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Genotropin Treatment in Short Prepubertal Children With Intra-Uterine Growth Retardation

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ClinicalTrials.gov Identifier: NCT01073605
Recruitment Status : Completed
First Posted : February 23, 2010
Results First Posted : August 31, 2010
Last Update Posted : November 18, 2010
Sponsor:
Information provided by:
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Growth Disorders
Intrauterine Growth Retardation
Intervention Drug: Genotonorm
Enrollment 208
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description Subjects received 0.7 international unit (IU)/kilogram (kg)/week (0.03 milligram [mg]/kg/day) of Genotonorm growth hormone (GH) as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached. Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached. Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Period Title: Overall Study
Started 68 71 69
Received Treatment 68 70 68
Completed 6 [1] 4 [1] 8 [1]
Not Completed 62 67 61
Reason Not Completed
Ongoing at Cutoff Date             1             1             0
Adverse Event             2             1             0
Lost to Follow-up             3             4             9
Other             25             21             29
Withdrawal by Subject             31             39             22
Randomized But Not Treated             0             1             1
[1]
Corresponds to follow-up until final height
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment) Total
Hide Arm/Group Description Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached. Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached. Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached. Total of all reporting groups
Overall Number of Baseline Participants 68 70 68 206
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 68 participants 70 participants 68 participants 206 participants
< 4 years 15 8 6 29
4 - 8 years 29 32 29 90
8 - 12 years 23 30 33 86
>= 12 years 1 0 0 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 68 participants 70 participants 68 participants 206 participants
Female
25
  36.8%
31
  44.3%
39
  57.4%
95
  46.1%
Male
43
  63.2%
39
  55.7%
29
  42.6%
111
  53.9%
1.Primary Outcome
Title Change From Baseline in Annual Growth Rate Measured at 2 Years Following Treatment With Genotonorm
Hide Description Annual growth rate was expressed as height velocity (centimeter [cm]/year). This was derived by substracting annual growth rate at Baseline from 2-year value. (Annual growth rate was calculated each year and rescaled to 1 year if the interval between x and x-1 was not 365 days, as long as a subject remains in the study): ANGRYx = (Height Yx – Height Y{x-1}) / {(Date of Yx – Date of Y{x-1}) /365.25}
Time Frame Baseline, 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least 1 study dose of Genotonorm were included in the Full Analysis Set (FAS). Number of Participants Analyzed = number of subjects with change in annual growth rate at 2 years.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 47 37 40
Mean (Standard Deviation)
Unit of Measure: cm/year
3.07  (2.21) 3.97  (1.72) 2.84  (1.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Continuous Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02922
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.74299
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Genotonorm 1.4 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00467
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Annual Growth Rate Standard Deviation Score (SDS)
Hide Description Calculated using Sempe reference means and standard deviations for growth rate according to age and sex. Standardization was performed for chronological age.
Time Frame Baseline, 1 to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Number of Participants Analyzed = number of subjects with evaluable data at Baseline. n = number of subjects with evaluable data at each time point. Data beyond 6 years are not reported due to the low proportion of subjects followed up beyond 6 years.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 50 42 43
Mean (Standard Deviation)
Unit of Measure: SDS
Baseline (n=50, 42, 43) -2.72  (1.83) -2.58  (1.39) -2.75  (1.73)
1 year (n=57, 55, 59) 2.14  (1.52) 3.97  (2.26) 1.71  (1.51)
2 years (n=53, 49, 56) 0.77  (1.57) 2.00  (1.73) 0.67  (1.22)
3 years (n=39, 34, 41) 0.36  (1.14) 1.35  (1.78) 0.31  (1.12)
4 years (n=21, 18, 27) 0.13  (1.55) 0.61  (1.20) 0.34  (1.20)
5 years (n=12, 10, 20) 0.18  (1.24) 0.09  (0.88) -0.02  (1.46)
6 years (n=11, 7, 19) 0.90  (1.92) 0.59  (1.61) 0.05  (1.20)
3.Secondary Outcome
Title Change From Baseline in Annual Growth Rate SDS
Hide Description Calculated corresponding to the gender and chronological age by substracting annual growth rate SDS at Baseline from annual growth rate SDS at each year.
