Idiopathic Short Stature (ISS)
Conditions
Brief summary
The present randomized trial was initially intended to study the benefits of a combined treatment with growth hormone (GH) and a gonadotropin-releasing hormone (GnRH) agonist for pubertal children with idiopathic short stature. However, treatments were stopped in January 2012 at the request of the French drug agency. Therefore, a protocol amendment divided the study in two study periods. Study Period 1 involved combined treatment with somatropin and leuprorelin or treatment with somatropin alone. Participants from France who participated in this Period 1 of the study were asked to participate in a long term safety follow up defined as a Period 2 of the study. Participants from the Netherlands were offered participation in Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS, clinicaltrials.gov Identifier: NCT01088412) for long term safety follow up independent of this study.
Interventions
DRUGsomatropin
0.05 mg/kg/day
DRUGleuprorelin
11.25 mg/3 months
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 171 Months
Healthy volunteers
No
Inclusion criteria
* male or female children with ISS * age greater than or equal to 8 years and less than or equal to 12 years and 3 months for girls and greater than or equal to 9 years and less than or equal to 14 years and 3 months for boys * bone age less than or equal to 12.0 years for girls and less than or equal to 14.0 years for boys based on a central reading of an X-ray of the left hand and wrist * Pubertal stage B2 and B3 for girls based on the Tanner method * Pubertal stage G2 and G3 for boys based on the Tanner method
Exclusion criteria
* Growth hormone deficiency (GHD) * Insulin-like growth factor-I levels greater than 3 SDS * Chromosomal abnormality diagnosed locally on a karyotype. For girls, the karyotype to eliminate a Turner syndrome, is mandatory * Small for gestational age (SGA) * Has reached menarche (had her first menstrual period) * Have any significant concomitant disease that is likely to interfere with growth or with the study, or is a known contraindication to Growth Hormone treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Drug-related Adverse Events | Baseline through End of Study (up to 9 years) | A drug-related AE was an AE that occurred postdose or was present predose and became more severe postdose and was considered to be related to study treatment. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. |
| Adult Height Standard Deviation Score (SDS) | Baseline through End of Study (up to 9 years) | The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Adult Height SDS and Target Height SDS | Baseline through End of Study (up to 9 years) | This is the difference between the gender, age and country matched standard deviation score of adult height and standard deviation score of target height \[calculated as (mother's height (SDS) + father's height (SDS))/2\] for particular participant. The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. |
| Difference Between Adult Height SDS and Baseline Predicted Height SDS | Baseline through End up Study (up to 9 years) | This is the difference between the gender, age and country matched standard deviation score of adult height and standard deviation score of baseline predicted height \[calculated using the Bayley-Pinneau method based on height and bone age\] for particular participant. The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. |
| Height Velocity | Baseline through End of Study (up to 9 years) | Height velocity is the difference between 2 height measurements, divided by years elapsed between measurements. |
| Percentage of Children With Normal Adult Height SDS | Baseline through End of Study (up to 9 years) | Percentage of children with normal adult height SDS (greater than -2 SDS and less than +2 SDS) |
| Bone Age | Baseline through End of Study (up to 9 years) | Bone age measured using the X-Ray of left hand and wrist. |
| Difference Between Adult Height SDS and Baseline Height SDS | Baseline through End up Study (up to 9 years) | This is the difference between the gender, age and country matched standard deviation score of adult height and standard deviation score of baseline height for particular participant. The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. |
