Trial Outcomes & Findings for Genotropin Treatment in Short Prepubertal Children With Intra-Uterine Growth Retardation (NCT NCT01073605)

Last Updated: 2010-11-18

Results Overview

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}

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

208 participants

Primary outcome timeframe

Baseline, 2 years

Results posted on

2010-11-18

Participant Flow

Participant milestones

Participant milestones
Measure	Genotonorm 0.7 (Continuous Treatment) 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.	Genotonorm 1.4 (Continuous Treatment) 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.	Genotonorm 1.4 (Intermittent Treatment) 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 Study STARTED	68	71	69
Overall Study Received Treatment	68	70	68
Overall Study COMPLETED	6	4	8
Overall Study NOT COMPLETED	62	67	61

Reasons for withdrawal

Reasons for withdrawal
Measure	Genotonorm 0.7 (Continuous Treatment) 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.	Genotonorm 1.4 (Continuous Treatment) 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.	Genotonorm 1.4 (Intermittent Treatment) 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 Study Ongoing at Cutoff Date	1	1	0
Overall Study Adverse Event	2	1	0
Overall Study Lost to Follow-up	3	4	9
Overall Study Other	25	21	29
Overall Study Withdrawal by Subject	31	39	22
Overall Study Randomized But Not Treated	0	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Genotonorm 0.7 (Continuous Treatment) n=68 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=70 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=68 Participants 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 n=206 Participants Total of all reporting groups
Age, Customized < 4 years	15 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	29 Participants n=4 Participants
Age, Customized 4 - 8 years	29 Participants n=5 Participants	32 Participants n=7 Participants	29 Participants n=5 Participants	90 Participants n=4 Participants
Age, Customized 8 - 12 years	23 Participants n=5 Participants	30 Participants n=7 Participants	33 Participants n=5 Participants	86 Participants n=4 Participants
Age, Customized >= 12 years	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	31 Participants n=7 Participants	39 Participants n=5 Participants	95 Participants n=4 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	39 Participants n=7 Participants	29 Participants n=5 Participants	111 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, 2 years

Population: 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.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=47 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=37 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=40 Participants 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.
Change From Baseline in Annual Growth Rate Measured at 2 Years Following Treatment With Genotonorm	3.07 cm/year Standard Deviation 2.21	3.97 cm/year Standard Deviation 1.72	2.84 cm/year Standard Deviation 1.71

SECONDARY outcome

Timeframe: Baseline, 1 to 6 years

Population: 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.

Calculated using Sempe reference means and standard deviations for growth rate according to age and sex. Standardization was performed for chronological age.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=50 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=42 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=43 Participants 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.
Annual Growth Rate Standard Deviation Score (SDS) Baseline (n=50, 42, 43)	-2.72 SDS Standard Deviation 1.83	-2.58 SDS Standard Deviation 1.39	-2.75 SDS Standard Deviation 1.73
Annual Growth Rate Standard Deviation Score (SDS) 1 year (n=57, 55, 59)	2.14 SDS Standard Deviation 1.52	3.97 SDS Standard Deviation 2.26	1.71 SDS Standard Deviation 1.51
Annual Growth Rate Standard Deviation Score (SDS) 2 years (n=53, 49, 56)	0.77 SDS Standard Deviation 1.57	2.00 SDS Standard Deviation 1.73	0.67 SDS Standard Deviation 1.22
Annual Growth Rate Standard Deviation Score (SDS) 3 years (n=39, 34, 41)	0.36 SDS Standard Deviation 1.14	1.35 SDS Standard Deviation 1.78	0.31 SDS Standard Deviation 1.12
Annual Growth Rate Standard Deviation Score (SDS) 4 years (n=21, 18, 27)	0.13 SDS Standard Deviation 1.55	0.61 SDS Standard Deviation 1.20	0.34 SDS Standard Deviation 1.20
Annual Growth Rate Standard Deviation Score (SDS) 5 years (n=12, 10, 20)	0.18 SDS Standard Deviation 1.24	0.09 SDS Standard Deviation 0.88	-0.02 SDS Standard Deviation 1.46
Annual Growth Rate Standard Deviation Score (SDS) 6 years (n=11, 7, 19)	0.90 SDS Standard Deviation 1.92	0.59 SDS Standard Deviation 1.61	0.05 SDS Standard Deviation 1.20

SECONDARY outcome

Timeframe: Baseline, 1 to 3 years

Population: 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.

