rhGH and rhIGF-1 Combination Therapy in Children With Sho... | NCT00572156

ID	Type	Description	Link
2019-000843-29	EudraCT Number

Label	Type	Intervention Names
1. rhGH Alone	Active Comparator	Drug: NutropinAq® (Somatropin [rDNA origin])
2. Combination Dose	Experimental	Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
3. Combination Dose	Experimental	Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
4. Combination Dose	Experimental	Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])

Name	Type	Description	Arm Group Labels	Other Names
NutropinAq® (Somatropin [rDNA origin])	Drug	rhGH (Somatropin) 45µg/kg once daily injection	1. rhGH Alone

Measure	Description	Time Frame
Height Velocity		First year of treatment

Measure	Description	Time Frame
Height Velocity		Second, third and fourth year
Cumulative Change in Height Standard Deviation Score (SDS)	Height was measured standing and without shoes, and recorded as the mean of three measurements (the subject being repositioned each time) by the same observer using a Harpenden or other wall-mounted stadiometer which was to be calibrated prior to measurement of each subject and a calibration log kept. The SDS was calculated as: SDS=[(value /M)^L - 1] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)

Name	Affiliation	Role
Ipsen Medical Director	Ipsen (formerly Tercica, Inc.)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Ipsen		Brisbane	California	94005	United States

ID	Title	Description
FG000	45 rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): Recombinant Human Growth Hormone (rhGH) (Somatropin) 45µg/kg once daily injection
FG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and Recombinant Human Insulin-Like Growth Factor-1 (rhIGF-1) (Mecasermin) 50µg/kg once daily injections

ID	Title	Description
BG000	45 rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
BG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
BG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
BG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00026 BG00127 BG00227 BG00326 BG004106

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0009.2± 2.0 BG0018.4± 2.0 BG0029.0± 2.2 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0005 BG0015 BG002

Race

Number

participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG0002 BG0014 BG002

Height

Height was measured standing and without shoes, and recorded as the mean of three measurements (the subject being repositioned each time) by the same observer using a Harpenden or other wall-mounted stadiometer which was to be calibrated prior to measurement of each subject and a calibration log kept.

The SDS calculation and description is specified in baseline characteristic for parameter 'Weight'

Mean

Standard Deviation

Standard Deviation Score (SDS)

Title

Denominators

Categories

Title	Measurements
	BG000-2.5± 0.5 BG001

Weight

Weight was recorded from a single observation of the subject in light clothing or dressing gown with shoes removed.

The SDS was calculated as: SDS=[(value /M)^L - 1] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)

Mean

Standard Deviation

SDS

Title

Denominators

Categories

Title	Measurements
	BG000-2.0± 0.7 BG001

Body Mass Index (BMI)

BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2).

Mean

Standard Deviation

SDS

Title

Denominators

Categories

Title	Measurements
	BG000-0.3± 0.7 BG001

IGF-1

IGF-1 SDS was computed based on actual value of IGF-1, the mean reference value of IGF-1 and the SD reference value of IGF-1 as defined in the International Congress of Endocrinology, Lisbon, 2004

Mean

Standard Deviation

SDS

Title

Denominators

Categories

Title	Measurements
	BG000-1.8± 0.5 BG001

Mid-Parental target height

The mid-parental target height SDS is defined as: 0.4*(Mother's Height SDS+Father's Height SDS)

Mean

Standard Deviation

SDS

Title

Denominators

Categories

Title	Measurements
	BG000-0.5± 0.4 BG001

Bone age imputed

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0007.6± 1.7 BG0017.2± 1.8 BG002

Height Age

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0006.5± 1.6 BG0016.0± 1.5 BG002

Max stimulated GH

Mean

Standard Deviation

ng/mL

Title

Denominators

Categories

Title	Measurements
	BG00017.9± 8.9 BG00118.2± 8.4 BG002

IGFBP-3 SDS

Number of subjects analysed= 26,26,27,26 (Total 105)

IGFBP-3 SDS was computed based on actual value of IGFBP-3, the mean reference value of IGFBP-3 and the SD reference value of IGFBP-3 as defined in the International Congress of Endocrinology, Lisbon, 2004

Mean

Standard Deviation

SDS

Title

Denominators

Categories

Title	Measurements
	BG000-1.1± 0.7 BG001

Mother height

Number of subjects analysed= 24,23,25,25 (Total 97)

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000157± 5 BG001157± 5 BG002

Father height

Number of subjects analysed= 18,20,22,21 (Total = 81)

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000172± 4 BG001169± 5 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Height Velocity

Modified Intent-To-Treat (MITT): MITT population comprised all subjects who were randomized and had at least one post-baseline height measurement.