Time Frame Baseline, 1 to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Number of Participants Analyzed = number of subjects with evaluable data at 1 year. n = number of subjects with evaluable data at each time point.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 49 42 42
Mean (Standard Deviation)
Unit of Measure: SDS
1 year (n=49, 42, 42) 4.81  (2.27) 6.56  (2.55) 4.37  (2.16)
2 years (n=47, 37, 40) 3.51  (2.50) 4.53  (1.89) 3.37  (2.33)
3 years (n=34, 25, 32) 3.31  (2.06) 3.80  (2.20) 3.17  (1.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Continuous Treatment)
Comments 1 year
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00125
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments 1 year
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25995
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Genotonorm 1.4 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments 1 year
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00008
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Continuous Treatment)
Comments 2 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03273
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments 2 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68581
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Genotonorm 1.4 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments 2 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00530
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Continuous Treatment)
Comments 3 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57556
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments 3 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.63956
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Genotonorm 1.4 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments 3 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16421
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title Height (cm)
Hide Description Performed by use of a wallmounted device (eg, Harpenden Stadiometer). Each subject was measured 3 times and the mean of these measurements was recorded as the present height. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls.
Time Frame Baseline, 1 to 6 years, final height
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Number of Participants Analyzed = number of subjects with evaluable data at Baseline. n = number of subjects with evaluable data at each time point. Data beyond 6 years are not reported due to the low proportion of subjects followed up beyond 6 years.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 58 56 60
Mean (Standard Deviation)
Unit of Measure: cm
Baseline (n=58, 56, 60) 105.22  (15.04) 107.06  (12.29) 106.44  (12.04)
1 year (n=57, 55, 59) 113.38  (15.09) 116.31  (12.24) 113.71  (12.01)
2 years (n=53, 49, 56) 119.67  (15.18) 124.11  (13.02) 120.64  (12.34)
3 years (n=39, 34, 41) 123.92  (15.08) 131.75  (13.76) 125.39  (12.52)
4 years (n=21, 18, 27) 124.67  (13.14) 132.30  (13.23) 127.59  (11.51)
5 years (n=12, 10, 21) 126.73  (10.01) 131.01  (9.26) 129.98  (9.93)
6 years (n=11, 7, 20) 133.29  (10.46) 138.84  (8.69) 135.45  (10.10)
Final height (n=17, 12, 22) 146.86  (11.26) 151.98  (6.52) 149.13  (9.07)
5.Secondary Outcome
Title Change From Baseline in Height (cm)
Hide Description Calculated by substracting height at Baseline from height at each year. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls.
Time Frame Baseline, 1 to 6 years, final height
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Number of Participants Analyzed = number of subjects with evaluable data at Baseline. n = number of subjects with evaluable data at Baseline and each time point. Data beyond 6 years are not reported due to the low proportion of subjects followed up beyond 6 years.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 58 56 60
Mean (Standard Deviation)
Unit of Measure: cm
1 year (n=57, 55, 59) 8.21  (1.38) 9.21  (1.45) 7.33  (1.32)
2 years (n=53, 49, 56) 14.77  (2.45) 17.01  (2.21) 13.92  (2.03)
3 years (n=39, 34, 41) 20.62  (3.00) 24.49  (3.04) 20.14  (2.78)
4 years (n=21, 18, 27) 26.36  (4.37) 30.77  (3.43) 25.83  (3.26)
5 years (n=12, 10, 21) 32.23  (5.92) 35.70  (4.27) 32.16  (3.81)
6 years (n=11, 7, 20) 38.20  (6.66) 44.03  (3.09) 38.01  (4.82)
Final height (n=17, 12, 22) 45.39  (13.08) 45.30  (13.72) 40.93  (9.22)
6.Secondary Outcome
Title Height (SDS)
Hide Description Calculated using Sempe reference means and standard deviations for height. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls.
Time Frame Baseline, 1 to 6 years, final height
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Number of Participants Analyzed = number of subjects with evaluable data at Baseline. n = number of subjects with evaluable data at each time point. Data beyond 6 years are not reported due to the low proportion of subjects followed up beyond 6 years.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 58 56 60
Mean (Standard Deviation)
Unit of Measure: SDS
Baseline (n=58, 56, 60) -3.16  (0.52) -3.07  (0.46) -3.21  (0.65)
1 year (n=57, 55, 59) -2.49  (0.54) -2.17  (0.50) -2.68  (0.69)
2 years (n=53, 49, 56) -2.21  (0.66) -1.68  (0.52) -2.38  (0.75)
3 years (n=39, 34, 41) -2.17  (0.70) -1.38  (0.57) -2.24  (0.90)
4 years (n=21, 18, 27) -2.16  (1.03) -1.16  (0.73) -2.09  (0.96)
5 years (n=12, 10, 21) -1.95  (1.26) -1.15  (0.83) -1.96  (1.10)
6 years (n=11, 7, 19) -1.80  (1.28) -0.67  (0.66) -1.93  (1.18)
Final height (n=14, 9, 18) -2.06  (0.76) -1.97  (0.95) -2.29  (1.35)
7.Secondary Outcome
Title Change From Baseline in Height (SDS)
Hide Description Calculated by substracting height SDS at Baseline from height SDS at each year. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls.
