Individualized, Target-Driven Treatment Of Children With... | NCT00396097

Label	Type	Description	Intervention Names
Standard	Active Comparator	Standard daily HGH treatment	Drug: Genotropin
Formula-based	Active Comparator	Formula-based dose regimen	Drug: Genotropin

Name	Type	Description	Arm Group Labels	Other Names
Genotropin	Drug	Compare daily injections of formula-based HGH treatment to daily injections of standard HGH treatment in subjects with Idiopathic Short Stature over 24 months period followed by an exploratory 24 months period.

Measure	Description	Time Frame
Absolute On-target Difference (AOTD) at 24 Months	This was defined as an absolute difference between the 24-month height standard deviation score (SDS) and targeted 24-month height SDS (10th percentile (%), or -1.3 SDS). SDS indicates how similar the participant was to the reference population. These were calculated using 2000 Center for the Disease Control (CDC) growth reference tables (by age and gender).	2 years

Measure	Description	Time Frame
Variability of Height SDS at 24 Months	The continuous endpoint of variability of height SDS at 24 months was defined as the SD of the 24 month height SDS.	2 years
Time Cost (Months Until >= -2 SDS)

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Arkansas Children's Hospital		Little Rock	Alaska	72202	United States
Arkansas Children's Hospital

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Standard Dose Arm	The participants received subcutaneous genotropin, at a maintained standard dose of 0.37 mg/kg/week, throughout the four years.
FG001	Individualized Dose Arm

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

Absolute On-target Difference (AOTD) at 24 Months

This was defined as an absolute difference between the 24-month height standard deviation score (SDS) and targeted 24-month height SDS (10th percentile (%), or -1.3 SDS). SDS indicates how similar the participant was to the reference population. These were calculated using 2000 Center for the Disease Control (CDC) growth reference tables (by age and gender).

The Full Analysis Set (FAS) included all randomized subjects who received at least 1 dose of study treatment and had at least 1 post-baseline height SDS value available. Last observation carried forward (LOCF) rule was applied to impute Month 24 missing height SDS data.

Posted

Mean

Standard Deviation

Standard Deviation Score (SDS)

2 years

ID	Title	Description
OG000	Standard Dose Arm	The participants received subcutaneous genotropin daily, at maintained standard dose of 0.37 mg/kg/week, throughout the four years.
OG001	Individualized Dose Arm	The participants received subcutaneous genotropin daily, at formula-calculated dose (up to maximum dose of 0.7 mg/kg/week) for the initial 2 years and then lowered to one of two approximately physiological doses (0.18 mg/kg/week or 0.24 mg/kg/week) for the remaining 2 years.

Units	Counts
Participants	OG000114 OG001202

Title

Denominators

Categories

Title	Measurements
	OG0000.603± 0.2948 OG0010.625± 0.3003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis was that the individualized treatment arm was not superior to the standard treatment arm; alternative hypothesis that the individualized treatment arm was superior to the standard treatment arm with respect to the mean 24-month AOTD. Using a 2:1 randomization, a two sided sample t-test comparing the root AOTD between the 2 treatment arms with 80% power at a 5% level required 260 subjects. Assuming a 20% attrition rate, approximately 312 subjects were needed for this study.	ANCOVA		0.5762		Mean Difference (Final Values)	-0.006	Standard Error of the Mean	0.033	1-Sided	97.5	-0.071					No	Superiority or Other

Secondary

Variability of Height SDS at 24 Months

The continuous endpoint of variability of height SDS at 24 months was defined as the SD of the 24 month height SDS.

FAS included all randomized subjects who received at least 1 dose of study treatment and had at least 1 post-baseline height SDS value available. LOCF rule was applied to impute Month 24 missing height SDS data.

Posted

Mean

Standard Deviation

Standard Deviation Score (SDS)

2 years

ID	Title	Description
OG000	Standard Dose Arm	The participants received subcutaneous genotropin daily, at maintained standard dose of 0.37 mg/kg/week, throughout the four years.
OG001	Individualized Dose Arm	The participants received subcutaneous genotropin daily, at formula-calculated dose (up to maximum dose of 0.7 mg/kg/week) for the initial 2 years and then lowered to one of two approximately physiological doses (0.18 mg/kg/week or 0.24 mg/kg/week) for the remaining 2 years.