Calculated corresponding to the gender and chronological age by substracting annual growth rate SDS at Baseline from annual growth rate SDS at each year.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=49 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=42 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=42 Participants 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.
Change From Baseline in Annual Growth Rate SDS 3 years (n=34, 25, 32)	3.31 SDS Standard Deviation 2.06	3.80 SDS Standard Deviation 2.20	3.17 SDS Standard Deviation 1.86
Change From Baseline in Annual Growth Rate SDS 1 year (n=49, 42, 42)	4.81 SDS Standard Deviation 2.27	6.56 SDS Standard Deviation 2.55	4.37 SDS Standard Deviation 2.16
Change From Baseline in Annual Growth Rate SDS 2 years (n=47, 37, 40)	3.51 SDS Standard Deviation 2.50	4.53 SDS Standard Deviation 1.89	3.37 SDS Standard Deviation 2.33

SECONDARY outcome

Timeframe: Baseline, 1 to 6 years, final height

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.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=58 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=56 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=60 Participants 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.
Height (cm) Baseline (n=58, 56, 60)	105.22 cm Standard Deviation 15.04	107.06 cm Standard Deviation 12.29	106.44 cm Standard Deviation 12.04
Height (cm) 1 year (n=57, 55, 59)	113.38 cm Standard Deviation 15.09	116.31 cm Standard Deviation 12.24	113.71 cm Standard Deviation 12.01
Height (cm) 2 years (n=53, 49, 56)	119.67 cm Standard Deviation 15.18	124.11 cm Standard Deviation 13.02	120.64 cm Standard Deviation 12.34
Height (cm) 3 years (n=39, 34, 41)	123.92 cm Standard Deviation 15.08	131.75 cm Standard Deviation 13.76	125.39 cm Standard Deviation 12.52
Height (cm) 4 years (n=21, 18, 27)	124.67 cm Standard Deviation 13.14	132.30 cm Standard Deviation 13.23	127.59 cm Standard Deviation 11.51
Height (cm) 5 years (n=12, 10, 21)	126.73 cm Standard Deviation 10.01	131.01 cm Standard Deviation 9.26	129.98 cm Standard Deviation 9.93
Height (cm) 6 years (n=11, 7, 20)	133.29 cm Standard Deviation 10.46	138.84 cm Standard Deviation 8.69	135.45 cm Standard Deviation 10.10
Height (cm) Final height (n=17, 12, 22)	146.86 cm Standard Deviation 11.26	151.98 cm Standard Deviation 6.52	149.13 cm Standard Deviation 9.07

SECONDARY outcome

Timeframe: Baseline, 1 to 6 years, final height

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=58 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=56 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=60 Participants 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.
Change From Baseline in Height (cm) 1 year (n=57, 55, 59)	8.21 cm Standard Deviation 1.38	9.21 cm Standard Deviation 1.45	7.33 cm Standard Deviation 1.32
Change From Baseline in Height (cm) 2 years (n=53, 49, 56)	14.77 cm Standard Deviation 2.45	17.01 cm Standard Deviation 2.21	13.92 cm Standard Deviation 2.03
Change From Baseline in Height (cm) 3 years (n=39, 34, 41)	20.62 cm Standard Deviation 3.00	24.49 cm Standard Deviation 3.04	20.14 cm Standard Deviation 2.78
Change From Baseline in Height (cm) 4 years (n=21, 18, 27)	26.36 cm Standard Deviation 4.37	30.77 cm Standard Deviation 3.43	25.83 cm Standard Deviation 3.26
Change From Baseline in Height (cm) 5 years (n=12, 10, 21)	32.23 cm Standard Deviation 5.92	35.70 cm Standard Deviation 4.27	32.16 cm Standard Deviation 3.81
Change From Baseline in Height (cm) 6 years (n=11, 7, 20)	38.20 cm Standard Deviation 6.66	44.03 cm Standard Deviation 3.09	38.01 cm Standard Deviation 4.82
Change From Baseline in Height (cm) Final height (n=17, 12, 22)	45.39 cm Standard Deviation 13.08	45.30 cm Standard Deviation 13.72	40.93 cm Standard Deviation 9.22