| Height SDS | Baseline through End of Study (up to 9 years) | SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. |
Countries
France, Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Somatropin and Leuprorelin 0.05mg/kg/day subcutaneous somatropin and 3-month formulation, subcutaneous or intramuscular injection of 11.25mg leuprorelin for three years (or for a minimum of 2 years until a chronological age of 13 years for girls and 15 years for boys, whichever occurs first). | 45 |
| Somatropin 0.05mg/kg/day subcutaneous somatropin only | 43 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Study Period 1 Treatment | Adverse Event | 1 | 1 |
| Study Period 1 Treatment | Lost to Follow-up | 3 | 0 |
| Study Period 1 Treatment | Other | 2 | 6 |
| Study Period 1 Treatment | Parent/Caregiver Decision | 1 | 2 |
| Study Period 1 Treatment | Physician Decision | 0 | 1 |
| Study Period 1 Treatment | Protocol Entry Criterion Not Met | 0 | 1 |
| Study Period 1 Treatment | Sponsor Decision | 34 | 32 |
| Study Period 1 Treatment | Withdrawal by Subject | 4 | 1 |
| Study Period 2 Long Term Follow-Up | Lost to Follow-up | 0 | 1 |
| Study Period 2 Long Term Follow-Up | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Somatropin and Leuprorelin | Total | Somatropin |
|---|---|---|---|
| Age, Continuous | 12.1 years STANDARD_DEVIATION 1.41 | 12.1 years STANDARD_DEVIATION 1.36 | 12.1 years STANDARD_DEVIATION 1.33 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 38 Participants | 78 Participants | 40 Participants |
| Region of Enrollment France | 39 participants | 77 participants | 38 participants |
| Region of Enrollment Netherlands | 6 participants | 11 participants | 5 participants |
| Sex: Female, Male Female | 26 Participants | 46 Participants | 20 Participants |
| Sex: Female, Male Male | 19 Participants | 42 Participants | 23 Participants |
| Standing Height | 131.6 centimeters STANDARD_DEVIATION 6.72 | 131.6 centimeters STANDARD_DEVIATION 6.24 | 131.6 centimeters STANDARD_DEVIATION 5.78 |
| Standing Height SDS | -2.5 Standard Deviation Score STANDARD_DEVIATION 0.45 | -2.5 Standard Deviation Score STANDARD_DEVIATION 0.045 | -2.5 Standard Deviation Score STANDARD_DEVIATION 0.46 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 46 | 36 / 45 |
| serious Total, serious adverse events | 12 / 46 | 7 / 45 |
Outcome results
Primary
Adult Height Standard Deviation Score (SDS)
The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height.
Time frame: Baseline through End of Study (up to 9 years)
Population: All participants who received at least one dose of study drug with at least one follow up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Somatropin and Leuprorelin | Adult Height Standard Deviation Score (SDS) | -1.8 standard deviation score | Standard Deviation 0.53 |
| Somatropin | Adult Height Standard Deviation Score (SDS) | -1.9 standard deviation score | Standard Deviation 0.77 |
Primary
Number of Participants With One or More Drug-related Adverse Events
A drug-related AE was an AE that occurred postdose or was present predose and became more severe postdose and was considered to be related to study treatment. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline through End of Study (up to 9 years)
Population: All participants who received at least one dose of study drug in Period 1 and all participants who entered Period 2 (safety population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Somatropin and Leuprorelin | Number of Participants With One or More Drug-related Adverse Events | Study Period 1 (n=46, 45) | 42 participants |
| Somatropin and Leuprorelin | Number of Participants With One or More Drug-related Adverse Events | Study Period 2 (n=20, 19) | 11 participants |
| Somatropin | Number of Participants With One or More Drug-related Adverse Events | Study Period 1 (n=46, 45) | 38 participants |
| Somatropin | Number of Participants With One or More Drug-related Adverse Events | Study Period 2 (n=20, 19) | 9 participants |
Secondary
Bone Age
Bone age measured using the X-Ray of left hand and wrist.
