Trial Outcomes & Findings for Somatropin Therapy In Children Born Preterm But Appropriate For Gestational Age (NCT NCT00174460)

Last Updated: 2017-04-05

Results Overview

Change in Height SDS after 1 year where SDS=height minus mean (age-and sex-matched reference) divided by SD (age and sex-matched reference).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

Baseline to 1 year (Month 12)

Results posted on

2017-04-05

Participant Flow

Participant milestones

Participant milestones
Measure	Somatropin The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Overall Study STARTED	18	15
Overall Study Received Study Treatment	18	14
Overall Study COMPLETED	18	14
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Somatropin The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Somatropin Therapy In Children Born Preterm But Appropriate For Gestational Age

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.	Total n=33 Participants Total of all reporting groups
Age, Continuous	5.4 years STANDARD_DEVIATION 1.6 • n=5 Participants	5.7 years STANDARD_DEVIATION 1.9 • n=7 Participants	5.5 years STANDARD_DEVIATION 1.7 • n=5 Participants
Age, Customized <4 years	1 Participants 1.5 • n=5 Participants	1 Participants 1.9 • n=7 Participants	2 Participants 1.7 • n=5 Participants
Age, Customized ≥4 years and <8 years	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Age, Customized ≥8 years and <12 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 1 year (Month 12)

Population: Full Analysis Set (FAS; all randomized subjects who had at least 1 post-baseline efficacy measurement); Control group received Somatropin from Month 12 onwards.

Change in Height SDS after 1 year where SDS=height minus mean (age-and sex-matched reference) divided by SD (age and sex-matched reference).

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change in Height Standard Deviation Score (SDS) After 1 Year	1.099 centimeters Standard Error 0.0714	0.108 centimeters Standard Error 0.0783

PRIMARY outcome

Timeframe: Baseline to 1 year (Month 12)

Population: FAS; Control group received Somatropin from Month 12 onwards.

Change in Growth Velocity (GV) SDS after 1 year where SDS=GV minus mean (age-and sex-matched reference) divided by SD (age and sex-matched reference).

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change in Growth Velocity Standard Deviation Score (SDS) After 1 Year	7.117 centimeters per year Standard Error 0.4384	1.502 centimeters per year Standard Error 0.4814

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards.

Growth velocity measured as centimeters per year.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Growth Velocity After 1 Year and After 2 Years Month 12	5.110 centimeters per year Standard Error 0.2623	0.695 centimeters per year Standard Error 0.2881
Change From Baseline in Growth Velocity After 1 Year and After 2 Years Month 24	3.049 centimeters per year Standard Error 0.3546	3.934 centimeters per year Standard Error 0.3893

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards.

Change in Growth Velocity SDS after 2 years (24 months) where SDS = growth velocity minus mean (age-and sex-matched reference) divided by SD (age and sex-matched reference).

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Growth Velocity SDS After 2 Years	4.751 centimeters per year Standard Error 0.4716	5.825 centimeters per year Standard Error 0.5177

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Height After 1 Year and After 2 Years Month 12	10.467 centimeters Standard Error 0.2439	5.927 centimeters Standard Error 0.2677
Change From Baseline in Height After 1 Year and After 2 Years Month 24	18.908 centimeters Standard Error 0.6507	14.844 centimeters Standard Error 0.7149

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards.

Change in Height SDS after 2 years (24 months) where SDS = height minus mean (age-and sex-matched reference) divided by SD (age and sex-matched reference).

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Height SDS After 2 Years	1.710 centimeters Standard Error 0.1075	0.991 centimeters Standard Error 0.1179

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards. N=number of participants with evaluable data at observation.

Body composition measured as skinfold thickness at tricep in millimeters (mm); measured halfway down the left upper arm with arm hanging in relaxed position at participant's side.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Body Composition (Skinfold Thickness) After 1 Year and After 2 Years: Triceps Month 12	-2.20 millimeters Standard Error 0.341	0.50 millimeters Standard Error 0.353
Change From Baseline in Body Composition (Skinfold Thickness) After 1 Year and After 2 Years: Triceps Month 24	-1.30 millimeters Standard Error 0.511	-0.83 millimeters Standard Error 0.548

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards. N=number of participants with evaluable data at observation.