SECONDARY outcome

Timeframe: Baseline, 1 to 6 years, final height

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.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=58 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=56 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=60 Participants 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.
Height (SDS) Baseline (n=58, 56, 60)	-3.16 SDS Standard Deviation 0.52	-3.07 SDS Standard Deviation 0.46	-3.21 SDS Standard Deviation 0.65
Height (SDS) 1 year (n=57, 55, 59)	-2.49 SDS Standard Deviation 0.54	-2.17 SDS Standard Deviation 0.50	-2.68 SDS Standard Deviation 0.69
Height (SDS) 2 years (n=53, 49, 56)	-2.21 SDS Standard Deviation 0.66	-1.68 SDS Standard Deviation 0.52	-2.38 SDS Standard Deviation 0.75
Height (SDS) 3 years (n=39, 34, 41)	-2.17 SDS Standard Deviation 0.70	-1.38 SDS Standard Deviation 0.57	-2.24 SDS Standard Deviation 0.90
Height (SDS) 4 years (n=21, 18, 27)	-2.16 SDS Standard Deviation 1.03	-1.16 SDS Standard Deviation 0.73	-2.09 SDS Standard Deviation 0.96
Height (SDS) 5 years (n=12, 10, 21)	-1.95 SDS Standard Deviation 1.26	-1.15 SDS Standard Deviation 0.83	-1.96 SDS Standard Deviation 1.10
Height (SDS) 6 years (n=11, 7, 19)	-1.80 SDS Standard Deviation 1.28	-0.67 SDS Standard Deviation 0.66	-1.93 SDS Standard Deviation 1.18
Height (SDS) Final height (n=14, 9, 18)	-2.06 SDS Standard Deviation 0.76	-1.97 SDS Standard Deviation 0.95	-2.29 SDS Standard Deviation 1.35

SECONDARY outcome

Timeframe: Baseline, 1 to 6 years, final height

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.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=58 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=56 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=60 Participants 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.
Change From Baseline in Height (SDS) 1 year (n=57, 55, 59)	0.67 SDS Standard Deviation 0.28	0.88 SDS Standard Deviation 0.30	0.53 SDS Standard Deviation 0.28
Change From Baseline in Height (SDS) 2 years (n=53, 49, 56)	0.94 SDS Standard Deviation 0.45	1.40 SDS Standard Deviation 0.43	0.84 SDS Standard Deviation 0.37
Change From Baseline in Height (SDS) 3 years (n=39, 34, 41)	1.06 SDS Standard Deviation 0.54	1.70 SDS Standard Deviation 0.54	0.99 SDS Standard Deviation 0.51
Change From Baseline in Height (SDS) 4 years (n=21, 18, 27)	1.20 SDS Standard Deviation 0.81	1.98 SDS Standard Deviation 0.69	1.21 SDS Standard Deviation 0.54
Change From Baseline in Height (SDS) 5 years (n=12, 10, 21)	1.37 SDS Standard Deviation 1.12	2.03 SDS Standard Deviation 0.87	1.46 SDS Standard Deviation 0.69
Change From Baseline in Height (SDS) 6 years (n=11, 7, 19)	1.54 SDS Standard Deviation 1.12	2.60 SDS Standard Deviation 0.66	1.54 SDS Standard Deviation 0.86
Change From Baseline in Height (SDS) Final height (n=14, 9, 18)	1.00 SDS Standard Deviation 0.53	0.97 SDS Standard Deviation 0.95	0.86 SDS Standard Deviation 1.16

