Insulin-like Growth Factor-1 Deficiency
Conditions
Keywords
IGF-1 Deficiency, growth, ISS, Constitutional growth delay, Primary IGFD, Primary IGF Deficiency
Brief summary
IGF-1 (insulin-like growth factor-1) is a hormone that is normally produced in the body in response to another hormone called growth hormone. Growth Hormone is produced by a small gland at the base of the brain (the pituitary). Together IGF-1 and GH are large contributors to growth during infancy, childhood, and adolescence. Children with IGF Deficiency are short and have an imbalance in the levels of growth hormone and IGF-1 that their body produces. Their growth hormone levels are normal or even high, but IGF-1 levels do not increase normally in response to growth hormone. As a result, they have a type of growth hormone insensitivity and an inability to grow normally. This study is a test to see whether daily dosing with a combination of rhIGF-1 and rhGH will help children with IGFD grow taller more quickly than children treated with rhGH alone. The study medications, rhIGF-1 and rhGH, are approved by the US Food and Drug Administration (FDA) for use in some growth disorders in children, but the combination of rhIGF-1 and rhGH in children with IGF-1 deficiency (IGFD) is investigational.
Interventions
DRUGNutropinAq® (Somatropin [rDNA origin])
rhGH (Somatropin) 45µg/kg once daily injection
DRUGIncrelex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Parents or legally authorized representatives must give signed informed consent before any trial-related activities * IGF-1 SDS of ≤ -1 for age and gender * Short stature, as defined by a height SDS of ≤ -2 for age and gender * Chronological age ≥ 5 years * Bone age ≤ 11 years in boys and ≤ 9 years in girls * GH sufficiency, defined as a maximal stimulated GH response of greater than or equal to 10 ng/mL at Visit 2 (note: upon approval of the Medical Monitor, the result of a prior GH stimulation test may satisfy this requirement). * Prepubertal status * Adequate nutrition as evidenced by a body mass index (BMI) greater than or equal to the 5th percentile for age and gender
Exclusion criteria
* Severe Primary IGFD (defined as height and IGF-1 SDS ≤ 3, and stimulated GH response greater than or equal to 10 ng/mL) * Prior or current use of medications with the potential to alter growth patterns including GH, IGF-1, IGFBP-3, gonadotrophin agonists (e.g., Lupron), aromatase inhibitors, androgens and estrogens * Known or suspected allergy to rhGH, rhIGF-1 or a constituent of their formulations * Current use of medications for attention deficit disorder * A chronic health condition that requires anti-inflammatory steroids or daily medication unless approved by the Medical Monitor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Height Velocity | First year of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Change in Height Standard Deviation Score (SDS) | First, second, third and fourth year | Height was measured standing and without shoes, and recorded as the mean of three measurements (the subject being repositioned each time) by the same observer using a Harpenden or other wall-mounted stadiometer which was to be calibrated prior to measurement of each subject and a calibration log kept. The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002) |
| Predicted Adult Height (PAH) | At baseline (Day 1), year 1,2,3 and 4 | Predicted Adult Height calculated by method, Roche-Wainer-Thissen (RWT) and mid-parental target height SDS. The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002) |
| Total Change From Baseline (Day 1) in BMI SDS | At year 1,2,3,4 and end of study (visit 23) versus baseline (day 1) | BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002) |
| Skeletal Maturation | At baseline(day 1), year 1,2,3 and 4 | Assessed by bone age. Bone age was determined by the radiograph. The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002) |
| Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | At Baseline (Day 1), Year 1,2,3 and 4 | — |
| Height Velocity | Second, third and fourth year | — |
| Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | At Baseline (Day 1), Year 1,2,3 and 4 | — |
| Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | At Baseline (Day 1), Year 1,2,3 and 4 | — |
| Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | At Baseline (Day 1), Year 1,2,3 and 4 | — |
| Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | At Baseline (Day 1), Year 1,2,3 and 4 | — |
| Summary of Adverse Events With Number of Occurrences | Approximately up to 4 years. | A Data Monitoring Committee (DMC) was established to monitor subject safety |
| Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | At Baseline (Day 1), Year 1,2,3 and 4 | — |
Countries
United States
Participant flow
Recruitment details
Date of first enrolment: December 2007. Date of last completed: March 2012. This was a Phase II, multicenter, randomized, open-label, parallel-group, active treatment controlled, dose selection study conducted at 27 centers in the US.
Pre-assignment details
Study screened 155 subjects. Due to failure in screening 49 subjects were excluded from the trial before assignment to groups.
