Standard Deviation 0.71 |
| Assigned Intervention | Tanner Scores: Boys - Development of External Genitalia | Visit 6, Week 36 | 2.5 Score on a scale | Standard Deviation 0.71 |
| Assigned Intervention | Tanner Scores: Boys - Development of External Genitalia | End of Treatment, Week 48 | 2.0 Score on a scale | Standard Deviation 0 |
Secondary
Tanner Scores: Boys - Development of External Genitalia (Change From Baseline)
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.
Time frame: Week 12, Week 24, Week 36, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Tanner Scores: Boys - Development of External Genitalia (Change From Baseline) | Visit 3, Week 12 | -0.5 Score on a scale | Standard Deviation 0.71 |
| Assigned Intervention | Tanner Scores: Boys - Development of External Genitalia (Change From Baseline) | Visit 5, Week 24 | -0.5 Score on a scale | Standard Deviation 0.71 |
| Assigned Intervention | Tanner Scores: Boys - Development of External Genitalia (Change From Baseline) | Visit 6, Week 36 | -0.5 Score on a scale | Standard Deviation 0.71 |
| Assigned Intervention | Tanner Scores: Boys - Development of External Genitalia (Change From Baseline) | End of Treatment, Week 48 | -1.0 Score on a scale | Standard Deviation 0 |
Secondary
Tanner Scores: Girls - Breast Development
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.
Time frame: Baseline, Week 12, Week 24, Week 36, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Tanner Scores: Girls - Breast Development | Baseline | 3.2 Score on a scale | Standard Deviation 0.61 |
| Assigned Intervention | Tanner Scores: Girls - Breast Development | Visit 3, Week 12 | 2.7 Score on a scale | Standard Deviation 0.9 |
| Assigned Intervention | Tanner Scores: Girls - Breast Development | Visit 5, Week 24 | 2.6 Score on a scale | Standard Deviation 1 |
| Assigned Intervention | Tanner Scores: Girls - Breast Development | Visit 6, Week 36 | 2.5 Score on a scale | Standard Deviation 0.89 |
| Assigned Intervention | Tanner Scores: Girls - Breast Development | End of Treatment, Week 48 | 2.4 Score on a scale | Standard Deviation 0.93 |
Secondary
Tanner Scores: Girls - Breast Development (Change From Baseline)
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.
Time frame: Week 12, Week 24, Week 36, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing. Tanner Stages: I (\<10yrs), II (10-11yrs), III (11-13yrs), IV (13-14yrs), V (\>14yrs).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Tanner Scores: Girls - Breast Development (Change From Baseline) | Visit 3, Week 12 | -0.5 Score on a scale | Standard Deviation 0.9 |
| Assigned Intervention | Tanner Scores: Girls - Breast Development (Change From Baseline) | Visit 5, Week 24 | -0.6 Score on a scale | Standard Deviation 0.87 |
| Assigned Intervention | Tanner Scores: Girls - Breast Development (Change From Baseline) | Visit 6, Week 36 | -0.6 Score on a scale | Standard Deviation 0.86 |
| Assigned Intervention | Tanner Scores: Girls - Breast Development (Change From Baseline) | End of Treatment, Week 48 | -0.7 Score on a scale | Standard Deviation 0.89 |
Other Pre-specified
Bone Age
Bone Age at each available measurement point.
Time frame: Baseline, Week 24, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Bone Age | Baseline | 11.01 years | Standard Deviation 1.307 |
| Assigned Intervention | Bone Age | Visit 5, Week 24 | 11.30 years | Standard Deviation 1.238 |
| Assigned Intervention | Bone Age | End of Treatment, Week 48 | 11.65 years | Standard Deviation 1.124 |
Other Pre-specified
Bone Age Progression
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.
Time frame: Week 24 and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Bone Age Progression | Visit 5, Week 24 | 2.91 percent change | Standard Deviation 4.607 |
| Assigned Intervention | Bone Age Progression | End of Treatment, Week 48 | 6.81 percent change | Standard Deviation 5.741 |
| Assigned Intervention | Bone Age Progression | Minimum Post-Baseline Value | 2.91 percent change | Standard Deviation 4.607 |
| Assigned Intervention | Bone Age Progression | Maximum Post-Baseline Value | 6.63 percent change | Standard Deviation 5.736 |
Other Pre-specified
Bone Age Ratio to Chronological Age at Start of Study
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.