SECONDARY outcome

Timeframe: Baseline, 1 to 6 years

BMI was calculated by weight divided by height squared.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=58 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=56 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=60 Participants 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.
Body Mass Index (BMI) Baseline (n=58, 56, 60)	14.74 kg/m^2 Standard Deviation 1.48	15.14 kg/m^2 Standard Deviation 1.76	14.59 kg/m^2 Standard Deviation 1.51
Body Mass Index (BMI) 1 year (n=56, 55, 59)	14.82 kg/m^2 Standard Deviation 1.52	15.44 kg/m^2 Standard Deviation 1.94	14.87 kg/m^2 Standard Deviation 1.76
Body Mass Index (BMI) 2 years (n=53, 49, 56)	15.33 kg/m^2 Standard Deviation 1.78	15.92 kg/m^2 Standard Deviation 2.15	15.29 kg/m^2 Standard Deviation 2.00
Body Mass Index (BMI) 3 years (n=39, 34, 41)	15.59 kg/m^2 Standard Deviation 2.02	16.65 kg/m^2 Standard Deviation 2.92	15.58 kg/m^2 Standard Deviation 2.11
Body Mass Index (BMI) 4 years (n=21, 18, 27)	15.32 kg/m^2 Standard Deviation 1.56	17.03 kg/m^2 Standard Deviation 3.70	15.80 kg/m^2 Standard Deviation 2.37
Body Mass Index (BMI) 5 years (n=12, 10, 21)	15.80 kg/m^2 Standard Deviation 1.57	16.25 kg/m^2 Standard Deviation 1.70	16.69 kg/m^2 Standard Deviation 3.92
Body Mass Index (BMI) 6 years (n=11, 7, 20)	16.21 kg/m^2 Standard Deviation 1.46	16.34 kg/m^2 Standard Deviation 1.80	17.28 kg/m^2 Standard Deviation 4.21

SECONDARY outcome

Timeframe: Baseline, 1 to 6 years

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=58 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=56 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=60 Participants 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.
Weight Baseline (n=58, 56, 60)	16.77 kg Standard Deviation 5.43	17.70 kg Standard Deviation 5.12	16.79 kg Standard Deviation 4.35
Weight 1 year (n=56, 55, 59)	19.71 kg Standard Deviation 6.28	21.29 kg Standard Deviation 6.04	19.56 kg Standard Deviation 5.17
Weight 2 years (n=53, 49, 56)	22.66 kg Standard Deviation 7.62	25.08 kg Standard Deviation 7.43	22.64 kg Standard Deviation 6.05
Weight 3 years (n=39, 34, 41)	24.77 kg Standard Deviation 8.80	29.61 kg Standard Deviation 9.62	24.98 kg Standard Deviation 7.05
Weight 4 years (n=21, 18, 27)	24.30 kg Standard Deviation 7.01	30.56 kg Standard Deviation 10.42	26.28 kg Standard Deviation 7.94
Weight 5 years (n=12, 10, 21)	25.74 kg Standard Deviation 6.22	28.07 kg Standard Deviation 5.22	28.52 kg Standard Deviation 8.96
Weight 6 years (n=11, 7, 21)	29.13 kg Standard Deviation 6.42	31.94 kg Standard Deviation 7.28	32.30 kg Standard Deviation 10.32

SECONDARY outcome

Timeframe: Baseline, 1 to 3 years

Population: 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.

Bone age was determined by the Greulich-Pyle method. Calculated by substracting bone age at Baseline from bone age at each year

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=61 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=62 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=61 Participants 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.
Change From Baseline in Bone Age 1 year (n=53, 60, 56)	1.17 Years Standard Deviation 0.51	1.27 Years Standard Deviation 0.72	1.25 Years Standard Deviation 0.54
Change From Baseline in Bone Age 2 years (n=52, 51, 49)	2.40 Years Standard Deviation 0.90	2.50 Years Standard Deviation 1.08	2.58 Years Standard Deviation 0.97
Change From Baseline in Bone Age 3 years (n=41, 39, 35)	3.53 Years Standard Deviation 1.22	4.06 Years Standard Deviation 1.05	3.67 Years Standard Deviation 0.97