Participants by arm
| Arm | Count |
|---|---|
| 45 rhGH Alone Nutropin AQ® (Somatropin \[rDNA origin\]): rhGH (Somatropin) 45µg/kg once daily injection | 26 |
| 45 rhGH + 50 rhIGF-1 Increlex® (Mecasermin \[rDNA origin\] injection) + Nutropin AQ® (Somatropin \[rDNA origin\]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections | 27 |
| 45 rhGH + 100 rhIGF-1 Increlex® (Mecasermin \[rDNA origin\] injection) + Nutropin AQ® (Somatropin \[rDNA origin\]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections | 27 |
| 45 rhGH + 150 rhIGF-1 Increlex® (Mecasermin \[rDNA origin\] injection) + Nutropin AQ® (Somatropin \[rDNA origin\]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection | 26 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 5 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 | 0 |
| Overall Study | Patient/Parent Decision | 1 | 6 | 4 | 3 |
| Overall Study | Protocol Violation | 1 | 2 | 0 | 2 |
| Overall Study | Sponsor Decision | 20 | 16 | 17 | 19 |
Baseline characteristics
| Characteristic | 45 rhGH + 50 rhIGF-1 | 45 rhGH Alone | Total | 45 rhGH + 150 rhIGF-1 | 45 rhGH + 100 rhIGF-1 |
|---|---|---|---|---|---|
| Age, Continuous | 8.4 years STANDARD_DEVIATION 2 | 9.2 years STANDARD_DEVIATION 2 | 8.8 years STANDARD_DEVIATION 2.1 | 8.8 years STANDARD_DEVIATION 2.3 | 9.0 years STANDARD_DEVIATION 2.2 |
| Body Mass Index (BMI) | -0.5 SDS STANDARD_DEVIATION 0.7 | -0.3 SDS STANDARD_DEVIATION 0.7 | -0.4 SDS STANDARD_DEVIATION 0.7 | -0.5 SDS STANDARD_DEVIATION 0.8 | -0.4 SDS STANDARD_DEVIATION 0.7 |
| Bone age imputed | 7.2 years STANDARD_DEVIATION 1.8 | 7.6 years STANDARD_DEVIATION 1.7 | 7.3 years STANDARD_DEVIATION 1.9 | 7.3 years STANDARD_DEVIATION 2 | 7.2 years STANDARD_DEVIATION 2 |
| Father height | 169 cm STANDARD_DEVIATION 5 | 172 cm STANDARD_DEVIATION 4 | 172 cm STANDARD_DEVIATION 6 | 172 cm STANDARD_DEVIATION 6 | 173 cm STANDARD_DEVIATION 7 |
| Height | -2.5 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.4 | -2.5 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.5 | -2.5 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.4 | -2.6 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.4 | -2.6 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.4 |
| Height Age | 6.0 years STANDARD_DEVIATION 1.5 | 6.5 years STANDARD_DEVIATION 1.6 | 6.3 years STANDARD_DEVIATION 1.7 | 6.2 years STANDARD_DEVIATION 1.9 | 6.4 years STANDARD_DEVIATION 1.8 |
| IGF-1 | -2.0 SDS STANDARD_DEVIATION 0.7 | -1.8 SDS STANDARD_DEVIATION 0.5 | -1.9 SDS STANDARD_DEVIATION 0.6 | -2.0 SDS STANDARD_DEVIATION 0.6 | -1.8 SDS STANDARD_DEVIATION 0.6 |
| IGFBP-3 SDS | -1.2 SDS STANDARD_DEVIATION 0.9 | -1.1 SDS STANDARD_DEVIATION 0.7 | -1.1 SDS STANDARD_DEVIATION 0.8 | -1.3 SDS STANDARD_DEVIATION 0.8 | -1.0 SDS STANDARD_DEVIATION 0.8 |
| Max stimulated GH | 18.2 ng/mL STANDARD_DEVIATION 8.4 | 17.9 ng/mL STANDARD_DEVIATION 8.9 | 18.9 ng/mL STANDARD_DEVIATION 8 | 20.1 ng/mL STANDARD_DEVIATION 8.4 | 19.5 ng/mL STANDARD_DEVIATION 6.3 |
| Mid-Parental target height | -0.6 SDS STANDARD_DEVIATION 0.5 | -0.5 SDS STANDARD_DEVIATION 0.4 | -0.5 SDS STANDARD_DEVIATION 0.5 | -0.5 SDS STANDARD_DEVIATION 0.5 | -0.5 SDS STANDARD_DEVIATION 0.5 |
| Mother height | 157 cm STANDARD_DEVIATION 5 | 157 cm STANDARD_DEVIATION 5 | 158 cm STANDARD_DEVIATION 6 | 159 cm STANDARD_DEVIATION 7 | 157 cm STANDARD_DEVIATION 6 |
| Race Asian | 4 participants | 2 participants | 8 participants | 1 participants | 1 participants |
| Race Black | 1 participants | 1 participants | 3 participants | 0 participants | 1 participants |
| Race Hawaiian or Pacific Islander/ White | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants |
| Race Hispanic | 1 participants | 4 participants | 10 participants | 2 participants | 3 participants |
| Race Hispanic/White | 1 participants | 1 participants | 5 participants | 0 participants | 3 participants |
| Race White | 20 participants | 17 participants | 79 participants | 23 participants | 19 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 21 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 22 Participants | 21 Participants | 85 Participants | 22 Participants | 20 Participants |
| Weight | -2.1 SDS STANDARD_DEVIATION 0.6 | -2.0 SDS STANDARD_DEVIATION 0.7 | -2.1 SDS STANDARD_DEVIATION 0.7 | -2.2 SDS STANDARD_DEVIATION 0.9 | -2.0 SDS STANDARD_DEVIATION 0.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 26 | 27 / 27 | 27 / 27 | 26 / 26 |
| serious Total, serious adverse events | 1 / 26 | 1 / 27 | 2 / 27 | 1 / 26 |
Outcome results
Primary
Height Velocity
Time frame: First year of treatment
Population: Modified Intent-To-Treat (MITT): MITT population comprised all subjects who were randomized and had at least one post-baseline height measurement.~\[n= 25,27,27,26\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhGH Alone | Height Velocity | 9.3 cm/y | Standard Deviation 1.7 |
| 45 rhGH + 50 rhIGF-1 | Height Velocity | 10.1 cm/y | Standard Deviation 1.3 |
| 45 rhGH + 100 rhIGF-1 | Height Velocity | 9.7 cm/y | Standard Deviation 2.5 |
| 45 rhGH + 150 rhIGF-1 | Height Velocity | 11.2 cm/y | Standard Deviation 2.1 |
Secondary
Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Population: Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 1 (Trough) [n=24,24,21,24] | 16.0 mg/L | Standard Deviation 4 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 4 (Trough) [n= 3,5,5,3] | 13.7 mg/L | Standard Deviation 1.5 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 2 (Trough) [n= 22,21,19,20] | 15.2 mg/L | Standard Deviation 4.3 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 3 (Trough) [n= 21,18,18,19] | 13.7 mg/L | Standard Deviation 2.3 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Day 1 (Baseline) [n=25,26,26,25] | 10.6 mg/L | Standard Deviation 3 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 2 (Trough) [n= 22,21,19,20] | 14.3 mg/L | Standard Deviation 5.2 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Day 1 (Baseline) [n=25,26,26,25] | 10.0 mg/L | Standard Deviation 3.4 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 1 (Trough) [n=24,24,21,24] | 12.7 mg/L | Standard Deviation 2.3 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 3 (Trough) [n= 21,18,18,19] | 13.0 mg/L | Standard Deviation 3.2 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 4 (Trough) [n= 3,5,5,3] | 12.0 mg/L | Standard Deviation 2.2 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 3 (Trough) [n= 21,18,18,19] | 12.9 mg/L | Standard Deviation 2.7 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 2 (Trough) [n= 22,21,19,20] | 15.7 mg/L | Standard Deviation 4 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 4 (Trough) [n= 3,5,5,3] | 12.0 mg/L | Standard Deviation 3 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Day 1 (Baseline) [n=25,26,26,25] | 10.9 mg/L | Standard Deviation 3 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 1 (Trough) [n=24,24,21,24] | 14.0 mg/L | Standard Deviation 3.9 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 3 (Trough) [n= 21,18,18,19] | 11.2 mg/L | Standard Deviation 4 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 1 (Trough) [n=24,24,21,24] | 11.5 mg/L | Standard Deviation 2.8 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 2 (Trough) [n= 22,21,19,20] | 13.7 mg/L | Standard Deviation 4.5 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Day 1 (Baseline) [n=25,26,26,25] | 11.0 mg/L | Standard Deviation 4.1 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS) | Year 4 (Trough) [n= 3,5,5,3] | 13.7 mg/L | Standard Deviation 2.1 |
Secondary
Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Population: Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 3 (Trough) [n= 21,17,17,19] | 672.0 pmol/L | Standard Deviation 224.4 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 1 (Trough) [n= 23,24,20,24] | 729.4 pmol/L | Standard Deviation 229.5 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 4 (Trough) [n= 3,5,5,3] | 714.0 pmol/L | Standard Deviation 38.5 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 2 (Trough) [n=22,21,18,21] | 725.6 pmol/L | Standard Deviation 308.4 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Day 1 (Baseline) [n= 25,26,25,25] | 785.8 pmol/L | Standard Deviation 291.1 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 2 (Trough) [n=22,21,18,21] | 589.3 pmol/L | Standard Deviation 171.6 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 3 (Trough) [n= 21,17,17,19] | 646.9 pmol/L | Standard Deviation 204.1 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 4 (Trough) [n= 3,5,5,3] | 516.9 pmol/L | Standard Deviation 252.5 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 1 (Trough) [n= 23,24,20,24] | 576.9 pmol/L | Standard Deviation 211 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Day 1 (Baseline) [n= 25,26,25,25] | 735.8 pmol/L | Standard Deviation 343.5 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 2 (Trough) [n=22,21,18,21] | 562.5 pmol/L | Standard Deviation 184.4 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Day 1 (Baseline) [n= 25,26,25,25] | 698.8 pmol/L | Standard Deviation 212.2 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 1 (Trough) [n= 23,24,20,24] | 598.9 pmol/L | Standard Deviation 187.3 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 3 (Trough) [n= 21,17,17,19] | 614.3 pmol/L | Standard Deviation 210.9 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 4 (Trough) [n= 3,5,5,3] | 798.2 pmol/L | Standard Deviation 336.1 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 3 (Trough) [n= 21,17,17,19] | 554.9 pmol/L | Standard Deviation 197 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 1 (Trough) [n= 23,24,20,24] | 530.5 pmol/L | Standard Deviation 233.5 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Day 1 (Baseline) [n= 25,26,25,25] | 719.0 pmol/L | Standard Deviation 261.5 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 2 (Trough) [n=22,21,18,21] | 564.6 pmol/L | Standard Deviation 171.9 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP) | Year 4 (Trough) [n= 3,5,5,3] | 519.7 pmol/L | Standard Deviation 141.1 |
Secondary
Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Population: Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 3 (Trough) [n=20,18,15,20] | 2.8 ng/mL | Standard Deviation 5.1 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 1 (Trough) [n=23,25,18,25] | 1.7 ng/mL | Standard Deviation 2.1 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 4 (Trough) [n=3,5,4,3] | 1.2 ng/mL | Standard Deviation 0.3 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 2 (Trough) [n=21,20,16,20] | 4.0 ng/mL | Standard Deviation 6 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Day 1 (Baseline) [n=23,25,18,25] | 1.1 ng/mL | Standard Deviation 2.2 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 2 (Trough) [n=21,20,16,20] | 2.2 ng/mL | Standard Deviation 4.2 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 3 (Trough) [n=20,18,15,20] | 1.3 ng/mL | Standard Deviation 1.6 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 4 (Trough) [n=3,5,4,3] | 0.5 ng/mL | Standard Deviation 0.4 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 1 (Trough) [n=23,25,18,25] | 3.5 ng/mL | Standard Deviation 12.9 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Day 1 (Baseline) [n=23,25,18,25] | 2.9 ng/mL | Standard Deviation 8.1 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 2 (Trough) [n=21,20,16,20] | 2.7 ng/mL | Standard Deviation 3.9 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Day 1 (Baseline) [n=23,25,18,25] | 2.4 ng/mL | Standard Deviation 4.5 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 1 (Trough) [n=23,25,18,25] | 2.1 ng/mL | Standard Deviation 3.2 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 3 (Trough) [n=20,18,15,20] | 1.5 ng/mL | Standard Deviation 1.4 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 4 (Trough) [n=3,5,4,3] | 3.0 ng/mL | Standard Deviation 2.9 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 3 (Trough) [n=20,18,15,20] | 1.9 ng/mL | Standard Deviation 3.5 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 1 (Trough) [n=23,25,18,25] | 1.4 ng/mL | Standard Deviation 2.1 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Day 1 (Baseline) [n=23,25,18,25] | 1.9 ng/mL | Standard Deviation 2.3 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 2 (Trough) [n=21,20,16,20] | 1.4 ng/mL | Standard Deviation 1.2 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH) | Year 4 (Trough) [n=3,5,4,3] | 1.1 ng/mL | Standard Deviation 0.6 |
Secondary
Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Population: Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 3 (Trough)[n= 21,19,19, 20] | 335.3 ng/mL | Standard Deviation 110 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 1 (Trough) [n= 24,25,22,25] | 278.2 ng/mL | Standard Deviation 95.5 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 4 (Trough)[n= 3,5,5,3] | 347.7 ng/mL | Standard Deviation 130.7 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 2 (Trough) [n= 22,21,20,22] | 312.8 ng/mL | Standard Deviation 97.2 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Day 1 (Baseline) [n= 24,25,22,25] | 108.3 ng/mL | Standard Deviation 39.8 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 2 (Trough) [n= 22,21,20,22] | 427.2 ng/mL | Standard Deviation 178.5 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 3 (Trough)[n= 21,19,19, 20] | 404.9 ng/mL | Standard Deviation 104.4 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 4 (Trough)[n= 3,5,5,3] | 363.6 ng/mL | Standard Deviation 125.4 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 1 (Trough) [n= 24,25,22,25] | 326.9 ng/mL | Standard Deviation 108.9 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Day 1 (Baseline) [n= 24,25,22,25] | 87.1 ng/mL | Standard Deviation 31 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 2 (Trough) [n= 22,21,20,22] | 539.3 ng/mL | Standard Deviation 195.9 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Day 1 (Baseline) [n= 24,25,22,25] | 100.2 ng/mL | Standard Deviation 41.4 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 1 (Trough) [n= 24,25,22,25] | 397.8 ng/mL | Standard Deviation 185.4 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 3 (Trough)[n= 21,19,19, 20] | 462.2 ng/mL | Standard Deviation 156.4 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 4 (Trough)[n= 3,5,5,3] | 546.2 ng/mL | Standard Deviation 265.8 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 3 (Trough)[n= 21,19,19, 20] | 441.3 ng/mL | Standard Deviation 226 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 1 (Trough) [n= 24,25,22,25] | 296.0 ng/mL | Standard Deviation 126.8 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Day 1 (Baseline) [n= 24,25,22,25] | 96.7 ng/mL | Standard Deviation 38.8 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 2 (Trough) [n= 22,21,20,22] | 466.4 ng/mL | Standard Deviation 178.6 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1) | Year 4 (Trough)[n= 3,5,5,3] | 607.7 ng/mL | Standard Deviation 65 |
Secondary
Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Population: Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 3 (Trough) [n= 21,19,18,19] | 46.1 ng/mL | Standard Deviation 35.2 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 1 (Trough) [n= 24,24,21,24] | 45.7 ng/mL | Standard Deviation 38 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 4 (Trough) [n= 3,5,5,3] | 100.0 ng/mL | Standard Deviation 60.4 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 2 (Trough) [n= 22,21,19,20] | 59.4 ng/mL | Standard Deviation 45.6 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Day 1 (Baseline) [n= 24,24,21,24] | 87.8 ng/mL | Standard Deviation 54.5 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 2 (Trough) [n= 22,21,19,20] | 58.2 ng/mL | Standard Deviation 47.7 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 3 (Trough) [n= 21,19,18,19] | 60.4 ng/mL | Standard Deviation 52.5 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 4 (Trough) [n= 3,5,5,3] | 46.8 ng/mL | Standard Deviation 58 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 1 (Trough) [n= 24,24,21,24] | 63.8 ng/mL | Standard Deviation 50.1 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Day 1 (Baseline) [n= 24,24,21,24] | 102.5 ng/mL | Standard Deviation 37.2 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 2 (Trough) [n= 22,21,19,20] | 53.3 ng/mL | Standard Deviation 35.3 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Day 1 (Baseline) [n= 24,24,21,24] | 95.7 ng/mL | Standard Deviation 50 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 1 (Trough) [n= 24,24,21,24] | 68.2 ng/mL | Standard Deviation 61.6 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 3 (Trough) [n= 21,19,18,19] | 53.2 ng/mL | Standard Deviation 34.8 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 4 (Trough) [n= 3,5,5,3] | 49.2 ng/mL | Standard Deviation 20.7 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 3 (Trough) [n= 21,19,18,19] | 84.7 ng/mL | Standard Deviation 53.5 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 1 (Trough) [n= 24,24,21,24] | 88.8 ng/mL | Standard Deviation 47.4 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Day 1 (Baseline) [n= 24,24,21,24] | 122.4 ng/mL | Standard Deviation 53.7 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 2 (Trough) [n= 22,21,19,20] | 71.7 ng/mL | Standard Deviation 46.1 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) | Year 4 (Trough) [n= 3,5,5,3] | 49.0 ng/mL | Standard Deviation 26.9 |
Secondary
Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Population: Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 3 (Trough) [n= 21,19,19,20] | 3404.8 ng/mL | Standard Deviation 476.9 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 1 (Trough) [n= 24,25,22,25] | 2954.2 ng/mL | Standard Deviation 618.5 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 4 (Trough) [n= 3,5,5,3] | 3733.3 ng/mL | Standard Deviation 378.6 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 2 (Trough) [n= 22,21,20,22] | 2813.6 ng/mL | Standard Deviation 399.2 |
| rhGH Alone | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Day 1 (Baseline) [n= 24,25,22,25] | 2204.2 ng/mL | Standard Deviation 387.3 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 2 (Trough) [n= 22,21,20,22] | 2942.9 ng/mL | Standard Deviation 552.8 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 3 (Trough) [n= 21,19,19,20] | 3431.6 ng/mL | Standard Deviation 718.1 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 4 (Trough) [n= 3,5,5,3] | 3260.0 ng/mL | Standard Deviation 709.2 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 1 (Trough) [n= 24,25,22,25] | 2784.0 ng/mL | Standard Deviation 755.9 |
| 45 rhGH + 50 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Day 1 (Baseline) [n= 24,25,22,25] | 2160.0 ng/mL | Standard Deviation 421.3 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 2 (Trough) [n= 22,21,20,22] | 3060.0 ng/mL | Standard Deviation 703.7 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Day 1 (Baseline) [n= 24,25,22,25] | 2113.6 ng/mL | Standard Deviation 486.3 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 1 (Trough) [n= 24,25,22,25] | 2677.3 ng/mL | Standard Deviation 548.5 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 3 (Trough) [n= 21,19,19,20] | 3373.7 ng/mL | Standard Deviation 479.4 |
| 45 rhGH + 100 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 4 (Trough) [n= 3,5,5,3] | 3620.0 ng/mL | Standard Deviation 957.6 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 3 (Trough) [n= 21,19,19,20] | 3260.0 ng/mL | Standard Deviation 908.1 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 1 (Trough) [n= 24,25,22,25] | 2624.0 ng/mL | Standard Deviation 598.8 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Day 1 (Baseline) [n= 24,25,22,25] | 2196.0 ng/mL | Standard Deviation 612 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 2 (Trough) [n= 22,21,20,22] | 2754.5 ng/mL | Standard Deviation 600.6 |
| 45 rhGH + 150 rhIGF-1 | Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3) | Year 4 (Trough) [n= 3,5,5,3] | 3466.7 ng/mL | Standard Deviation 461.9 |
Secondary
Cumulative Change in Height Standard Deviation Score (SDS)
Height was measured standing and without shoes, and recorded as the mean of three measurements (the subject being repositioned each time) by the same observer using a Harpenden or other wall-mounted stadiometer which was to be calibrated prior to measurement of each subject and a calibration log kept. The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)
