Infant, Small for Gestational Age
Conditions
Brief summary
To demonstrate the effect on height and psychomotor development of Growth Hormone treatment in very young children starting at an age of 2 years.
Interventions
Injectable Genotropin
Control-no treatment
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Months to 29 Months
Healthy volunteers
No
Inclusion criteria
Caucasian male or female subjects aged between 19-29 months at Screening Visit 1. Born SGA (birth length and/or weight \<-2 SD for gestational age, using country-specific standards). Height below -2.5 SD at screening (19-29 months of age). At least one measurement of length between 12 and 18 months of age. Normal karyotype in girls to exclude Turners syndrome.
Exclusion criteria
Severe Intra-Uterine Growth Retardation (IUGR) (birth length below - 4 SD for gestational age), if associated with dysmorphic features. Severe prematurity (Gestational Age (GA) \<32 weeks of gestation). Ongoing catch-up growth (defined as growth velocity SDS at inclusion \>0) based on at least 4 months measurement interval). Severe familial short stature defined as: Father's height below 155 cm or mother's height below 145 cm. Defined neurological defects and/or severe neurodevelopmental delay.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Height Standard Deviation Score (SDS) at Month 24. | Baseline and Month 24 | Height SDS was calculated at the relevant visit by means of the following formula: Height SDS = (participant height) - (normal height)/normal height standard deviation. Where participant height refers to the participant's height at the relevant visit, and normal height and the normal height standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for height SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. The scores were centred around zero. Negative score indicated a participant was smaller for their age/gender. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Height SDS at Month 12. | Baseline and Month 12 | Height SDS was calculated at the relevant visit by means of the following formula: Height SDS = (participant height) - (normal height)/normal height standard deviation. Where participant height refers to the participant's height at the relevant visit, and normal height and the normal height standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for height SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. The scores were centred around zero. Negative score indicated a participant was smaller for their age/gender. |
| Change From Baseline in Growth Velocity SDS at Month 12. | Baseline and Month 12 | The growth velocity SDS was calculated at the relevant visit by means of the following formula: Growth velocity SDS = (participant growth velocity) - (normal growth velocity)/normal growth velocity standard deviation. Where, participant growth velocity refers to the participant's growth velocity at the relevant visit, and normal growth velocity and the normal growth velocity standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for growth velocity SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. A negative score indicated that a participant had slower growth for their age/gender. |
| Change From Baseline in Mental Development Using the Mental Development Index (MDI) of Bayley Scale at Month 12. | Baseline and Month 12 | The Bayley Scale of Infant Development (BSID-II) measured the mental and psychomotor development and test behavior of participants from 1 to 42 months of age. The scale was used to describe the current developmental functioning of infants and to assist in diagnosis and treatment planning for infants with developmental delays or disabilities. The BSID-II provided the mental raw score which was used to calculate the MDI score. Possible MDI scores ranged from 50-150. A score of 69 and below indicates significantly delayed performance, 70 to 84 indicates mildly delayed performance, 85 to 114 indicates normal limits and 115 and above indicates accelerated performance. |
| Change From Baseline in Psychomotor Development Using the Psychomotor Development Index (PDI) of Bayley Scale at Month 12. | Baseline and Month 12 | BSID-II measured the mental and psychomotor development and test behavior of participants from 1 to 42 months of age. The scale was used to describe the current developmental functioning of infants and to assist in diagnosis and treatment planning for infants with developmental delays or disabilities. The BSID-II provided the psychomotor raw score which was used to calculate the PDI score. Possible PDI scores ranged from 50-150. A score of 69 and below indicates significantly delayed performance, 70 to 84 indicates mildly delayed performance, 85 to 114 indicates normal limits and 115 and above indicates accelerated performance. |
| Change From Baseline in Growth Velocity SDS at Month 24. | Baseline and Month 24 | The growth velocity SDS was calculated at the relevant visit by means of the following formula: Growth velocity SDS = (participant growth velocity) - (normal growth velocity)/normal growth velocity standard deviation. Where, participant growth velocity refers to the participant's growth velocity at the relevant visit, and normal growth velocity and the normal growth velocity standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for growth velocity SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. A negative score indicated that a participant had slower growth for their age/gender. |
| Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Baseline, Months 3, 6, 12, 18 and 24. | Head circumference SDS was calculated by means of the following formula = (Participant head circumference)-(Normal head circumference)/Normal head circumference standard deviation. Where participant head circumference refers to the participant's head circumference at the relevant visit, and normal head circumference and the normal head circumference standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. A negative score indicated a participant had a smaller head circumference for their age/gender. |
| Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Baseline, Months 3, 6, 12, 18, and 24 | Body weight was measured at all the relevant visits. The change from Baseline in body weight was calculated as the difference between the parameter values at each visit, and the Baseline parameter values. |
| Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Baseline, Months 3, 6, 12, 18, and 24 | Body mass index was calculated for all visits by means of the following formula: BMI (kg/m2) = Weight (kg)/(Height\[m\])2. The change from Baseline BMI was calculated as the difference between the parameter values at each visit, and the Baseline parameter values. |
| Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Months 3, 6, 12, 18 and 24 | Head circumference SDS was calculated by means of the following formula = (Participant head circumference)-(Normal head circumference)/ Normal head circumference standard deviation. Where participant head circumference refers to the participant's head circumference at the relevant visit, and normal head circumference and the normal head circumference standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. A negative score indicated a participant had a smaller head circumference for their age/gender. |
Countries
Belgium, Czechia, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland
Participant flow
Recruitment details
This randomized controlled trial enrolled small for gestational age (SGA) children at 16 centers in 8 countries. In total, 52 participants were screened for the study, of these, 9 participants were considered screen failures. The remaining 43 participants were randomized to receive either study drug (Genotropin®) or were not treated (Control).
Pre-assignment details
Participants aged between 19 to 29 months at Screening visit, born SGA (birth length and/or weight \<-2 standard deviations (SD) for gestational age, using country-specific standards), height below -2.5 SD at Screening (19-29 months of age), and had at least one measurement of length between 12 and 18 months of age were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Genotropin® Participants received Genotropin® at a dose of 0.035 mg/kg/d for 24 months. The dose was calculated based on the actual body weight, and the closest dosing step of the 5 mg pen used. The starting dose for the first 2 weeks was 1/3 of the calculated dose. After 2 weeks the dose was increased to 2/3 of the calculated dose. After 4 weeks the daily dose was the dose calculated on body weight at randomization. | 21 |
| Control This group was the untreated control group and was not administered placebo. | 22 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Genotropin® | Control | Total |
|---|---|---|---|
| Age, Continuous | 24.91 Months STANDARD_DEVIATION 3.262 | 24.44 Months STANDARD_DEVIATION 3.324 | 24.67 Months STANDARD_DEVIATION 3.263 |
| Sex: Female, Male Female | 13 Participants | 11 Participants | 24 Participants |
| Sex: Female, Male Male | 8 Participants | 11 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 21 | 18 / 22 |
| serious Total, serious adverse events | 6 / 21 | 2 / 22 |
Outcome results
Primary
Change From Baseline in Height Standard Deviation Score (SDS) at Month 24.
Height SDS was calculated at the relevant visit by means of the following formula: Height SDS = (participant height) - (normal height)/normal height standard deviation. Where participant height refers to the participant's height at the relevant visit, and normal height and the normal height standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for height SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. The scores were centred around zero. Negative score indicated a participant was smaller for their age/gender.
Time frame: Baseline and Month 24
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. Missing values were imputed using LOCF method. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control for safety analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Genotropin® | Change From Baseline in Height Standard Deviation Score (SDS) at Month 24. | 1.63 SDS | Standard Error 0.13 |
| Control | Change From Baseline in Height Standard Deviation Score (SDS) at Month 24. | 0.43 SDS | Standard Error 0.13 |
Comparison: The null hypothesis was that there was no difference in the mean change from Baseline after 24 months in height SDS between the Genotropin® and the untreated control groups. The alternative hypothesis was that there was a difference between the treatment groups.p-value: <0.00195% CI: [0.82, 1.59]ANCOVA
Secondary
Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24.