SECONDARY outcome

Timeframe: 1 to 3 years

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=53 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=60 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=56 Participants 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.
Change From Baseline in Bone Age/Change From Baseline in Chronological Age Ratio 1 year (n=53, 60, 56)	0.96 ratio Standard Deviation 0.41	1.07 ratio Standard Deviation 0.62	1.06 ratio Standard Deviation 0.45
Change From Baseline in Bone Age/Change From Baseline in Chronological Age Ratio 2 years (n=51, 51, 49)	1.06 ratio Standard Deviation 0.41	1.14 ratio Standard Deviation 0.50	1.18 ratio Standard Deviation 0.44
Change From Baseline in Bone Age/Change From Baseline in Chronological Age Ratio 3 years (n=35, 37, 35)	1.09 ratio Standard Deviation 0.39	1.26 ratio Standard Deviation 0.32	1.14 ratio Standard Deviation 0.29

SECONDARY outcome

Timeframe: Onset of puberty

Population: Safety population. Number of participants analyzed = number of subjects who started puberty by the end of the study.

Chronological age (years) at first study visit with onset of puberty = (Date of study visit minus Date of Birth) divided by 365.25.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=30 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=35 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=45 Participants 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.
Chronological Age at Onset of Puberty	11.88 Years Standard Deviation 2.22	11.12 Years Standard Deviation 1.74	11.58 Years Standard Deviation 1.42

SECONDARY outcome

Timeframe: Baseline, 1 to 6 years

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Genotonorm 0.7 (Continuous Treatment) n=68 Participants 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.	Genotonorm 1.4 (Continuous Treatment) n=70 Participants 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.	Genotonorm 1.4 (Intermittent Treatment) n=68 Participants 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.
Number of Subjects Reaching Puberty Baseline (Female, Not Started)	25 participants	31 participants	39 participants
Number of Subjects Reaching Puberty Baseline (Male, Not Started)	43 participants	39 participants	29 participants
Number of Subjects Reaching Puberty 1 year (Female, Not Started)	24 participants	27 participants	37 participants
Number of Subjects Reaching Puberty 1 year (Female, Started)	1 participants	3 participants	2 participants
Number of Subjects Reaching Puberty 1 year (Male, Not Started)	36 participants	35 participants	27 participants
Number of Subjects Reaching Puberty 1 year (Male, Started)	4 participants	3 participants	1 participants
Number of Subjects Reaching Puberty 2 years (Female, Not Started)	20 participants	20 participants	31 participants
Number of Subjects Reaching Puberty 2 years (Female, Started)	3 participants	7 participants	6 participants
Number of Subjects Reaching Puberty 2 years (Male, Not Started)	31 participants	28 participants	20 participants
Number of Subjects Reaching Puberty 2 years (Male, Started)	9 participants	7 participants	6 participants
Number of Subjects Reaching Puberty 3 years (Female, Not Started)	16 participants	10 participants	16 participants
Number of Subjects Reaching Puberty 3 years (Female, Started)	3 participants	9 participants	11 participants
Number of Subjects Reaching Puberty 3 years (Male, Not Started)	19 participants	15 participants	9 participants
Number of Subjects Reaching Puberty 3 years (Male, Started)	6 participants	7 participants	4 participants
Number of Subjects Reaching Puberty 4 years (Female, Not Started)	10 participants	7 participants	10 participants
Number of Subjects Reaching Puberty 4 years (Female, Started)	2 participants	5 participants	7 participants
Number of Subjects Reaching Puberty 4 years (Male, Not Started)	10 participants	5 participants	7 participants
Number of Subjects Reaching Puberty 4 years (Male, Started)	1 participants	2 participants	3 participants
Number of Subjects Reaching Puberty 5 years (Female, Not Started)	5 participants	4 participants	5 participants
Number of Subjects Reaching Puberty 5 years (Female, Started)	2 participants	3 participants	10 participants
Number of Subjects Reaching Puberty 5 years (Male, Not Started)	6 participants	6 participants	4 participants
Number of Subjects Reaching Puberty 5 years (Male, Started)	2 participants	1 participants	1 participants
Number of Subjects Reaching Puberty 6 years (Female, Not Started)	3 participants	3 participants	3 participants
Number of Subjects Reaching Puberty 6 years (Female, Started)	3 participants	2 participants	12 participants
Number of Subjects Reaching Puberty 6 years (Male, Not Started)	5 participants	4 participants	1 participants
Number of Subjects Reaching Puberty 6 years (Male, Started)	3 participants	1 participants	4 participants