Time frame: Baseline through End of Study (up to 9 years)
Population: All participants who received at least one dose of study drug with at least one follow up visit. The safety follow up participants did not reach final height at end of Period 1 unless final height is noted for participants that reached final height at the end of Period 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin and Leuprorelin | Bone Age | Month 12 (n=40, 41) | 11.7 years | Standard Deviation 1.59 |
| Somatropin and Leuprorelin | Bone Age | Safety follow up 6 months (n=16, 7) | 14.1 years | Standard Deviation 1.11 |
| Somatropin and Leuprorelin | Bone Age | Month 36 (n=18, 18) | 13.3 years | Standard Deviation 1.49 |
| Somatropin and Leuprorelin | Bone Age | Safety follow up 18 months (n=12, 3) | 15.2 years | Standard Deviation 1.25 |
| Somatropin and Leuprorelin | Bone Age | Month 24 (n=34, 37) | 12.4 years | Standard Deviation 1.32 |
| Somatropin and Leuprorelin | Bone Age | Safety follow up 36 months (n=5, 0) | 15.7 years | Standard Deviation 1.04 |
| Somatropin and Leuprorelin | Bone Age | Month 48 (n=7, 8) | 14.8 years | Standard Deviation 1.33 |
| Somatropin and Leuprorelin | Bone Age | Safety follow up 12 months (final height)(n=18,14) | 19.6 years | Standard Deviation 14.53 |
| Somatropin and Leuprorelin | Bone Age | Randomization (n=45, 43) | 10.8 years | Standard Deviation 1.58 |
| Somatropin | Bone Age | Safety follow up 12 months (final height)(n=18,14) | 16.3 years | Standard Deviation 1.27 |
| Somatropin | Bone Age | Randomization (n=45, 43) | 11.0 years | Standard Deviation 1.45 |
| Somatropin | Bone Age | Month 12 (n=40, 41) | 12.1 years | Standard Deviation 1.12 |
| Somatropin | Bone Age | Month 24 (n=34, 37) | 13.4 years | Standard Deviation 1.09 |
| Somatropin | Bone Age | Month 36 (n=18, 18) | 14.5 years | Standard Deviation 1.64 |
| Somatropin | Bone Age | Month 48 (n=7, 8) | 15.4 years | Standard Deviation 1.27 |
| Somatropin | Bone Age | Safety follow up 6 months (n=16, 7) | 14.9 years | Standard Deviation 0.81 |
| Somatropin | Bone Age | Safety follow up 18 months (n=12, 3) | 17.0 years | Standard Deviation 1 |
| Somatropin | Bone Age | Safety follow up 36 months (n=5, 0) | 0 years | Standard Deviation 0 |
Secondary
Difference Between Adult Height SDS and Baseline Height SDS
This is the difference between the gender, age and country matched standard deviation score of adult height and standard deviation score of baseline height for particular participant. The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height.
Time frame: Baseline through End up Study (up to 9 years)
Population: All participants who received who reached final height.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Somatropin and Leuprorelin | Difference Between Adult Height SDS and Baseline Height SDS | 0.6 standard deviation score | Standard Deviation 0.59 |
| Somatropin | Difference Between Adult Height SDS and Baseline Height SDS | 0.6 standard deviation score | Standard Deviation 0.67 |
Secondary
Difference Between Adult Height SDS and Baseline Predicted Height SDS
This is the difference between the gender, age and country matched standard deviation score of adult height and standard deviation score of baseline predicted height \[calculated using the Bayley-Pinneau method based on height and bone age\] for particular participant. The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height.
Time frame: Baseline through End up Study (up to 9 years)
Population: All participants who received who reached final height.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Somatropin and Leuprorelin | Difference Between Adult Height SDS and Baseline Predicted Height SDS | 1.1 standard deviation score | Standard Deviation 0.96 |
| Somatropin | Difference Between Adult Height SDS and Baseline Predicted Height SDS | 1.2 standard deviation score | Standard Deviation 0.7 |
Secondary
Difference Between Adult Height SDS and Target Height SDS
This is the difference between the gender, age and country matched standard deviation score of adult height and standard deviation score of target height \[calculated as (mother's height (SDS) + father's height (SDS))/2\] for particular participant. The height of the participants were measured barefoot using a standard wall-mounted Harpenden stadiometer. SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height.
Time frame: Baseline through End of Study (up to 9 years)
Population: All participants who received who reached final height.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Somatropin and Leuprorelin | Difference Between Adult Height SDS and Target Height SDS | -0.6 standard deviation score | Standard Deviation 0.89 |
| Somatropin | Difference Between Adult Height SDS and Target Height SDS | -1.2 standard deviation score | Standard Deviation 0.8 |
Secondary
Height SDS
SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height.