Body mass index was calculated for all visits by means of the following formula: BMI (kg/m2) = Weight (kg)/(Height\[m\])2. The change from Baseline BMI was calculated as the difference between the parameter values at each visit, and the Baseline parameter values.
Time frame: Baseline, Months 3, 6, 12, 18, and 24
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control group for safety analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotropin® | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 6 (n = 21, 20) | -0.57 Kg/m2 | Standard Deviation 0.537 |
| Genotropin® | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 18 (n = 20, 19) | -0.78 Kg/m2 | Standard Deviation 0.93 |
| Genotropin® | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 12 (n = 20, 19) | -0.62 Kg/m2 | Standard Deviation 0.65 |
| Genotropin® | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 24 (n = 20, 20) | -0.58 Kg/m2 | Standard Deviation 0.823 |
| Genotropin® | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 3 (n = 21, 19) | -0.28 Kg/m2 | Standard Deviation 0.419 |
| Control | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 24 (n = 20, 20) | -0.55 Kg/m2 | Standard Deviation 0.776 |
| Control | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 3 (n = 21, 19) | -0.05 Kg/m2 | Standard Deviation 0.811 |
| Control | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 6 (n = 21, 20) | 0.08 Kg/m2 | Standard Deviation 1.013 |
| Control | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 12 (n = 20, 19) | -0.29 Kg/m2 | Standard Deviation 0.683 |
| Control | Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Month 18 (n = 20, 19) | -0.25 Kg/m2 | Standard Deviation 0.806 |
Secondary
Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24.
Body weight was measured at all the relevant visits. The change from Baseline in body weight was calculated as the difference between the parameter values at each visit, and the Baseline parameter values.
Time frame: Baseline, Months 3, 6, 12, 18, and 24
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control group for safety analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotropin® | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 6 (n = 21, 20) | 1.08 Kg | Standard Deviation 0.269 |
| Genotropin® | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 18 (n = 20, 19) | 3.48 Kg | Standard Deviation 0.669 |
| Genotropin® | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 12 (n = 20, 19) | 2.34 Kg | Standard Deviation 0.389 |
| Genotropin® | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 24 (n = 20, 20) | 4.79 Kg | Standard Deviation 0.814 |
| Genotropin® | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 3 (n = 21, 19) | 0.57 Kg | Standard Deviation 0.154 |
| Control | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 24 (n = 20, 20) | 3.19 Kg | Standard Deviation 0.601 |
| Control | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 3 (n = 21, 19) | 0.53 Kg | Standard Deviation 0.406 |
| Control | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 6 (n = 21, 20) | 1.01 Kg | Standard Deviation 0.659 |
| Control | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 12 (n = 20, 19) | 1.66 Kg | Standard Deviation 0.397 |
| Control | Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Month 18 (n = 20, 19) | 2.41 Kg | Standard Deviation 0.709 |
Secondary
Change From Baseline in Growth Velocity SDS at Month 12.
The growth velocity SDS was calculated at the relevant visit by means of the following formula: Growth velocity SDS = (participant growth velocity) - (normal growth velocity)/normal growth velocity standard deviation. Where, participant growth velocity refers to the participant's growth velocity at the relevant visit, and normal growth velocity and the normal growth velocity standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for growth velocity SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. A negative score indicated that a participant had slower growth for their age/gender.
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. Missing values were imputed using LOCF method. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control for safety analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Genotropin® | Change From Baseline in Growth Velocity SDS at Month 12. | 1.65 SDS | Standard Error 0.56 |
| Control | Change From Baseline in Growth Velocity SDS at Month 12. | -1.59 SDS | Standard Error 0.56 |
Comparison: The null hypothesis was that there was no difference between the Genotropin® and the untreated control group in terms of the relevant secondary endpoints. The alternative hypothesis was that a difference existed.p-value: <0.00195% CI: [1.63, 4.85]ANCOVA
Secondary
Change From Baseline in Growth Velocity SDS at Month 24.