Time frame: First, second, third and fourth year
Population: Modified Intent-To-Treat (MITT): MITT population comprised all subjects who were randomized and had at least one post-baseline height measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Cumulative Change in Height Standard Deviation Score (SDS) | First year [n= 25,27,27,26] | 0.7 SDS | Standard Deviation 0.3 |
| rhGH Alone | Cumulative Change in Height Standard Deviation Score (SDS) | Second year [n= 24,25,22,24] | 1.0 SDS | Standard Deviation 0.4 |
| rhGH Alone | Cumulative Change in Height Standard Deviation Score (SDS) | Third year [n=22,22,20,22] | 1.3 SDS | Standard Deviation 0.5 |
| rhGH Alone | Cumulative Change in Height Standard Deviation Score (SDS) | Fourth year [n=17,16,15,16] | 1.5 SDS | Standard Deviation 0.5 |
| 45 rhGH + 50 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | Second year [n= 24,25,22,24] | 1.4 SDS | Standard Deviation 0.4 |
| 45 rhGH + 50 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | Third year [n=22,22,20,22] | 1.6 SDS | Standard Deviation 0.4 |
| 45 rhGH + 50 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | Fourth year [n=17,16,15,16] | 1.8 SDS | Standard Deviation 0.5 |
| 45 rhGH + 50 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | First year [n= 25,27,27,26] | 0.9 SDS | Standard Deviation 0.2 |
| 45 rhGH + 100 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | Third year [n=22,22,20,22] | 1.8 SDS | Standard Deviation 0.7 |
| 45 rhGH + 100 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | Second year [n= 24,25,22,24] | 1.4 SDS | Standard Deviation 0.5 |
| 45 rhGH + 100 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | Fourth year [n=17,16,15,16] | 2.1 SDS | Standard Deviation 0.8 |
| 45 rhGH + 100 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | First year [n= 25,27,27,26] | 0.8 SDS | Standard Deviation 0.4 |
| 45 rhGH + 150 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | Fourth year [n=17,16,15,16] | 2.0 SDS | Standard Deviation 0.7 |
| 45 rhGH + 150 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | Second year [n= 24,25,22,24] | 1.6 SDS | Standard Deviation 0.6 |
| 45 rhGH + 150 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | First year [n= 25,27,27,26] | 1.0 SDS | Standard Deviation 0.4 |
| 45 rhGH + 150 rhIGF-1 | Cumulative Change in Height Standard Deviation Score (SDS) | Third year [n=22,22,20,22] | 1.9 SDS | Standard Deviation 0.6 |
Secondary
Height Velocity
Time frame: Second, third and fourth year
Population: Modified Intent-To-Treat (MITT): MITT population comprised all subjects who were randomized and had at least one post-baseline height measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Height Velocity | Year 2 height velocity [n= 24,25,22,24] | 8.4 cm/y | Standard Deviation 1.3 |
| rhGH Alone | Height Velocity | Year 4 height velocity [n= 17,16,15,16] | 7.7 cm/y | Standard Deviation 0.9 |
| rhGH Alone | Height Velocity | Year 3 height velocity [n= 22,22,20,22] | 8.0 cm/y | Standard Deviation 1.1 |
| 45 rhGH + 50 rhIGF-1 | Height Velocity | Year 2 height velocity [n= 24,25,22,24] | 9.1 cm/y | Standard Deviation 1.2 |
| 45 rhGH + 50 rhIGF-1 | Height Velocity | Year 4 height velocity [n= 17,16,15,16] | 8.1 cm/y | Standard Deviation 0.8 |
| 45 rhGH + 50 rhIGF-1 | Height Velocity | Year 3 height velocity [n= 22,22,20,22] | 8.4 cm/y | Standard Deviation 1 |
| 45 rhGH + 100 rhIGF-1 | Height Velocity | Year 3 height velocity [n= 22,22,20,22] | 8.9 cm/y | Standard Deviation 1.3 |
| 45 rhGH + 100 rhIGF-1 | Height Velocity | Year 2 height velocity [n= 24,25,22,24] | 9.4 cm/y | Standard Deviation 1.6 |
| 45 rhGH + 100 rhIGF-1 | Height Velocity | Year 4 height velocity [n= 17,16,15,16] | 8.4 cm/y | Standard Deviation 1.2 |
| 45 rhGH + 150 rhIGF-1 | Height Velocity | Year 2 height velocity [n= 24,25,22,24] | 10.1 cm/y | Standard Deviation 1.8 |
| 45 rhGH + 150 rhIGF-1 | Height Velocity | Year 4 height velocity [n= 17,16,15,16] | 8.3 cm/y | Standard Deviation 1.3 |
| 45 rhGH + 150 rhIGF-1 | Height Velocity | Year 3 height velocity [n= 22,22,20,22] | 9.2 cm/y | Standard Deviation 1.5 |
Secondary
Predicted Adult Height (PAH)
Predicted Adult Height calculated by method, Roche-Wainer-Thissen (RWT) and mid-parental target height SDS. The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)
Time frame: At baseline (Day 1), year 1,2,3 and 4
Population: Completers, the completer population consists of all subjects that remained in the study until a specific time point (ie; Year 1, Year 2, Year 3 and Year 4).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Predicted Adult Height (PAH) | Baseline (day 1) [n=25,27,27,26] | -1.67 SDS | Standard Deviation 0.51 |
| rhGH Alone | Predicted Adult Height (PAH) | Year 1 [n= 24,25,22,25] | -1.12 SDS | Standard Deviation 0.57 |
| rhGH Alone | Predicted Adult Height (PAH) | Year 2 [n= 22,21,20,22] | -0.96 SDS | Standard Deviation 0.56 |
| rhGH Alone | Predicted Adult Height (PAH) | Year 3 [n=21,19,19,20] | -0.78 SDS | Standard Deviation 0.63 |