Units	Counts
Participants

Secondary

Time Cost (Months Until >= -2 SDS)

Time cost was defined as the number of months needed until height SDS was within the normal limit (ie, >= -2SDS).

Full analysis set (FAS) included all randomized subjects who received at least 1 dose of study treatment and had at least 1 post-baseline height SDS value available.

Posted

Median

95% Confidence Interval

Months

2 years

ID	Title	Description
OG000	Standard Dose Arm	The participants received subcutaneous genotropin daily, at maintained standard dose of 0.37 mg/kg/week, throughout the four years.
OG001	Individualized Dose Arm	The participants received subcutaneous genotropin daily, at formula-calculated dose (up to maximum dose of 0.7 mg/kg/week) for the initial 2 years and then lowered to one of two approximately physiological doses (0.18 mg/kg/week or 0.24 mg/kg/week) for the remaining 2 years.

Units	Counts
Participants	OG000

Secondary

Computed Cost of Height Gain at 48 Months

The computed cost of height gain was defined as the amount of drug used relative to the observed height-gain, in terms of mg/cm, this was calculated at Month 48.

Posted

Mean

Standard Deviation

mg/cm

4 years

ID	Title	Description
OG000	Standard Dose Arm	The participants received subcutaneous genotropin daily, at maintained standard dose of 0.37 mg/kg/week, throughout the four years.
OG001	Individualized Dose Arm Overall	The participants received subcutaneous genotropin daily, at formula-calculated dose (up to maximum dose of 0.7 mg/kg/week) for the initial 2 years and then lowered to one of two approximately physiological doses (0.18 mg/kg/week or 0.24 mg/kg/week) for the remaining 2 years. The combined individualized dose group (N=202) includes 179 subjects who, at the start of the maintenance phase, were randomized to either 0.18 or 0.24 mg/kg/week dose subgroup. The remaining 23 subjects were not randomized at the start of the maintenance phase either due to early termination (n=19), or because they were initially randomized to the individualized dose, had the dose calculated to 0 mg, and had received the standard dose for the remainder of the study (n=4).

Secondary

Estimated Cost of Height Gain Estimated Until Full Adult Height (FAH) at 48 Months

The estimated cost of long-term height gain until FAH was calculated.

Full analysis set (FAS) included all randomized subjects who received at least 1 dose of study treatment and had at least 1 post-baseline height SDS value available. LOCF rule was applied to impute Month 24 missing height SDS data.

Posted

Mean

Standard Deviation

mg/cm

4 years

ID	Title	Description
OG000	Standard Dose Arm	The participants received subcutaneous genotropin daily, at maintained standard dose of 0.37 mg/kg/week, throughout the four years.
OG001	Individualized Dose Arm Overall	The participants received subcutaneous genotropin daily, at formula-calculated dose (up to maximum dose of 0.7 mg/kg/week) for the initial 2 years and then lowered to one of two approximately physiological doses (0.18 mg/kg/week or 0.24 mg/kg/week) for the remaining 2 years. The combined individualized dose group (N=202) includes 179 subjects who, at the start of the maintenance phase, were randomized to either 0.18 or 0.24 mg/kg/week dose subgroup. The remaining 23 subjects were not randomized at the start of the maintenance phase either due to early termination (n=19), or because they were initially randomized to the individualized dose, had the dose calculated to 0 mg, and had received the standard dose for the remainder of the study (n=4).

Secondary

Change From Baseline in Height SDS at 48 Months.

Change in height SDS was measured at 48 months.

Posted

Mean

Standard Deviation

Standard Deviation Score (SDS)