Time frame: Baseline through End of Study (up to 9 years)
Population: All participants who received at least one dose of study drug with at least one follow up visit. The safety follow up participants did not reach final height at end of Period 1 unless final height is noted for participants that reached final height at the end of Period 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin and Leuprorelin | Height SDS | Safety follow up 24 months (n=9, 1) | -1.9 standard deviation score | Standard Deviation 0.46 |
| Somatropin and Leuprorelin | Height SDS | Month 3 (n=45, 43) | -2.4 standard deviation score | Standard Deviation 0.42 |
| Somatropin and Leuprorelin | Height SDS | Month 6 (n=45, 42) | -2.3 standard deviation score | Standard Deviation 0.48 |
| Somatropin and Leuprorelin | Height SDS | Month 12 (n=44, 42) | -2.2 standard deviation score | Standard Deviation 0.5 |
| Somatropin and Leuprorelin | Height SDS | Month 18 (n=42, 42) | -2.2 standard deviation score | Standard Deviation 0.53 |
| Somatropin and Leuprorelin | Height SDS | Month 24 (n=37, 41) | -2.3 standard deviation score | Standard Deviation 0.58 |
| Somatropin and Leuprorelin | Height SDS | Month 36 (n=18, 19) | -2.0 standard deviation score | Standard Deviation 0.65 |
| Somatropin and Leuprorelin | Height SDS | Month 42 (n=13, 14) | -1.8 standard deviation score | Standard Deviation 0.68 |
| Somatropin and Leuprorelin | Height SDS | Month 48 (n=7, 8) | -1.6 standard deviation score | Standard Deviation 0.52 |
| Somatropin and Leuprorelin | Height SDS | Month 54 (n=1, 1) | -1.0 standard deviation score | Standard Deviation 0 |
| Somatropin and Leuprorelin | Height SDS | Safety follow up 6 months (n=16, 9) | -2.1 standard deviation score | Standard Deviation 0.65 |
| Somatropin and Leuprorelin | Height SDS | Safety follow up 12 months(n=15, 8) | -1.9 standard deviation score | Standard Deviation 0.55 |
| Somatropin and Leuprorelin | Height SDS | Safety follow up 18 months (n=12, 4) | -1.9 standard deviation score | Standard Deviation 0.63 |
| Somatropin and Leuprorelin | Height SDS | Safety follow up 36 months (n=5, 0) | -1.9 standard deviation score | Standard Deviation 0.67 |
| Somatropin and Leuprorelin | Height SDS | Safety follow up 42 months (n=2, 0) | -2.4 standard deviation score | Standard Deviation 0.18 |
| Somatropin and Leuprorelin | Height SDS | Safety follow up 12 months (final height)(n=18,14) | -1.9 standard deviation score | Standard Deviation 0.46 |
| Somatropin and Leuprorelin | Height SDS | Safety follow up 24 months (final height) (n=7,10) | -1.6 standard deviation score | Standard Deviation 0.56 |
| Somatropin and Leuprorelin | Height SDS | Safety follow up 36 months (final height) (n=3,7) | -1.2 standard deviation score | Standard Deviation 0.9 |
| Somatropin and Leuprorelin | Height SDS | Month 30 (n=25, 25) | -2.2 standard deviation score | Standard Deviation 0.63 |
| Somatropin and Leuprorelin | Height SDS | Randomization (n=45, 43) | -2.5 standard deviation score | Standard Deviation 0.45 |
| Somatropin | Height SDS | Safety follow up 42 months (n=2, 0) | 0 standard deviation score | Standard Deviation 0 |
| Somatropin | Height SDS | Randomization (n=45, 43) | -2.5 standard deviation score | Standard Deviation 0.46 |
| Somatropin | Height SDS | Safety follow up 6 months (n=16, 9) | -1.7 standard deviation score | Standard Deviation 0.77 |
| Somatropin | Height SDS | Month 3 (n=45, 43) | -2.4 standard deviation score | Standard Deviation 0.47 |
| Somatropin | Height SDS | Month 48 (n=7, 8) | -1.9 standard deviation score | Standard Deviation 0.65 |
| Somatropin | Height SDS | Month 6 (n=45, 42) | -2.2 standard deviation score | Standard Deviation 0.52 |
| Somatropin | Height SDS | Safety follow up 12 months(n=15, 8) | -1.7 standard deviation score | Standard Deviation 0.77 |