| rhGH Alone | Predicted Adult Height (PAH) | Year 4 [n=3,4,4,3] | -1.22 SDS | Standard Deviation 0.59 |
| rhGH Alone | Predicted Adult Height (PAH) | Mid-parental target height [n=25,27,27,26] | -0.51 SDS | Standard Deviation 0.38 |
| 45 rhGH + 50 rhIGF-1 | Predicted Adult Height (PAH) | Mid-parental target height [n=25,27,27,26] | -0.64 SDS | Standard Deviation 0.52 |
| 45 rhGH + 50 rhIGF-1 | Predicted Adult Height (PAH) | Year 3 [n=21,19,19,20] | -0.65 SDS | Standard Deviation 0.6 |
| 45 rhGH + 50 rhIGF-1 | Predicted Adult Height (PAH) | Baseline (day 1) [n=25,27,27,26] | -1.83 SDS | Standard Deviation 0.58 |
| 45 rhGH + 50 rhIGF-1 | Predicted Adult Height (PAH) | Year 2 [n= 22,21,20,22] | -0.81 SDS | Standard Deviation 0.55 |
| 45 rhGH + 50 rhIGF-1 | Predicted Adult Height (PAH) | Year 1 [n= 24,25,22,25] | -1.22 SDS | Standard Deviation 0.58 |
| 45 rhGH + 50 rhIGF-1 | Predicted Adult Height (PAH) | Year 4 [n=3,4,4,3] | -0.44 SDS | Standard Deviation 0.81 |
| 45 rhGH + 100 rhIGF-1 | Predicted Adult Height (PAH) | Year 1 [n= 24,25,22,25] | -0.99 SDS | Standard Deviation 0.55 |
| 45 rhGH + 100 rhIGF-1 | Predicted Adult Height (PAH) | Year 2 [n= 22,21,20,22] | -0.66 SDS | Standard Deviation 0.56 |
| 45 rhGH + 100 rhIGF-1 | Predicted Adult Height (PAH) | Year 3 [n=21,19,19,20] | -0.42 SDS | Standard Deviation 0.62 |
| 45 rhGH + 100 rhIGF-1 | Predicted Adult Height (PAH) | Mid-parental target height [n=25,27,27,26] | -0.53 SDS | Standard Deviation 0.5 |
| 45 rhGH + 100 rhIGF-1 | Predicted Adult Height (PAH) | Year 4 [n=3,4,4,3] | 0.49 SDS | Standard Deviation 0.6 |
| 45 rhGH + 100 rhIGF-1 | Predicted Adult Height (PAH) | Baseline (day 1) [n=25,27,27,26] | -1.69 SDS | Standard Deviation 0.59 |
| 45 rhGH + 150 rhIGF-1 | Predicted Adult Height (PAH) | Year 4 [n=3,4,4,3] | -0.07 SDS | Standard Deviation 0.89 |
| 45 rhGH + 150 rhIGF-1 | Predicted Adult Height (PAH) | Mid-parental target height [n=25,27,27,26] | -0.47 SDS | Standard Deviation 0.51 |
| 45 rhGH + 150 rhIGF-1 | Predicted Adult Height (PAH) | Year 1 [n= 24,25,22,25] | -1.01 SDS | Standard Deviation 0.8 |
| 45 rhGH + 150 rhIGF-1 | Predicted Adult Height (PAH) | Year 3 [n=21,19,19,20] | -0.64 SDS | Standard Deviation 0.98 |
| 45 rhGH + 150 rhIGF-1 | Predicted Adult Height (PAH) | Baseline (day 1) [n=25,27,27,26] | -1.76 SDS | Standard Deviation 0.73 |
| 45 rhGH + 150 rhIGF-1 | Predicted Adult Height (PAH) | Year 2 [n= 22,21,20,22] | -0.69 SDS | Standard Deviation 0.91 |
Secondary
Skeletal Maturation
Assessed by bone age. Bone age was determined by the radiograph. The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)
Time frame: At baseline(day 1), year 1,2,3 and 4
Population: Completers, the completer population consists of all subjects that remained in the study until a specific time point (ie; Year 1, Year 2, Year 3 and Year 4).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Skeletal Maturation | Year 3 [n=21,19,19,20] | 11.4 SDS | Standard Deviation 2 |
| rhGH Alone | Skeletal Maturation | Year 1 [n= 24,25,22,25] | 9.0 SDS | Standard Deviation 1.9 |
| rhGH Alone | Skeletal Maturation | Year 4 [n=3,4,5,3] | 12.4 SDS | Standard Deviation 1 |
| rhGH Alone | Skeletal Maturation | Year 2 [n= 22,21,20,22] | 10.3 SDS | Standard Deviation 2 |
| rhGH Alone | Skeletal Maturation | Baseline [n=25,27,27,26] | 7.6 SDS | Standard Deviation 1.8 |
| 45 rhGH + 50 rhIGF-1 | Skeletal Maturation | Year 2 [n= 22,21,20,22] | 9.6 SDS | Standard Deviation 2.1 |
| 45 rhGH + 50 rhIGF-1 | Skeletal Maturation | Year 3 [n=21,19,19,20] | 10.9 SDS | Standard Deviation 2.2 |
| 45 rhGH + 50 rhIGF-1 | Skeletal Maturation | Year 4 [n=3,4,5,3] | 10.9 SDS | Standard Deviation 1.8 |
| 45 rhGH + 50 rhIGF-1 | Skeletal Maturation | Year 1 [n= 24,25,22,25] | 8.5 SDS | Standard Deviation 1.9 |
| 45 rhGH + 50 rhIGF-1 | Skeletal Maturation | Baseline [n=25,27,27,26] | 7.3 SDS | Standard Deviation 1.9 |
| 45 rhGH + 100 rhIGF-1 | Skeletal Maturation | Year 2 [n= 22,21,20,22] | 9.8 SDS | Standard Deviation 2.4 |
| 45 rhGH + 100 rhIGF-1 | Skeletal Maturation | Baseline [n=25,27,27,26] | 7.2 SDS | Standard Deviation 2 |
| 45 rhGH + 100 rhIGF-1 | Skeletal Maturation | Year 1 [n= 24,25,22,25] | 8.4 SDS | Standard Deviation 2.2 |
| 45 rhGH + 100 rhIGF-1 | Skeletal Maturation | Year 3 [n=21,19,19,20] | 11.4 SDS | Standard Deviation 2.4 |
| 45 rhGH + 100 rhIGF-1 | Skeletal Maturation | Year 4 [n=3,4,5,3] | 12.2 SDS | Standard Deviation 3 |
| 45 rhGH + 150 rhIGF-1 | Skeletal Maturation | Year 3 [n=21,19,19,20] | 10.9 SDS | Standard Deviation 2.2 |
| 45 rhGH + 150 rhIGF-1 | Skeletal Maturation | Year 1 [n= 24,25,22,25] | 8.5 SDS | Standard Deviation 2.1 |
| 45 rhGH + 150 rhIGF-1 | Skeletal Maturation | Baseline [n=25,27,27,26] | 7.4 SDS | Standard Deviation 2 |
| 45 rhGH + 150 rhIGF-1 | Skeletal Maturation | Year 2 [n= 22,21,20,22] | 9.9 SDS | Standard Deviation 2.2 |
| 45 rhGH + 150 rhIGF-1 | Skeletal Maturation | Year 4 [n=3,4,5,3] | 12.5 SDS | Standard Deviation 2.1 |
Secondary
Summary of Adverse Events With Number of Occurrences
A Data Monitoring Committee (DMC) was established to monitor subject safety
Time frame: Approximately up to 4 years.