Time Frame Baseline, 1 to 6 years, final height
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Number of Participants Analyzed = number of subjects with evaluable data at Baseline. n = number of subjects with evaluable data at Baseline and each time point. Data beyond 6 years are not reported due to the low proportion of subjects followed up beyond 6 years.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 58 56 60
Mean (Standard Deviation)
Unit of Measure: SDS
1 year (n=57, 55, 59) 0.67  (0.28) 0.88  (0.30) 0.53  (0.28)
2 years (n=53, 49, 56) 0.94  (0.45) 1.40  (0.43) 0.84  (0.37)
3 years (n=39, 34, 41) 1.06  (0.54) 1.70  (0.54) 0.99  (0.51)
4 years (n=21, 18, 27) 1.20  (0.81) 1.98  (0.69) 1.21  (0.54)
5 years (n=12, 10, 21) 1.37  (1.12) 2.03  (0.87) 1.46  (0.69)
6 years (n=11, 7, 19) 1.54  (1.12) 2.60  (0.66) 1.54  (0.86)
Final height (n=14, 9, 18) 1.00  (0.53) 0.97  (0.95) 0.86  (1.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Continuous Treatment)
Comments 3 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments 3 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58324
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Genotonorm 1.4 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments 3 years
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-values for the 3 treatment comparisons should be interpreted in line with the Bonferroni stepwise (Holm) testing procedure, to maintain the Type 1 error at p=0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Body Mass Index (BMI)
Hide Description BMI was calculated by weight divided by height squared.
Time Frame Baseline, 1 to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Number of Participants Analyzed = number of subjects with evaluable data at Baseline. n = number of subjects with evaluable data at each time point. Data beyond 6 years are not reported due to the low proportion of subjects followed up beyond 6 years.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 58 56 60
Mean (Standard Deviation)
Unit of Measure: kg/m^2
Baseline (n=58, 56, 60) 14.74  (1.48) 15.14  (1.76) 14.59  (1.51)
1 year (n=56, 55, 59) 14.82  (1.52) 15.44  (1.94) 14.87  (1.76)
2 years (n=53, 49, 56) 15.33  (1.78) 15.92  (2.15) 15.29  (2.00)
3 years (n=39, 34, 41) 15.59  (2.02) 16.65  (2.92) 15.58  (2.11)
4 years (n=21, 18, 27) 15.32  (1.56) 17.03  (3.70) 15.80  (2.37)
5 years (n=12, 10, 21) 15.80  (1.57) 16.25  (1.70) 16.69  (3.92)
6 years (n=11, 7, 20) 16.21  (1.46) 16.34  (1.80) 17.28  (4.21)
9.Secondary Outcome
Title Weight
Hide Description [Not Specified]
Time Frame Baseline, 1 to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS. Number of Participants Analyzed = number of subjects with evaluable data at Baseline. n = number of subjects with evaluable data at each time point. Data beyond 6 years are not reported due to the low proportion of subjects followed up beyond 6 years.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 58 56 60
Mean (Standard Deviation)
Unit of Measure: kg
Baseline (n=58, 56, 60) 16.77  (5.43) 17.70  (5.12) 16.79  (4.35)
1 year (n=56, 55, 59) 19.71  (6.28) 21.29  (6.04) 19.56  (5.17)
2 years (n=53, 49, 56) 22.66  (7.62) 25.08  (7.43) 22.64  (6.05)
3 years (n=39, 34, 41) 24.77  (8.80) 29.61  (9.62) 24.98  (7.05)
4 years (n=21, 18, 27) 24.30  (7.01) 30.56  (10.42) 26.28  (7.94)
5 years (n=12, 10, 21) 25.74  (6.22) 28.07  (5.22) 28.52  (8.96)
6 years (n=11, 7, 21) 29.13  (6.42) 31.94  (7.28) 32.30  (10.32)
10.Secondary Outcome
Title Change From Baseline in Bone Age
Hide Description Bone age was determined by the Greulich-Pyle method. Calculated by substracting bone age at Baseline from bone age at each year
Time Frame Baseline, 1 to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population = all subjects who received at least 1 study dose of GH. Number of Participants Analyzed = number of subjects with evaluable data at Baseline. n = number of subjects with evaluable data at Baseline and each time point.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 61 62 61
Mean (Standard Deviation)
Unit of Measure: Years
1 year (n=53, 60, 56) 1.17  (0.51) 1.27  (0.72) 1.25  (0.54)
2 years (n=52, 51, 49) 2.40  (0.90) 2.50  (1.08) 2.58  (0.97)
3 years (n=41, 39, 35) 3.53  (1.22) 4.06  (1.05) 3.67  (0.97)
11.Secondary Outcome
Title Change From Baseline in Bone Age/Change From Baseline in Chronological Age Ratio
Hide Description Bone age was determined by the Greulich-Pyle method. Chronological Age (years) was calculated as: (Date minus Date of Birth) divided by 365.25. Chronological Age used was the age at the date that the corresponding Bone Age X-ray was performed. Ratio was calculated by change from Baseline in bone age divided by change from Baseline in chronological age.