Body composition measured as subscapular skinfold thickness in millimeters (mm); measured laterally just below the angle of the left scapula.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Body Composition (Skinfold Thickness) After 1 Year and After 2 Years: Subscapular Month 12	0.08 millimeters Standard Error 0.276	0.46 millimeters Standard Error 0.286
Change From Baseline in Body Composition (Skinfold Thickness) After 1 Year and After 2 Years: Subscapular Month 24	0.27 millimeters Standard Error 0.231	0.50 millimeters Standard Error 0.247

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards. N=number of participants with evaluable data at observation.

Body composition measured as suprailiac skinfold thickness in millimeters (mm); measured just above the iliac crest in the middle-axillary line.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Body Composition (Skinfold Thickness) After 1 Year and After 2 Years: Suprailiac Month 12	0.51 millimeters Standard Error 0.783	0.45 millimeters Standard Error 0.849
Change From Baseline in Body Composition (Skinfold Thickness) After 1 Year and After 2 Years: Suprailiac Month 24	0.90 millimeters Standard Error 0.688	0.79 millimeters Standard Error 0.774

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards; (n)=number of participants from FAS with evaluable pQCT data for somatropin and control arm groups, respectively.

Volumetric Cortical BMD measured as milligrams per cubic millimeter (mg/mm3). BMD (proximal radius) SDS (number of standard deviations a participant's BMD differs from the average BMD of their age and sex). Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)\]/S); Ln=natural logarithm; M=age- or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Volumetric Cortical Bone Mineral Density (BMD) Using Peripheral Quantitative Computed Tomography (pQCT) After 1 Year and After 2 Years Month 12 (n=2, 6)	-1.055 z-score Standard Error 0.6802	-0.162 z-score Standard Error 0.3600
Change From Baseline in Volumetric Cortical Bone Mineral Density (BMD) Using Peripheral Quantitative Computed Tomography (pQCT) After 1 Year and After 2 Years Month 24 (n=2, 6)	0.284 z-score Standard Error 0.5023	-0.433 z-score Standard Error 0.2658

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards; (n)=number of participants from FAS with evaluable pQCT data for somatropin and control arm groups, respectively.

Bone structure Cortical CSA measured as millimeters squared (mm2). CSA (proximal radius) SDS (number of standard deviations a participant's CSA differs from the average CSA of their age and sex). Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)\]/S); Ln=natural logarithm; M=age- or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Bone Structure Using pQCT After 1 Year and 2 Years: Cortical Cross-sectional Area (CSA) Month 12 (n=2, 5)	-0.465 z-score Standard Error 0.7799	0.017 z-score Standard Error 0.4559
Change From Baseline in Bone Structure Using pQCT After 1 Year and 2 Years: Cortical Cross-sectional Area (CSA) Month 24 (n=2, 6)	-0.595 z-score Standard Error 0.7462	0.609 z-score Standard Error 0.3907

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards; (n)=number of participants from FAS with evaluable pQCT data for somatropin and control arm groups, respectively.

Bone structure Total CSA measured as millimeters squared (mm2). Total CSA (proximal radius) SDS (number of standard deviations a participant's CSA differs from the average CSA of their age and sex). Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)\]/S); Ln=natural logarithm; M=age- or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Bone Structure Using Peripheral Quantitative Computed Tomography (pQCT) After 1 Year and 2 Years: Total Cross-sectional Area (CSA) Month 12 (n=2, 5)	0.375 z-score Standard Error 0.9345	0.239 z-score Standard Error 0.5537
Change From Baseline in Bone Structure Using Peripheral Quantitative Computed Tomography (pQCT) After 1 Year and 2 Years: Total Cross-sectional Area (CSA) Month 24 (n=2, 6)	0.243 z-score Standard Error 0.3694	-0.049 z-score Standard Error 0.1955

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards; (n)=number of participants from FAS with evaluable pQCT data for somatropin and control arm groups, respectively.

Bone structure Muscle CSA measured as millimeters squared (mm2). CSA (proximal radius) SDS (number of standard deviations a participant's CSA differs from the average CSA of their age and sex). Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)\]/S); Ln=natural logarithm; M=age- or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Bone Structure Using pQCT After 1 Year and 2 Years: Muscle Cross-sectional Area (CSA) Month 12 (n=2, 6)	2.084 z-score Standard Error 0.3628	-0.227 z-score Standard Error 0.1688
Change From Baseline in Bone Structure Using pQCT After 1 Year and 2 Years: Muscle Cross-sectional Area (CSA) Month 24 (n=2, 6)	2.402 z-score Standard Error 0.5221	0.776 z-score Standard Error 0.2428

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards. Cortical thickness was not analyzed as planned.