| Somatropin | Height SDS | Month 12 (n=44, 42) | -2.0 standard deviation score | Standard Deviation 0.57 |
| Somatropin | Height SDS | Safety follow up 12 months (final height)(n=18,14) | -1.8 standard deviation score | Standard Deviation 0.71 |
| Somatropin | Height SDS | Month 18 (n=42, 42) | -1.9 standard deviation score | Standard Deviation 0.63 |
| Somatropin | Height SDS | Safety follow up 18 months (n=12, 4) | -1.9 standard deviation score | Standard Deviation 0.78 |
| Somatropin | Height SDS | Month 24 (n=37, 41) | -1.8 standard deviation score | Standard Deviation 0.67 |
| Somatropin | Height SDS | Month 30 (n=25, 25) | -2.0 standard deviation score | Standard Deviation 0.58 |
| Somatropin | Height SDS | Safety follow up 24 months (n=9, 1) | -1.2 standard deviation score | Standard Deviation 0 |
| Somatropin | Height SDS | Month 36 (n=18, 19) | -2.0 standard deviation score | Standard Deviation 0.68 |
| Somatropin | Height SDS | Safety follow up 36 months (final height) (n=3,7) | -2.2 standard deviation score | Standard Deviation 0.94 |
| Somatropin | Height SDS | Month 42 (n=13, 14) | -1.9 standard deviation score | Standard Deviation 0.66 |
| Somatropin | Height SDS | Safety follow up 36 months (n=5, 0) | 0 standard deviation score | Standard Deviation 0 |
| Somatropin | Height SDS | Safety follow up 24 months (final height) (n=7,10) | -2.0 standard deviation score | Standard Deviation 0.79 |
| Somatropin | Height SDS | Month 54 (n=1, 1) | -1.7 standard deviation score | Standard Deviation 0 |
Secondary
Height Velocity
Height velocity is the difference between 2 height measurements, divided by years elapsed between measurements.
Time frame: Baseline through End of Study (up to 9 years)
Population: All participants who received at least one dose of study drug with at least one follow up visit. The safety follow up participants did not reach final height at end of Period 1 unless final height is noted for participants that reached final height at the end of Period 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Somatropin and Leuprorelin | Height Velocity | Randomization (n=45, 43) | 7.8 centimeter per year | Standard Deviation 6.92 |
| Somatropin and Leuprorelin | Height Velocity | Month 3 (n=45, 43) | 9.9 centimeter per year | Standard Deviation 3.94 |
| Somatropin and Leuprorelin | Height Velocity | Month 6 (n=45, 42) | 8.1 centimeter per year | Standard Deviation 2.31 |
| Somatropin and Leuprorelin | Height Velocity | Month 12 (n=44, 42) | 7.0 centimeter per year | Standard Deviation 1.64 |
| Somatropin and Leuprorelin | Height Velocity | Month 18 (n=42, 42) | 6.6 centimeter per year | Standard Deviation 1.68 |
| Somatropin and Leuprorelin | Height Velocity | Month 24 (n=37, 41) | 4.9 centimeter per year | Standard Deviation 1.33 |
| Somatropin and Leuprorelin | Height Velocity | Month 30 (n=25, 25) | 6.2 centimeter per year | Standard Deviation 2.09 |
| Somatropin and Leuprorelin | Height Velocity | Safety follow up 36 months (final height) (n=3,7) | 0.9 centimeter per year | Standard Deviation 0.78 |
| Somatropin and Leuprorelin | Height Velocity | Month 36 (n=18, 19) | 6.6 centimeter per year | Standard Deviation 3.25 |
| Somatropin and Leuprorelin | Height Velocity | Month 42 (n=13, 14) | 5.7 centimeter per year | Standard Deviation 1.94 |
| Somatropin and Leuprorelin | Height Velocity | Month 48 (n=7, 8) | 5.4 centimeter per year | Standard Deviation 2.27 |
| Somatropin and Leuprorelin | Height Velocity | Month 54 (n=1, 1) | 6.3 centimeter per year | Standard Deviation 0 |
| Somatropin and Leuprorelin | Height Velocity | Safety follow up 6 months (n=16, 9) | 4.6 centimeter per year | Standard Deviation 2.08 |
| Somatropin and Leuprorelin | Height Velocity | Safety follow up 12 months(n=15, 8) | 2.9 centimeter per year | Standard Deviation 2.37 |