Adverse Events

Genotonorm 0.7 (Continuous Treatment)

Serious events: 0 serious events

Other events: 40 other events

Deaths: 0 deaths

Genotonorm 1.4 (Continuous Treatment)

Serious events: 4 serious events

Other events: 42 other events

Deaths: 0 deaths

Genotonorm 1.4 (Intermittent Treatment)

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Genotonorm 0.7 (Continuous Treatment) n=68 participants at risk 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.	Genotonorm 1.4 (Continuous Treatment) n=70 participants at risk 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.	Genotonorm 1.4 (Intermittent Treatment) n=68 participants at risk 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.
Surgical and medical procedures Tonsillectomy	0.00% 0/68 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.	5.7% 4/70 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.	4.4% 3/68 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.

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Genotonorm 0.7 (Continuous Treatment) n=68 participants at risk 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.	Genotonorm 1.4 (Continuous Treatment) n=70 participants at risk 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.	Genotonorm 1.4 (Intermittent Treatment) n=68 participants at risk 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.
Gastrointestinal disorders Abdominal pain	5.9% 4/68 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.	4.3% 3/70 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.	5.9% 4/68 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.
Gastrointestinal disorders Diarrhoea	7.4% 5/68 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.	0.00% 0/70 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.	5.9% 4/68 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.
General disorders Pyrexia	5.9% 4/68 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.	4.3% 3/70 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.	4.4% 3/68 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.
Infections and infestations Bronchitis	19.1% 13/68 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.	12.9% 9/70 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.	25.0% 17/68 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.
Infections and infestations Ear infection	22.1% 15/68 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.	21.4% 15/70 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.	13.2% 9/68 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.
Infections and infestations Fungal infection	5.9% 4/68 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.	1.4% 1/70 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.	0.00% 0/68 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.
Infections and infestations Gastroenteritis	5.9% 4/68 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.	11.4% 8/70 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.	16.2% 11/68 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.
Infections and infestations Influenza	8.8% 6/68 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.	12.9% 9/70 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.	10.3% 7/68 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.
Infections and infestations Nasopharyngitis	23.5% 16/68 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.	22.9% 16/70 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.	16.2% 11/68 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.
Infections and infestations Pharyngitis	2.9% 2/68 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.	8.6% 6/70 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.	10.3% 7/68 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.
Infections and infestations Rhinitis	5.9% 4/68 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.	2.9% 2/70 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.	8.8% 6/68 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.
Infections and infestations Tracheitis	4.4% 3/68 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.	7.1% 5/70 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.	2.9% 2/68 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.
Infections and infestations Upper respiratory tract infection	27.9% 19/68 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.	27.1% 19/70 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.	17.6% 12/68 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.
Infections and infestations Varicella	11.8% 8/68 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.	8.6% 6/70 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.	1.5% 1/68 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.
Musculoskeletal and connective tissue disorders Scoliosis	2.9% 2/68 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.	5.7% 4/70 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.	0.00% 0/68 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.
Nervous system disorders Convulsion	0.00% 0/68 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.	5.7% 4/70 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.	0.00% 0/68 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.
Nervous system disorders Headache	2.9% 2/68 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.	7.1% 5/70 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.	4.4% 3/68 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.
Respiratory, thoracic and mediastinal disorders Asthma	7.4% 5/68 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.	4.3% 3/70 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.	4.4% 3/68 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.
Respiratory, thoracic and mediastinal disorders Cough	1.5% 1/68 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.	4.3% 3/70 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.	7.4% 5/68 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.
Skin and subcutaneous tissue disorders Eczema	5.9% 4/68 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.	1.4% 1/70 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.	1.5% 1/68 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.
Skin and subcutaneous tissue disorders Urticaria	5.9% 4/68 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.	0.00% 0/70 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.	1.5% 1/68 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.