Cortical Thickness measured as millimeters (mm). CT (proximal radius) SDS (number of standard deviations a participant's CT differs from the average CT of their age and sex). Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)\]/S); Ln=natural logarithm; M=age- or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards. Marrow Area was not analyzed as planned.

Marrow Area measured as millimeters squared (mm2). MA (proximal radius) SDS (number of standard deviations a participant's MA differs from the average MA of their age and sex). Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)\]/S); Ln=natural logarithm; M=age- or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards; (n)=number of participants from FAS with evaluable pQCT data for somatropin and control arm groups, respectively.

Bone stability expressed as polar SSI in cubic millimeters (mm3). SSI (proximal radius) SDS (number of standard deviations a participant's SSI differs from the average SSI of their age and sex). Baseline and post-baseline SDS values transformed to age and sex specific z-score (Ln(test result/M)\]/S); Ln=natural logarithm; M=age- or height-) and sex-specific mean value; S=age-(or height-) and sex-specific coefficient of variation) then change from baseline is calculated. Positive values are above the average for participant's age and sex; negative values are below the average.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Bone Stability Using pQCT After 1 Year and After 2 Years: Strength-strain Index (SSI) Month 12 (n=2, 6)	0.648 z-score Standard Error 0.4224	0.088 z-score Standard Error 0.2243
Change From Baseline in Bone Stability Using pQCT After 1 Year and After 2 Years: Strength-strain Index (SSI) Month 24 (n=2, 6)	0.477 z-score Standard Error 0.3925	0.363 z-score Standard Error 0.2084

SECONDARY outcome

Timeframe: Baseline, Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards; (n)=number of participants ≥6 years of age with evaluable data at observation for Somatropin and Control Arm, respectively. SDS reference values used were for the right hand but the hand grip strength measured for this study was for the dominant hand (may not have been the right hand).

Muscle strength determined by measuring grip force (kilograms) using hand grip dynamometer for participants ≥6 years of age. Baseline and post-baseline SDS values transformed to age and sex specific z-score. Change in hand grip calculated as SDS where SDS = hand grip minus mean (age- and sex-matched reference) divided by SD (age- and sex-matched reference). Positive values are above the average for participant's age and sex; negative values are below the average.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Change From Baseline in Muscle Strength: Hand Grip SDS After 1 Year and After 2 Years Month 12 (n=7, 5)	0.37 z-score Standard Error 0.268	0.28 z-score Standard Error 0.318
Change From Baseline in Muscle Strength: Hand Grip SDS After 1 Year and After 2 Years Month 24 (n=7, 6)	1.14 z-score Standard Error 0.218	0.92 z-score Standard Error 0.236

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: FAS

Insulin sensitivity calculated as incidence of pathological glucose intolerance assessed prior to randomization (Screening Day -3 to Baseline Day 0) and at final visit (final visit: Somatropin treatment group=Month 24). Pathological glucose intolerance (oral glucose tolerance test) measured as venous (blood or plasma) with range minimum 120 milligrams per deciliter (mg/dL) to \>140 mg/dL; capillary (blood) with range minimum 120 mg/dL to \>120 mg/dL; or method not known with range minimum 120 mg/dL to \>120 mg/dL.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Number of Participants With Change in Insulin Sensitivity: Somatropin Baseline: tolerant	18 participants	—
Number of Participants With Change in Insulin Sensitivity: Somatropin Baseline: intolerant	0 participants	—
Number of Participants With Change in Insulin Sensitivity: Somatropin Month 24: tolerant	16 participants	—
Number of Participants With Change in Insulin Sensitivity: Somatropin Month 24: intolerant	0 participants	—

SECONDARY outcome

Timeframe: Baseline, Month 36

Population: FAS; Control group received Somatropin from Month 12 onwards.

Insulin sensitivity calculated as incidence of pathological glucose intolerance assessed prior to randomization (Screening Day -3 to Baseline Day 0) and at final visit (final visit: Control Arm=Month 36). Pathological glucose intolerance (oral glucose tolerance test) measured as venous (blood or plasma) with range minimum 120 milligrams per deciliter (mg/dL) to \>140 mg/dL; capillary (blood) with range minimum 120 mg/dL to \>120 mg/dL; or method not known with range minimum 120 mg/dL to \>120 mg/dL.