Time frame: Baseline, Week 24, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Bone Age Ratio to Chronological Age at Start of Study | Baseline | 1.38 Ratio | Standard Deviation 0.158 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Start of Study | Visit 5, Week 24 | 1.42 Ratio | Standard Deviation 0.153 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Start of Study | End of Treatment, Week 48 | 1.47 Ratio | Standard Deviation 0.178 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Start of Study | Minimum Post-baseline Value | 1.42 Ratio | Standard Deviation 0.153 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Start of Study | Maximum Post-baseline Value | 1.47 Ratio | Standard Deviation 0.176 |
Other Pre-specified
Bone Age Ratio to Chronological Age at Start of Study (Percent Change From Baseline)
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).
Time frame: Week 24 and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Bone Age Ratio to Chronological Age at Start of Study (Percent Change From Baseline) | Visit 5, Week 24 | 2.91 percent change | Standard Deviation 4.607 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Start of Study (Percent Change From Baseline) | End of Treatment, Week 48 | 6.81 percent change | Standard Deviation 5.741 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Start of Study (Percent Change From Baseline) | Minimum Post-baseline Value | 2.91 percent change | Standard Deviation 4.607 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Start of Study (Percent Change From Baseline) | Maximum Post-baseline Value | 6.63 percent change | Standard Deviation 5.736 |
Other Pre-specified
Bone Age Ratio to Chronological Age at Time of Measurement (Percent Change From Baseline)
Bone Age Ratio to Chronological Age at Time of Measurement is bone age/age at bone age assessment.
Time frame: Week 24 and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Bone Age Ratio to Chronological Age at Time of Measurement (Percent Change From Baseline) | Visit 5, Week 24 | -3.25 percent change | Standard Deviation 4.382 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Time of Measurement (Percent Change From Baseline) | End of Treatment, Week 48 | -4.90 percent change | Standard Deviation 4.689 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Time of Measurement (Percent Change From Baseline) | Minimum Post-baseline Value | -6.15 percent change | Standard Deviation 3.934 |
| Assigned Intervention | Bone Age Ratio to Chronological Age at Time of Measurement (Percent Change From Baseline) | Maximum Post-baseline Value | -1.89 percent change | Standard Deviation 4.155 |
Other Pre-specified
Changes in the Ratio of LH/FSH
Changes in ratio of LH/FSH at each time point from Screening to End of Study
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)
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 4 | 0.843 Ratio | Standard Deviation 1.0004 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Screening: Pre GnRHa Stimulation Test | 0.387 Ratio | Standard Deviation 0.4675 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Screening: Post GnRHa Stimulation Test | 2.187 Ratio | Standard Deviation 1.6713 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Baseline | 0.604 Ratio | Standard Deviation 0.9851 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Baseline: 1 hr Post Inj | 2.424 Ratio | Standard Deviation 2.1534 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Baseline: 1 hr Post Inj: Change from Baseline | 1.856 Ratio | Standard Deviation 1.7277 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Baseline: 4 hr Post Inj | 2.110 Ratio | Standard Deviation 2.3939 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Baseline: 4 hr Post Inj: Change from Baseline | 1.542 Ratio | Standard Deviation 2.0932 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Baseline: 6 hr Post Inj | 1.691 Ratio | Standard Deviation 1.733 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Baseline: 6 hr Post Inj: Change from Baseline | 1.123 Ratio | Standard Deviation 1.4378 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 4: Change from Baseline | 0.233 Ratio | Standard Deviation 1.1425 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 12: Pre GnRHa Stim Test | 0.565 Ratio | Standard Deviation 0.91 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 12: Pre GnRHa Stim Test: Change from Baseline | -0.050 Ratio | Standard Deviation 1.0423 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 12: Post GnRHa Stim Test | 1.342 Ratio | Standard Deviation 1.7934 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week12: Post GnRHa Stim Test: Change from Baseline | 0.721 Ratio | Standard Deviation 1.7237 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 20 | 0.654 Ratio | Standard Deviation 0.9806 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 20: Change from Baseline | 0.068 Ratio | Standard Deviation 1.1859 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 24: Pre GnRHa Stim Test | 0.611 Ratio | Standard Deviation 0.9571 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 24: Pre GnRHa Stim Test: Change from Baseline | 0.007 Ratio | Standard Deviation 1.1818 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 24: Post GnRHa Stim Test | 1.320 Ratio | Standard Deviation 1.2843 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week24: Post GnRHa Stim Test: Change from Baseline | 0.716 Ratio | Standard Deviation 1.445 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 36: Pre GnRHa Stim Test | 0.474 Ratio | Standard Deviation 0.5249 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 36: Pre GnRHa Stim Test: Change from Baseline | -0.125 Ratio | Standard Deviation 1.0038 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 36: Post GnRHa Stim Test | 1.051 Ratio | Standard Deviation 1.413 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week36: Post GnRHa Stim Test: Change from Baseline | 0.461 Ratio | Standard Deviation 15374 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 44 | 0.517 Ratio | Standard Deviation 0.7846 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 44: Change from Baseline | -0.073 Ratio | Standard Deviation 1.0575 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 48: Pre GnRHa Stim Test | 0.557 Ratio | Standard Deviation 1.0957 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 48: Pre GnRHa Stim Test: Change from Baseline | -0.033 Ratio | Standard Deviation 1.2191 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week 48: Post GnRHa Stim Test | 1.092 Ratio | Standard Deviation 1.5655 |