4 years

ID	Title	Description
OG000	Standard Dose Arm	The participants received subcutaneous genotropin daily, at maintained standard dose of 0.37 mg/kg/week, throughout the four years.
OG001	Individualized Dose Arm Overall	The participants received subcutaneous genotropin daily, at formula-calculated dose (up to maximum dose of 0.7 mg/kg/week) for the initial 2 years and then lowered to one of two approximately physiological doses (0.18 mg/kg/week or 0.24 mg/kg/week) for the remaining 2 years. The combined individualized dose group (N=202) includes 179 subjects who, at the start of the maintenance phase, were randomized to either 0.18 or 0.24 mg/kg/week dose subgroup. The remaining 23 subjects were not randomized at the start of the maintenance phase either due to early termination (n=19), or because they were initially randomized to the individualized dose, had the dose calculated to 0 mg, and had received the standard dose for the remainder of the study (n=4).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arnold-chiari malformation	Congenital, familial and genetic disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Device breakage	General disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected198 at risk
Appendicitis	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0011 events1 affected198 at risk
Pneumonia	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0002 events2 affected118 at risk EG0010 events0 affected198 at risk
Postoperative wound infection	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Accident	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Facial bones fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Foreign Body	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected198 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected198 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected198 at risk
Scoliosis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Convulsion	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0011 events1 affected198 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Pneumocephalus	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Abnormal behaviour	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0000 events0 affected118 at risk EG0011 events1 affected198 at risk
Affective disorder	Psychiatric disorders	MedDRA 15.0	Non-systematic Assessment	EG0001 events1 affected118 at risk EG0010 events0 affected198 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0002 events2 affected118 at risk EG0010 events0 affected198 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0008 affected118 at risk EG00126 affected198 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Non-systematic Assessment	EG00010 affected118 at risk EG00117 affected198 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0006 affected118 at risk EG00119 affected198 at risk
Hypersensitivity	Immune system disorders	MedDRA 15.0	Non-systematic Assessment	EG0006 affected118 at risk EG0016 affected198 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 15.0	Non-systematic Assessment	EG0005 affected118 at risk EG00113 affected198 at risk
Headache	Nervous system disorders	MedDRA 15.0	Non-systematic Assessment	EG00033 affected118 at risk EG00159 affected198 at risk
Pyrexia	General disorders	MedDRA 15.0	Non-systematic Assessment	EG00013 affected118 at risk EG00122 affected198 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0002 affected118 at risk EG00110 affected198 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0006 affected118 at risk EG0016 affected198 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0009 affected118 at risk EG00117 affected198 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0007 affected118 at risk EG00112 affected198 at risk
Nausea	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG0005 affected118 at risk EG00111 affected198 at risk
Vomiting	Gastrointestinal disorders	MedDRA 15.0	Non-systematic Assessment	EG00015 affected118 at risk EG00121 affected198 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG00015 affected118 at risk EG00124 affected198 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG00014 affected118 at risk EG00117 affected198 at risk
Scoliosis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Non-systematic Assessment	EG00011 affected118 at risk EG00119 affected198 at risk
Ear infection	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0001 affected118 at risk EG00111 affected198 at risk
Gastroenteritis	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG00010 affected118 at risk EG00111 affected198 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0007 affected118 at risk EG00115 affected198 at risk
Influenza	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG00016 affected118 at risk EG00122 affected198 at risk
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0008 affected118 at risk EG00125 affected198 at risk
Otitis externa	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0002 affected118 at risk EG00110 affected198 at risk
Otitis media	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG00011 affected118 at risk EG00123 affected198 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG00015 affected118 at risk EG00130 affected198 at risk
Sinusitis	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0009 affected118 at risk EG00123 affected198 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG00028 affected118 at risk EG00145 affected198 at risk
Viral infection	Infections and infestations	MedDRA 15.0	Non-systematic Assessment	EG0009 affected118 at risk EG00111 affected198 at risk

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

ID	Title	Description
BG000	Standard Dose Arm	The participants received subcutaneous genotropin daily, at a maintained standard dose of 0.37 mg/kg/week, throughout the four years.
BG001	Individualized Dose Arm	The participants received subcutaneous genotropin daily, at formula-calculated dose (up to maximum dose of 0.7 mg/kg/week) for the initial 2 years and then lowered to one of two approximately physiological doses (0.18 mg/kg/week or 0.24 mg/kg/week) for the remaining 2 years.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Standard Dose Arm	The participants received subcutaneous genotropin daily, at a maintained standard dose of 0.37 mg/kg/week, throughout the four years.			13	118	103	118
EG001	Individualized Dose Arm	The participants received subcutaneous genotropin daily, at formula-calculated dose (up to maximum dose of 0.7 mg/kg/week) for the initial 2 years and then lowered to one of two approximately physiological doses (0.18 mg/kg/week or 0.24 mg/kg/week) for the remaining 2 years.			7	198	165	198