The growth velocity SDS was calculated at the relevant visit by means of the following formula: Growth velocity SDS = (participant growth velocity) - (normal growth velocity)/normal growth velocity standard deviation. Where, participant growth velocity refers to the participant's growth velocity at the relevant visit, and normal growth velocity and the normal growth velocity standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for growth velocity SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. A negative score indicated that a participant had slower growth for their age/gender.
Time frame: Baseline and Month 24
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. Missing values were imputed using LOCF method. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control for safety analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Genotropin® | Change From Baseline in Growth Velocity SDS at Month 24. | 0.74 SDS | Standard Error 0.57 |
| Control | Change From Baseline in Growth Velocity SDS at Month 24. | -0.03 SDS | Standard Error 0.57 |
Comparison: The null hypothesis was that there was no difference between the Genotropin® and the untreated control group in terms of the relevant secondary endpoints. The alternative hypothesis was that a difference existed.p-value: 0.34895% CI: [-0.87, 2.42]ANCOVA
Secondary
Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24.
Head circumference SDS was calculated by means of the following formula = (Participant head circumference)-(Normal head circumference)/Normal head circumference standard deviation. Where participant head circumference refers to the participant's head circumference at the relevant visit, and normal head circumference and the normal head circumference standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. A negative score indicated a participant had a smaller head circumference for their age/gender.
Time frame: Baseline, Months 3, 6, 12, 18 and 24.
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control group for safety analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotropin® | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 6 (n = 21, 19) | -0.00 SDS | Standard Deviation 0.423 |
| Genotropin® | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 18 (n = 20, 19) | 0.57 SDS | Standard Deviation 1.094 |
| Genotropin® | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 12 (n = 20, 18) | 0.26 SDS | Standard Deviation 0.516 |
| Genotropin® | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 24 (n = 20, 20) | 0.39 SDS | Standard Deviation 0.638 |
| Genotropin® | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 3 (n = 21, 19) | 0.27 SDS | Standard Deviation 0.977 |
| Control | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 24 (n = 20, 20) | 0.08 SDS | Standard Deviation 0.602 |
| Control | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 3 (n = 21, 19) | 0.36 SDS | Standard Deviation 0.693 |
| Control | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 6 (n = 21, 19) | 0.07 SDS | Standard Deviation 0.495 |
| Control | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 12 (n = 20, 18) | 0.02 SDS | Standard Deviation 0.587 |
| Control | Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 18 (n = 20, 19) | 0.04 SDS | Standard Deviation 0.506 |
Secondary
Change From Baseline in Height SDS at Month 12.
Height SDS was calculated at the relevant visit by means of the following formula: Height SDS = (participant height) - (normal height)/normal height standard deviation. Where participant height refers to the participant's height at the relevant visit, and normal height and the normal height standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for height SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. The scores were centred around zero. Negative score indicated a participant was smaller for their age/gender.
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. Missing values were imputed using LOCF method. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control for safety analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Genotropin® | Change From Baseline in Height SDS at Month 12. | 1.03 SDS | Standard Error 0.12 |
| Control | Change From Baseline in Height SDS at Month 12. | 0.14 SDS | Standard Error 0.12 |
Comparison: The null hypothesis was that there was no difference between the Genotropin® and the untreated control group in terms of the relevant secondary endpoints. The alternative hypothesis was that a difference existed.p-value: <0.00195% CI: [0.55, 1.23]ANCOVA
Secondary
Change From Baseline in Mental Development Using the Mental Development Index (MDI) of Bayley Scale at Month 12.
The Bayley Scale of Infant Development (BSID-II) measured the mental and psychomotor development and test behavior of participants from 1 to 42 months of age. The scale was used to describe the current developmental functioning of infants and to assist in diagnosis and treatment planning for infants with developmental delays or disabilities. The BSID-II provided the mental raw score which was used to calculate the MDI score. Possible MDI scores ranged from 50-150. A score of 69 and below indicates significantly delayed performance, 70 to 84 indicates mildly delayed performance, 85 to 114 indicates normal limits and 115 and above indicates accelerated performance.