Population: Safety population: Safety population consisted of all subjects who were randomized. Note that post baseline follow-up data were received for all subjects who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Related and Severe | 1 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Moderate TEAE | 60 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Related and Mild | 21 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Deaths | 0 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | SAEs | 1 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Mild TEAE | 309 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Severe TEAEs | 5 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Any TEAE | 374 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Related and Moderate | 5 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Related TEAEs | 27 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | Any Adverse Event | 381 Number of events |
| rhGH Alone | Summary of Adverse Events With Number of Occurrences | TEAEs Leading to Study Withdrawal | 18 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Any TEAE | 406 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related and Severe | 1 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Any Adverse Event | 416 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related and Mild | 48 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related and Moderate | 4 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Severe TEAEs | 5 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | SAEs | 6 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Moderate TEAE | 55 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Deaths | 0 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Mild TEAE | 346 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | TEAEs Leading to Study Withdrawal | 17 Number of events |
| 45 rhGH + 50 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related TEAEs | 53 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related and Moderate | 18 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Any Adverse Event | 401 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Any TEAE | 392 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Severe TEAEs | 3 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Moderate TEAE | 57 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Mild TEAE | 332 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related TEAEs | 74 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related and Severe | 1 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related and Mild | 55 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | TEAEs Leading to Study Withdrawal | 36 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | SAEs | 2 Number of events |
| 45 rhGH + 100 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Deaths | 0 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related TEAEs | 119 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Mild TEAE | 424 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Any Adverse Event | 518 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | TEAEs Leading to Study Withdrawal | 6 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Moderate TEAE | 86 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Severe TEAEs | 3 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Deaths | 0 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | SAEs | 1 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related and Moderate | 13 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related and Severe | 0 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Any TEAE | 513 Number of events |
| 45 rhGH + 150 rhIGF-1 | Summary of Adverse Events With Number of Occurrences | Related and Mild | 106 Number of events |
Secondary
Total Change From Baseline (Day 1) in BMI SDS
BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). The SDS was calculated as: SDS=\[(value /M)\^L - 1\] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)
Time frame: At year 1,2,3,4 and end of study (visit 23) versus baseline (day 1)
Population: Completers, the completer population consists of all subjects that remained in the study until a specific time point (ie; Year 1, Year 2, Year 3 and Year 4).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhGH Alone | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 4 [n=3,5,5,4] | 0.27 SDS | Standard Deviation 0.52 |
| rhGH Alone | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 2 [n= 22,21,20,22] | 0.31 SDS | Standard Deviation 0.49 |
| rhGH Alone | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to visit 23 [n=25,27,27,26] | 0.34 SDS | Standard Deviation 0.54 |
| rhGH Alone | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 3 [n=21,19,19,20] | 0.35 SDS | Standard Deviation 0.58 |
| rhGH Alone | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 1 [n= 24,25,22,25] | 0.24 SDS | Standard Deviation 0.43 |
| 45 rhGH + 50 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 3 [n=21,19,19,20] | 0.62 SDS | Standard Deviation 0.43 |
| 45 rhGH + 50 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 4 [n=3,5,5,4] | 0.64 SDS | Standard Deviation 0.58 |
| 45 rhGH + 50 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to visit 23 [n=25,27,27,26] | 0.45 SDS | Standard Deviation 0.45 |
| 45 rhGH + 50 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 2 [n= 22,21,20,22] | 0.57 SDS | Standard Deviation 0.41 |
| 45 rhGH + 50 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 1 [n= 24,25,22,25] | 0.31 SDS | Standard Deviation 0.39 |
| 45 rhGH + 100 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 3 [n=21,19,19,20] | 0.49 SDS | Standard Deviation 0.59 |
| 45 rhGH + 100 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 1 [n= 24,25,22,25] | 0.36 SDS | Standard Deviation 0.41 |
| 45 rhGH + 100 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 2 [n= 22,21,20,22] | 0.49 SDS | Standard Deviation 0.44 |
| 45 rhGH + 100 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 4 [n=3,5,5,4] | 0.65 SDS | Standard Deviation 0.9 |
| 45 rhGH + 100 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to visit 23 [n=25,27,27,26] | 0.42 SDS | Standard Deviation 0.53 |
| 45 rhGH + 150 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 4 [n=3,5,5,4] | 1.20 SDS | Standard Deviation 0.91 |
| 45 rhGH + 150 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 2 [n= 22,21,20,22] | 0.59 SDS | Standard Deviation 0.46 |
| 45 rhGH + 150 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 1 [n= 24,25,22,25] | 0.54 SDS | Standard Deviation 0.4 |
| 45 rhGH + 150 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to year 3 [n=21,19,19,20] | 0.71 SDS | Standard Deviation 0.54 |
| 45 rhGH + 150 rhIGF-1 | Total Change From Baseline (Day 1) in BMI SDS | Change from day 1 to visit 23 [n=25,27,27,26] | 0.64 SDS | Standard Deviation 0.6 |