Time Frame 1 to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population = all subjects who received at least 1 study dose of GH. Number of Participants Analyzed = number of subjects with evaluable data at 1 year. n = number of subjects with evaluable data at each time point.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 53 60 56
Mean (Standard Deviation)
Unit of Measure: ratio
1 year (n=53, 60, 56) 0.96  (0.41) 1.07  (0.62) 1.06  (0.45)
2 years (n=51, 51, 49) 1.06  (0.41) 1.14  (0.50) 1.18  (0.44)
3 years (n=35, 37, 35) 1.09  (0.39) 1.26  (0.32) 1.14  (0.29)
12.Secondary Outcome
Title Chronological Age at Onset of Puberty
Hide Description Chronological age (years) at first study visit with onset of puberty = (Date of study visit minus Date of Birth) divided by 365.25.
Time Frame Onset of puberty
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population. Number of participants analyzed = number of subjects who started puberty by the end of the study.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 30 35 45
Mean (Standard Deviation)
Unit of Measure: Years
11.88  (2.22) 11.12  (1.74) 11.58  (1.42)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Continuous Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0681
Comments There is no adjustment for multiplicity of treatment comparisons.
Method ANCOVA
Comments The Analysis of Covariance took into account the patient covariates age and gender.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
-0.05 to 1.39
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Genotonorm 0.7 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8971
Comments There is no adjustment for multiplicity of treatment comparisons.
Method ANCOVA
Comments The Analysis of Covariance took into account the patient covariates age and gender.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.65 to 0.74
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Genotonorm 1.4 (Continuous Treatment), Genotonorm 1.4 (Intermittent Treatment)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0583
Comments There is no adjustment for multiplicity of treatment comparisons.
Method ANCOVA
Comments The Analysis of Covariance took into account the patient covariates age and gender.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-1.27 to 0.02
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Number of Subjects Reaching Puberty
Hide Description The defined criteria for reaching puberty were: boy=if right or left testes volume ≥4 ml; girl=if breast development ≥2. Tanner Adolescent Pubertal Staging Questionnaire documents the stage of development of secondary sexual characteristics rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Onset of puberty was defined as the visit where the data recorded first met the above criteria for starting puberty.
Time Frame Baseline, 1 to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population. Number of Participants Analyzed = number of subjects with evaluable data at Baseline. Data beyond 6 years are not reported due to the low proportion of subjects followed up beyond 6 years. Started = started puberty; Not Started = not started puberty yet as per Tanner scale.