[n= 25,27,27,26]

Posted

Mean

Standard Deviation

cm/y

First year of treatment

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
OG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Units	Counts
Participants	OG00025 OG00127 OG00227 OG003

Title

Denominators

Categories

Title	Measurements
	OG0009.3± 1.7 OG00110.1± 1.3 OG0029.7± 2.5 OG003

Secondary

Height Velocity

Modified Intent-To-Treat (MITT): MITT population comprised all subjects who were randomized and had at least one post-baseline height measurement.

Posted

Mean

Standard Deviation

cm/y

Second, third and fourth year

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
OG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Secondary

Cumulative Change in Height Standard Deviation Score (SDS)

Modified Intent-To-Treat (MITT): MITT population comprised all subjects who were randomized and had at least one post-baseline height measurement.

Posted

Mean

Standard Deviation

SDS

First, second, third and fourth year

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002

Secondary

Predicted Adult Height (PAH)

Predicted Adult Height calculated by method, Roche-Wainer-Thissen (RWT) and mid-parental target height SDS.

Completers, the completer population consists of all subjects that remained in the study until a specific time point (ie; Year 1, Year 2, Year 3 and Year 4).

Posted

Mean

Standard Deviation

SDS

At baseline (Day 1), year 1,2,3 and 4

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections

Secondary

Total Change From Baseline (Day 1) in BMI SDS

BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2).

Completers, the completer population consists of all subjects that remained in the study until a specific time point (ie; Year 1, Year 2, Year 3 and Year 4).

Posted

Mean

Standard Deviation

SDS

At year 1,2,3,4 and end of study (visit 23) versus baseline (day 1)

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1

Secondary

Skeletal Maturation

Assessed by bone age. Bone age was determined by the radiograph.

Completers, the completer population consists of all subjects that remained in the study until a specific time point (ie; Year 1, Year 2, Year 3 and Year 4).

Posted

Mean

Standard Deviation

SDS

At baseline(day 1), year 1,2,3 and 4

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections

Secondary

Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH)

Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.

Posted

Mean

Standard Deviation

ng/mL

At Baseline (Day 1), Year 1,2,3 and 4

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
OG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Secondary

Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1)

Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.

Posted

Mean

Standard Deviation

ng/mL

At Baseline (Day 1), Year 1,2,3 and 4

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
OG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Secondary

Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1)

Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.

Posted

Mean

Standard Deviation

ng/mL

At Baseline (Day 1), Year 1,2,3 and 4

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
OG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Secondary

Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3)

Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.

Posted

Mean

Standard Deviation

ng/mL

At Baseline (Day 1), Year 1,2,3 and 4

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
OG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Secondary

Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS)

Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.

Posted

Mean

Standard Deviation

mg/L

At Baseline (Day 1), Year 1,2,3 and 4

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
OG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Secondary

Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP)

Modified Intent-to-Treat (MITT) Population comprised all subjects who were randomized and had at least one post-baseline height measurement.

Posted

Mean

Standard Deviation

pmol/L

At Baseline (Day 1), Year 1,2,3 and 4

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
OG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Secondary

Summary of Adverse Events With Number of Occurrences

A Data Monitoring Committee (DMC) was established to monitor subject safety

Safety population: Safety population consisted of all subjects who were randomized. Note that post baseline follow-up data were received for all subjects who were randomized.

Posted

Number

Number of events

Approximately up to 4 years.