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control group for safety analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Genotropin® | Change From Baseline in Mental Development Using the Mental Development Index (MDI) of Bayley Scale at Month 12. | 10.97 Units on a scale | Standard Error 5.34 |
| Control | Change From Baseline in Mental Development Using the Mental Development Index (MDI) of Bayley Scale at Month 12. | 8.55 Units on a scale | Standard Error 4.74 |
Comparison: The null hypothesis was that there was no difference between the Genotropin® and the untreated control group in terms of the relevant secondary endpoints. The alternative hypothesis was that a difference existed.p-value: 0.73895% CI: [-12.27, 17.12]ANCOVA
Secondary
Change From Baseline in Psychomotor Development Using the Psychomotor Development Index (PDI) of Bayley Scale at Month 12.
BSID-II measured the mental and psychomotor development and test behavior of participants from 1 to 42 months of age. The scale was used to describe the current developmental functioning of infants and to assist in diagnosis and treatment planning for infants with developmental delays or disabilities. The BSID-II provided the psychomotor raw score which was used to calculate the PDI score. Possible PDI scores ranged from 50-150. A score of 69 and below indicates significantly delayed performance, 70 to 84 indicates mildly delayed performance, 85 to 114 indicates normal limits and 115 and above indicates accelerated performance.
Time frame: Baseline and Month 12
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control group for safety analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Genotropin® | Change From Baseline in Psychomotor Development Using the Psychomotor Development Index (PDI) of Bayley Scale at Month 12. | 4.04 Units on a scale | Standard Error 3.04 |
| Control | Change From Baseline in Psychomotor Development Using the Psychomotor Development Index (PDI) of Bayley Scale at Month 12. | 8.55 Units on a scale | Standard Error 2.84 |
Comparison: The null hypothesis was that there was no difference between the Genotropin® and the untreated control group in terms of the relevant secondary endpoints. The alternative hypothesis was that a difference existed.p-value: 0.30195% CI: [-13.27, 4.26]ANCOVA
Secondary
Head Circumference SDS at Months 3, 6, 12, 18 and 24.
Head circumference SDS was calculated by means of the following formula = (Participant head circumference)-(Normal head circumference)/ Normal head circumference standard deviation. Where participant head circumference refers to the participant's head circumference at the relevant visit, and normal head circumference and the normal head circumference standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. A negative score indicated a participant had a smaller head circumference for their age/gender.
Time frame: Months 3, 6, 12, 18 and 24
Population: Full Analysis Set (FAS) included participants who were randomized to treatment and completed at least one post-baseline efficacy measure. One participant was randomized to Genotropin® but did not receive any treatment. This participant was excluded from FAS but included in Control group for safety analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotropin® | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 3 (n = 21, 19) | -0.93 SDS | Standard Deviation 1.217 |
| Genotropin® | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 12 (n = 20, 18) | -0.87 SDS | Standard Deviation 1.33 |
| Genotropin® | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 24 (n = 20, 20) | -0.75 SDS | Standard Deviation 1.384 |
| Genotropin® | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 18 (n = 20, 19) | -0.56 SDS | Standard Deviation 1.89 |
| Genotropin® | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 6 (n = 21, 19) | -1.20 SDS | Standard Deviation 1.31 |
| Control | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 24 (n = 20, 20) | -1.65 SDS | Standard Deviation 1.227 |
| Control | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 3 (n = 21, 19) | -1.37 SDS | Standard Deviation 1.122 |
| Control | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 6 (n = 21, 19) | -1.72 SDS | Standard Deviation 1.077 |
| Control | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 12 (n = 20, 18) | -1.84 SDS | Standard Deviation 1.158 |
| Control | Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Month 18 (n = 20, 19) | -1.76 SDS | Standard Deviation 1.153 |