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description:
Subjects received 0.7 IU/kg/week (0.03 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
Overall Number of Participants Analyzed 68 70 68
Measure Type: Number
Unit of Measure: participants
Baseline (Female, Not Started) 25 31 39
Baseline (Male, Not Started) 43 39 29
1 year (Female, Not Started) 24 27 37
1 year (Female, Started) 1 3 2
1 year (Male, Not Started) 36 35 27
1 year (Male, Started) 4 3 1
2 years (Female, Not Started) 20 20 31
2 years (Female, Started) 3 7 6
2 years (Male, Not Started) 31 28 20
2 years (Male, Started) 9 7 6
3 years (Female, Not Started) 16 10 16
3 years (Female, Started) 3 9 11
3 years (Male, Not Started) 19 15 9
3 years (Male, Started) 6 7 4
4 years (Female, Not Started) 10 7 10
4 years (Female, Started) 2 5 7
4 years (Male, Not Started) 10 5 7
4 years (Male, Started) 1 2 3
5 years (Female, Not Started) 5 4 5
5 years (Female, Started) 2 3 10
5 years (Male, Not Started) 6 6 4
5 years (Male, Started) 2 1 1
6 years (Female, Not Started) 3 3 3
6 years (Female, Started) 3 2 12
6 years (Male, Not Started) 5 4 1
6 years (Male, Started) 3 1 4
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Hide Arm/Group Description Subjects received 0.7 international unit (IU)/kilogram (kg)/week (0.03 milligram [mg]/kg/day) of Genotonorm growth hormone (GH) as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached. Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as a continuous treatment. Treatment was allowed to be taken until final height of the subject had been reached. Subjects received 1.4 IU/kg/week (0.06 mg/kg/day) of the growth hormone Genotonorm as an intermittent treatment. Treatment was allowed to be taken until final height of the subject had been reached.
All-Cause Mortality
Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/68 (0.00%)   4/70 (5.71%)   3/68 (4.41%) 
Surgical and medical procedures       
Tonsillectomy  1  0/68 (0.00%)  4/70 (5.71%)  3/68 (4.41%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Genotonorm 0.7 (Continuous Treatment) Genotonorm 1.4 (Continuous Treatment) Genotonorm 1.4 (Intermittent Treatment)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   40/68 (58.82%)   42/70 (60.00%)   35/68 (51.47%) 
Gastrointestinal disorders       
Abdominal pain  1  4/68 (5.88%)  3/70 (4.29%)  4/68 (5.88%) 
Diarrhoea  1  5/68 (7.35%)  0/70 (0.00%)  4/68 (5.88%) 
General disorders       
Pyrexia  1  4/68 (5.88%)  3/70 (4.29%)  3/68 (4.41%) 
Infections and infestations       
Bronchitis  1  13/68 (19.12%)  9/70 (12.86%)  17/68 (25.00%) 
Ear infection  1  15/68 (22.06%)  15/70 (21.43%)  9/68 (13.24%) 
Fungal infection  1  4/68 (5.88%)  1/70 (1.43%)  0/68 (0.00%) 
Gastroenteritis  1  4/68 (5.88%)  8/70 (11.43%)  11/68 (16.18%) 
Influenza  1  6/68 (8.82%)  9/70 (12.86%)  7/68 (10.29%) 
Nasopharyngitis  1  16/68 (23.53%)  16/70 (22.86%)  11/68 (16.18%) 
Pharyngitis  1  2/68 (2.94%)  6/70 (8.57%)  7/68 (10.29%) 
Rhinitis  1  4/68 (5.88%)  2/70 (2.86%)  6/68 (8.82%) 
Tracheitis  1  3/68 (4.41%)  5/70 (7.14%)  2/68 (2.94%) 
Upper respiratory tract infection  1  19/68 (27.94%)  19/70 (27.14%)  12/68 (17.65%) 
Varicella  1  8/68 (11.76%)  6/70 (8.57%)  1/68 (1.47%) 
Musculoskeletal and connective tissue disorders       
Scoliosis  1  2/68 (2.94%)  4/70 (5.71%)  0/68 (0.00%) 
Nervous system disorders       
Convulsion  1  0/68 (0.00%)  4/70 (5.71%)  0/68 (0.00%) 
Headache  1  2/68 (2.94%)  5/70 (7.14%)  3/68 (4.41%) 
Respiratory, thoracic and mediastinal disorders       
Asthma  1  5/68 (7.35%)  3/70 (4.29%)  3/68 (4.41%) 
Cough  1  1/68 (1.47%)  3/70 (4.29%)  5/68 (7.35%) 
Skin and subcutaneous tissue disorders       
Eczema  1  4/68 (5.88%)  1/70 (1.43%)  1/68 (1.47%) 
Urticaria  1  4/68 (5.88%)  0/70 (0.00%)  1/68 (1.47%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT01073605     History of Changes
Other Study ID Numbers: 93-8122-001
A6281186, CTN 93-8122-001
First Submitted: February 22, 2010
First Posted: February 23, 2010
Results First Submitted: May 6, 2010
Results First Posted: August 31, 2010
Last Update Posted: November 18, 2010