ID	Title	Description
OG000	rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection
OG001	45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
OG002	45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections
OG003	45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Upper respiratory tract infection	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG00023 events10 affected26 at risk EG00119 events10 affected27 at risk EG00231 events9 affected27 at risk EG00337 events13 affected26 at risk
Otitis media	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0004 events4 affected26 at risk EG0017 events5 affected27 at risk EG0025 events3 affected27 at risk EG003
Viral infection	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG00010 events6 affected26 at risk EG0017 events3 affected27 at risk EG0026 events6 affected27 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0002 events1 affected26 at risk EG0013 events3 affected27 at risk EG0029 events5 affected27 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG00013 events5 affected26 at risk EG00117 events12 affected27 at risk EG0029 events7 affected27 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0008 events6 affected26 at risk EG0019 events3 affected27 at risk EG0024 events2 affected27 at risk EG003
Influenza	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0014 events3 affected27 at risk EG0026 events5 affected27 at risk EG003
Ear infection	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0005 events3 affected26 at risk EG0014 events2 affected27 at risk EG0026 events4 affected27 at risk EG003
Otitis externa	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0011 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Molluscum contagiosum	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Bronchitis	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0013 events1 affected27 at risk EG0024 events2 affected27 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0004 events3 affected26 at risk EG0015 events4 affected27 at risk EG00215 events4 affected27 at risk EG003
Pharyngitis	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0013 events2 affected27 at risk EG0020 events0 affected27 at risk EG003
Sinusitis	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG00025 events5 affected26 at risk EG00114 events7 affected27 at risk EG0025 events3 affected27 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0023 events1 affected27 at risk EG003
Varicella	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Tonsillitis	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0011 events1 affected27 at risk EG0023 events3 affected27 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0013 events3 affected27 at risk EG0020 events0 affected27 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA v11.0	Systematic Assessment	EG00017 events9 affected26 at risk EG0016 events5 affected27 at risk EG00212 events6 affected27 at risk EG003
Abdominal pain upper	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG00011 events7 affected26 at risk EG0018 events5 affected27 at risk EG0027 events3 affected27 at risk EG003
Diarrhea	Gastrointestinal disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0014 events3 affected27 at risk EG0022 events2 affected27 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA v11.0	Systematic Assessment	EG00010 events4 affected26 at risk EG0015 events4 affected27 at risk EG0027 events4 affected27 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0014 events4 affected27 at risk EG0026 events4 affected27 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0013 events3 affected27 at risk EG0020 events0 affected27 at risk EG003
Stomach discomfort	Gastrointestinal disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0012 events2 affected27 at risk EG0024 events3 affected27 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0012 events2 affected27 at risk EG0020 events0 affected27 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Pyrexia	General disorders	MedDRA v11.0	Systematic Assessment	EG00017 events9 affected26 at risk EG00127 events15 affected27 at risk EG00222 events4 affected27 at risk EG003
Injection site pain	General disorders	MedDRA v11.0	Systematic Assessment	EG0004 events4 affected26 at risk EG0012 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Malaise	General disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003
Injection site bruising	General disorders	MedDRA v11.0	Systematic Assessment	EG0004 events4 affected26 at risk EG0015 events4 affected27 at risk EG0024 events4 affected27 at risk EG003
Injection site hypertrophy	General disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0018 events6 affected27 at risk EG00213 events7 affected27 at risk EG003
Injection site induration	General disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0011 events1 affected27 at risk EG0022 events2 affected27 at risk EG003
Influenza like illness	General disorders	MedDRA v11.0	Systematic Assessment	EG0002 events1 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Injection site erythema	General disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0012 events2 affected27 at risk EG0020 events0 affected27 at risk EG003
Injection site urticaria	General disorders	MedDRA v11.0	Systematic Assessment	EG0003 events2 affected26 at risk EG0013 events3 affected27 at risk EG0022 events1 affected27 at risk EG003
Fatigue	General disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0013 events3 affected27 at risk EG0020 events0 affected27 at risk EG003
Feeling hot	General disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0012 events2 affected27 at risk EG0020 events0 affected27 at risk EG003
Headache	Nervous system disorders	MedDRA v11.0	Systematic Assessment	EG00040 events14 affected26 at risk EG00143 events14 affected27 at risk EG00239 events17 affected27 at risk EG003
Dizziness	Nervous system disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0014 events2 affected27 at risk EG0020 events0 affected27 at risk EG003
Migraine	Nervous system disorders	MedDRA v11.0	Systematic Assessment	EG0002 events1 affected26 at risk EG0013 events3 affected27 at risk EG0023 events3 affected27 at risk EG003
Tremor	Nervous system disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0012 events2 affected27 at risk EG0020 events0 affected27 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0012 events1 affected27 at risk EG0021 events1 affected27 at risk EG003
Skin hypertrophy	Skin and subcutaneous tissue disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0012 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0011 events1 affected27 at risk EG0026 events3 affected27 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Keratosis pilaris	Skin and subcutaneous tissue disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003
Hair texture abnormal	Skin and subcutaneous tissue disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0011 events1 affected27 at risk EG0022 events2 affected27 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Arthropod sting	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0003 events2 affected26 at risk EG0012 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0012 events2 affected27 at risk EG0020 events0 affected27 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Concussion	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Joint sprain	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0012 events2 affected27 at risk EG0024 events3 affected27 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0012 events2 affected27 at risk EG0020 events0 affected27 at risk EG003
Orthodontic appliance complication	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v11.0	Systematic Assessment	EG0007 events6 affected26 at risk EG00118 events14 affected27 at risk EG00216 events9 affected27 at risk EG003
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA v11.0	Systematic Assessment	EG0003 events3 affected26 at risk EG00111 events7 affected27 at risk EG00210 events7 affected27 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0012 events2 affected27 at risk EG0026 events3 affected27 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0011 events1 affected27 at risk EG0024 events3 affected27 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA v11.0	Systematic Assessment	EG0005 events2 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA v11.0	Systematic Assessment	EG0003 events3 affected26 at risk EG0012 events2 affected27 at risk EG0021 events1 affected27 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0011 events1 affected27 at risk EG0022 events2 affected27 at risk EG003
Tonsillar hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0012 events2 affected27 at risk EG0021 events1 affected27 at risk EG003
Adenoidal hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0011 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Hypoglycemia	Metabolism and nutrition disorders	MedDRA v11.0	Systematic Assessment	EG0003 events2 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v11.0	Systematic Assessment	EG0008 events7 affected26 at risk EG0017 events4 affected27 at risk EG0025 events5 affected27 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v11.0	Systematic Assessment	EG0007 events4 affected26 at risk EG00111 events8 affected27 at risk EG0028 events7 affected27 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v11.0	Systematic Assessment	EG0004 events3 affected26 at risk EG0015 events5 affected27 at risk EG0021 events1 affected27 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Scoliosis	Musculoskeletal and connective tissue disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0014 events3 affected27 at risk EG0022 events1 affected27 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA v11.0	Systematic Assessment	EG0002 events1 affected26 at risk EG0014 events2 affected27 at risk EG0021 events1 affected27 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0011 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0014 events3 affected27 at risk EG0023 events3 affected27 at risk EG003
Eye pain	Eye disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0011 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Myopia	Eye disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003
Vision blurred	Eye disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Conjunctivitis	Eye disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0014 events4 affected27 at risk EG0020 events0 affected27 at risk EG003
Insulin-like growth factor increased	Investigations	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Body temperature increased	Investigations	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0014 events3 affected27 at risk EG0023 events3 affected27 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0012 events2 affected27 at risk EG0020 events0 affected27 at risk EG003
Thyroxine free decreased	Investigations	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003
Weight decreased	Investigations	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0010 events0 affected27 at risk EG0023 events2 affected27 at risk EG003
Gynaecomastia	Reproductive system and breast disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003
Anxiety	Psychiatric disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Affective disorder	Psychiatric disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003
Attention	Psychiatric disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA v11.0	Systematic Assessment	EG0002 events2 affected26 at risk EG0012 events2 affected27 at risk EG0021 events1 affected27 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA v11.0	Systematic Assessment	EG0007 events4 affected26 at risk EG0011 events1 affected27 at risk EG0023 events3 affected27 at risk EG003
Tachycardia	Cardiac disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Enuresis	Renal and urinary disorders	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0011 events1 affected27 at risk EG0022 events2 affected27 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0022 events2 affected27 at risk EG003