| Somatropin and Leuprorelin | Height Velocity | Safety follow up 18 months (n=12, 4) | 3.3 centimeter per year | Standard Deviation 1.69 |
| Somatropin and Leuprorelin | Height Velocity | Safety follow up 24 months (n=9, 1) | 2.0 centimeter per year | Standard Deviation 1.32 |
| Somatropin and Leuprorelin | Height Velocity | Safety follow up 36 months (n=5, 0) | 1.3 centimeter per year | Standard Deviation 0.53 |
| Somatropin and Leuprorelin | Height Velocity | Safety follow up 42 months (n=2, 0) | 2.1 centimeter per year | Standard Deviation 2.45 |
| Somatropin and Leuprorelin | Height Velocity | Safety follow up 12 months (final height)(n=18,14) | 0.5 centimeter per year | Standard Deviation 0.86 |
| Somatropin and Leuprorelin | Height Velocity | Safety follow up 24 months (final height) (n=7,10) | 0.3 centimeter per year | Standard Deviation 0.77 |
| Somatropin | Height Velocity | Month 42 (n=13, 14) | 3.7 centimeter per year | Standard Deviation 2.17 |
| Somatropin | Height Velocity | Randomization (n=45, 43) | 7.4 centimeter per year | Standard Deviation 6.03 |
| Somatropin | Height Velocity | Safety follow up 18 months (n=12, 4) | 1.2 centimeter per year | Standard Deviation 1.2 |
| Somatropin | Height Velocity | Month 3 (n=45, 43) | 10.6 centimeter per year | Standard Deviation 3.53 |
| Somatropin | Height Velocity | Month 48 (n=7, 8) | 2.9 centimeter per year | Standard Deviation 2.73 |
| Somatropin | Height Velocity | Month 6 (n=45, 42) | 9.7 centimeter per year | Standard Deviation 2.8 |
| Somatropin | Height Velocity | Safety follow up 12 months (final height)(n=18,14) | 0.8 centimeter per year | Standard Deviation 1.59 |
| Somatropin | Height Velocity | Month 12 (n=44, 42) | 8.8 centimeter per year | Standard Deviation 2.33 |
| Somatropin | Height Velocity | Month 54 (n=1, 1) | 7.1 centimeter per year | Standard Deviation 0 |
| Somatropin | Height Velocity | Month 18 (n=42, 42) | 8.4 centimeter per year | Standard Deviation 2.64 |
| Somatropin | Height Velocity | Safety follow up 24 months (n=9, 1) | 2.5 centimeter per year | Standard Deviation 0 |
| Somatropin | Height Velocity | Month 24 (n=37, 41) | 7.8 centimeter per year | Standard Deviation 3.36 |
| Somatropin | Height Velocity | Safety follow up 6 months (n=16, 9) | 4.5 centimeter per year | Standard Deviation 2.45 |
| Somatropin | Height Velocity | Safety follow up 24 months (final height) (n=7,10) | 0.3 centimeter per year | Standard Deviation 0.97 |
| Somatropin | Height Velocity | Safety follow up 42 months (n=2, 0) | 0 centimeter per year | Standard Deviation 0 |
| Somatropin | Height Velocity | Safety follow up 36 months (final height) (n=3,7) | 0.3 centimeter per year | Standard Deviation 0.6 |
| Somatropin | Height Velocity | Month 30 (n=25, 25) | 5.8 centimeter per year | Standard Deviation 2.93 |
| Somatropin | Height Velocity | Safety follow up 12 months(n=15, 8) | 2.3 centimeter per year | Standard Deviation 1.43 |
| Somatropin | Height Velocity | Month 36 (n=18, 19) | 3.5 centimeter per year | Standard Deviation 2.71 |
| Somatropin | Height Velocity | Safety follow up 36 months (n=5, 0) | 0 centimeter per year | Standard Deviation 0 |
Secondary
Percentage of Children With Normal Adult Height SDS
Percentage of children with normal adult height SDS (greater than -2 SDS and less than +2 SDS)
Time frame: Baseline through End of Study (up to 9 years)
Population: All participants who received at least one dose of study drug with at least one follow up visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Somatropin and Leuprorelin | Percentage of Children With Normal Adult Height SDS | 26.7 percentage of participants |
| Somatropin | Percentage of Children With Normal Adult Height SDS | 25.6 percentage of participants |