Outcome measures

Outcome measures
Measure	Somatropin n=15 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Number of Participants With Change in Insulin Sensitivity: Control Arm Baseline: tolerant	14 participants	—
Number of Participants With Change in Insulin Sensitivity: Control Arm Baseline: intolerant	1 participants	—
Number of Participants With Change in Insulin Sensitivity: Control Arm Month 36: tolerant	11 participants	—
Number of Participants With Change in Insulin Sensitivity: Control Arm Month 36: intolerant	2 participants	—

SECONDARY outcome

Timeframe: Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards. Data for Month 36 (applicable only to the Control Arm) is reported in a separate outcome measure.

Growth curve comparison with height SDS in centimeters as the dependent variable; SDS = height minus mean (age-and sex-matched reference) divided by SD (age and sex-matched reference).

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Growth Curve Comparison Based on Height SDS Month 12	-2.260 centimeters Standard Error 0.0735	-3.259 centimeters Standard Error 0.0802
Growth Curve Comparison Based on Height SDS Month 24	-1.638 centimeters Standard Error 0.1016	-2.327 centimeters Standard Error 0.1122

SECONDARY outcome

Timeframe: Month 36

Population: FAS; Control group received Somatropin from Month 12 onwards. N=number of subjects with evaluable data at observation. Month 36 visit not applicable to Somatropin treatment group.

Growth curve comparison with height SDS in centimeters as the dependent variable; SDS = height minus mean (age-and sex-matched reference) divided by SD (age and sex-matched reference). Control Arm final visit=Month 36.

Outcome measures

Outcome measures
Measure	Somatropin n=14 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Growth Curve Comparison Based on Height SDS: Control Arm	-1.794 centimeters Standard Error 0.1318	—

SECONDARY outcome

Timeframe: Month 12, Month 24

Population: FAS; Control group received Somatropin from Month 12 onwards. Data for Month 36 (applicable only to the Control Arm) is reported in a separate outcome measure.

Growth curve comparison with height in centimeters as the dependent variable.

Outcome measures

Outcome measures
Measure	Somatropin n=18 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 Participants The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Growth Curve Comparison Based on Height Month 24	123.351 centimeters Standard Error 0.4830	119.788 centimeters Standard Error 0.5255
Growth Curve Comparison Based on Height Month 12	114.228 centimeters Standard Error 0.3330	109.644 centimeters Standard Error 0.3733

SECONDARY outcome

Timeframe: Month 36

Population: FAS; Control group received Somatropin from Month 12 onwards. N=number of subjects with evaluable data at observation. Month 36 visit not applicable to Somatropin treatment group.

Growth curve comparison with height in centimeters as the dependent variable.

Outcome measures

Outcome measures
Measure	Somatropin n=14 Participants The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
Growth Curve Comparison Based on Height: Control Arm	128.049 centimeters Standard Error 0.7821	—

Adverse Events

Somatropin

Serious events: 5 serious events

Other events: 13 other events

Deaths: 0 deaths

Control Arm

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Somatropin n=18 participants at risk The children were randomized into a treated group receiving 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. (mg=milligrams, kg=kilograms)	Control Arm n=15 participants at risk The children were randomized into control group and after 1 year underwent Growth Hormone (GH) therapy, with 0.068 mg/kg/day (0.48mg/kg/week) subcutaneous somatropin according to exact body weight specific calculation. Dose adjustments were made at 6 month intervals. mg=milligram, kg=kilogram.
General disorders Pyrexia	5.6% 1/18 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.00% 0/15 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Acute tonsillitis	5.6% 1/18 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.00% 0/15 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Bronchitis viral	5.6% 1/18 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.00% 0/15 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Bronchopneumonia	5.6% 1/18 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.00% 0/15 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Ear infection	5.6% 1/18 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.00% 0/15 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Infections and infestations Tonsillitis	11.1% 2/18 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.00% 0/15 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Facial palsy	0.00% 0/18 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	6.7% 1/15 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Nervous system disorders Febrile convulsion	5.6% 1/18 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.00% 0/15 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.
Respiratory, thoracic and mediastinal disorders Asthma	5.6% 1/18 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.	0.00% 0/15 Safety population=all participants who received at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.

Other adverse events

Additional Information

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Results disclosure agreements

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