ID	Term
C563867	Insulin-Like Growth Factor I Deficiency
D011628	Puberty, Delayed

ID	Term
D006058	Gonadal Disorders
D004700	Endocrine System Diseases

ID	Term
D019382	Human Growth Hormone
C000604197	mecasermin
D007267	Injections

ID	Term
D013006	Growth Hormone
D010908	Pituitary Hormones, Anterior
D010907	Pituitary Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D004333	Drug Administration Routes
D004358	Drug Therapy
D013812	Therapeutics

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	1. rhGH Alone	Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg once daily injection	1	26	26	26
EG001	2. 45 rhGH + 50 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections	1	27	27	27
EG002	3. 45 rhGH + 100 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections	2	27	27	27
EG003	4. 45 rhGH + 150 rhIGF-1	Increlex® (Mecasermin [rDNA origin] injection) + Nutropin AQ® (Somatropin [rDNA origin]): rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection	1	26	26	26

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Intracranial pressure increased	Nervous system disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG0030 events0 affected26 at risk
Forearm fracture	Injury, poisoning and procedural complications	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0021 events1 affected27 at risk EG003
Evans syndrome	Blood and lymphatic system disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0011 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0013 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Viral infection	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0011 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA v11.0	Systematic Assessment	EG0001 events1 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003
Hematuria	Renal and urinary disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0011 events1 affected27 at risk EG0020 events0 affected27 at risk EG003
Papilledema	Eye disorders	MedDRA v11.0	Systematic Assessment	EG0000 events0 affected26 at risk EG0010 events0 affected27 at risk EG0020 events0 affected27 at risk EG003