| Assigned Intervention | Changes in the Ratio of LH/FSH | Week48: Post GnRHa Stim Test: Change from Baselin | 0.509 Ratio | Standard Deviation 1.578 |
Other Pre-specified
GnRH Antagonist Evaluation
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.
Time frame: Week 2, Week 4, Week 12, Week 20, Week 24, Week 26, Week 36, Week 44, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Burning/Stinging | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Pain | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Any GnRH Antagonist Conditions Reported? | 15 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Flare or hot flashes | 4 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Injection site reactions | 11 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Burning/Stinging | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Pain | 9 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Bruising | 3 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Redness | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Difficulty in urination | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Injection site reactions | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Bone Pain | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Aggravation of weakness or other muscle symptoms | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | Onset of Allergic reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #1, Week 2 | No GnRH Antagonist conditions reported? | 15 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Any GnRH Antagonist Conditions Reported? | 4 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Flare or hot flashes | 2 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Injection site reactions | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Burning/Stinging | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Pain | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Bruising | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Redness | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Difficulty in urination | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Bone Pain | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Aggravation of weakness or other muscle symptoms | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | Onset of Allergic reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 2, Week 4 | No GnRH Antagonist conditions reported? | 53 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Any GnRH Antagonist Conditions Reported? | 5 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Flare or hot flashes | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Injection site reactions | 3 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Burning/Stinging | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Pain | 2 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Bruising | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Redness | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Difficulty in urination | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Bone Pain | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Aggravation of weakness or other muscle symptoms | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | Onset of Allergic reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 3, Week 12 | No GnRH Antagonist conditions reported? | 48 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Any GnRH Antagonist Conditions Reported? | 3 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Flare or hot flashes | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Injection site reactions | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Burning/Stinging | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Pain | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Bruising | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Redness | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Difficulty in urination | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Bone Pain | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Aggravation of weakness or other muscle symptoms | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | Onset of Allergic reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 4, Week 20 | No GnRH Antagonist conditions reported? | 53 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Any GnRH Antagonist Conditions Reported? | 3 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Flare or hot flashes | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Burning/Stinging | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Pain | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Bruising | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Redness | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Difficulty in urination | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Bone Pain | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Aggravation of weakness or other muscle symptoms | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | Onset of Allergic reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 5, Week 24 | No GnRH Antagonist conditions reported? | 55 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Any GnRH Antagonist Conditions Reported? | 16 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Flare or hot flashes | 2 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Injection site reactions | 15 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Burning/Stinging | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Pain | 15 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Bruising | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Redness | 3 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Difficulty in urination | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Bone Pain | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Aggravation of weakness or other muscle symptoms | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | Onset of Allergic reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Telephone Contact #2, Week 26 | No GnRH Antagonist conditions reported? | 6 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Any GnRH Antagonist Conditions Reported? | 3 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Flare or hot flashes | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Injection site reactions | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Bruising | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Redness | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Difficulty in urination | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Bone Pain | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Aggravation of weakness or other muscle symptoms | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | Onset of Allergic reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 6, Week 36 | No GnRH Antagonist conditions reported? | 51 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Any GnRH Antagonist Conditions Reported? | 3 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Flare or hot flashes | 2 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Injection site reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Burning/Stinging | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Pain | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Bruising | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Redness | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Difficulty in urination | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Bone Pain | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Aggravation of weakness or other muscle symptoms | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | Onset of Allergic reactions | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | Visit 7, Week 44 | No GnRH Antagonist conditions reported? | 53 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Any GnRH Antagonist Conditions Reported? | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Flare or hot flashes | 1 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Injection site reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Burning/Stinging | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Pain | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Bruising | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Redness | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Difficulty in urination | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Bone Pain | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Aggravation of weakness or other muscle symptoms | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | Onset of Allergic reactions | 0 Participants |
| Assigned Intervention | GnRH Antagonist Evaluation | End of Treatment, Week 48 | No GnRH Antagonist conditions reported? | 57 Participants |
Other Pre-specified
Height
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.
Time frame: Screening, Baseline, Week 4, Week 12, Week 20, Week 24, Week 36, Week 44, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Assigned Intervention | Height | Screening | 136.17 cm | Standard Deviation 8.292 |
| Assigned Intervention | Height | Baseline | 136.61 cm | Standard Deviation 8.071 |
| Assigned Intervention | Height | Visit 2, Week 4 | 137.32 cm | Standard Deviation 8.201 |
| Assigned Intervention | Height | Visit 3, Week 12 | 138.52 cm | Standard Deviation 8.284 |
| Assigned Intervention | Height | Visit 4, Week 20 | 138.87 cm | Standard Deviation 8.07 |
| Assigned Intervention | Height | Visit 5, Week 24 | 139.78 cm | Standard Deviation 8.206 |
| Assigned Intervention | Height | Visit 6, Week 36 | 140.99 cm | Standard Deviation 8.374 |
| Assigned Intervention | Height | Visit 7, Week 44 | 141.81 cm | Standard Deviation 8.268 |
| Assigned Intervention | Height | End of Treatment, Week 48 | 142.37 cm | Standard Deviation 8.207 |
Other Pre-specified
Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels.
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.
Time frame: Week 12, Week 24, Week 36, and Week 48
Population: Intent-to-Treat (ITT) population: Subjects providing consent/assent who received at least one dose of the study drug, fulfilled the protocol eligibility criteria, and provided at least one PD laboratory assessment post dosing.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 3, Week 12 : FSH | 37 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 3, Week 12 : Estradiol | 58 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 3, Week 12 : Oestradiol (HS) | 56 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 3, Week 12 : Testosterone | 2 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 5, Week 24 : FSH | 41 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 5, Week 24 : Estradiol | 59 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 5, Week 24 : Oestradiol (HS) | 58 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 5, Week 24 : Testosterone | 2 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 6, Week 36 : FSH | 26 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 6, Week 36 : Estradiol | 57 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 6, Week 36 : Oestradiol (HS) | 56 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | Visit 6, Week 36 : Testosterone | 2 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | End of Treatment, Week 48 : FSH | 32 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | End of Treatment, Week 48 : Estradiol | 56 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | End of Treatment, Week 48 : Oestradiol (HS) | 55 Participants |
| Assigned Intervention | Percentage of Subjects With Suppression of FSH, Estradiol, Oestradiol (HS), and Testosterone Measured by Blood Levels. | End of Treatment, Week 48 : Testosterone | 1 Participants |