Long-Term Growth and Skeletal Effects of Early Growth Hormone Treatment in Turner Syndrome

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00266656
• Collaborator: (none)
• Enrollment: 69
• Locations: 9
• Arms: 2
• Duration (Months): 117
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an extension study that will gather long-term data on the effect of early growth hormone (GH) treatment on adult height and other aspects of health and development in girls with Turner syndrome. The main purpose is to determine whether girls who received 2 years of GH treatment before 6 years of age achieve taller adult height than girls who were untreated during this time. The study will also look at middle ear and hearing function, and cognitive and behavioral development. Protocol completion is defined as attainment of height velocity less than or equal to 1.0 cm/year, or bone age greater than or equal to 15 years.

Condition or Disease	Intervention/Treatment	Phase
Turner Syndrome	Drug: Humatrope	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Early Growth Hormone Treatment on Long-term Growth and Skeletal Maturation in Girls With Turner Syndrome
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental 1 Control No drug administration in B9R-US-GDFG (NCT00406926). Humatrope according to investigator's clinical practice and guided by the approved package insert on whether treatment is given.	Drug: Humatrope; According to investigator's clinical practice and guided by the approved package insert; Other Names: LY137998 Somatropin Growth hormone
Experimental: Experimental 2 Humatrope Humatrope according to investigator's clinical practice and guided by the approved package insert on whether treatment is given.	Drug: Humatrope; According to investigator's clinical practice and guided by the approved package insert; Other Names: LY137998 Somatropin Growth hormone

Outcome Measures

Primary Outcome Measures

1. Most Mature Height Standard Deviation Score (SDS) [Baseline through End of Study (10 years)]

   SDS reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height.

Secondary Outcome Measures

1. Height SDS at Various Ages [Age 10, Age 13, Age 16]

   SDS reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height.

2. Age at Attainment of Tanner 2 Breast Development [Baseline through End of Study (10 years)]

   The Tanner 2 breast development is the age at first evidence of breast development.

3. Chronological Age at First Visit Participant Attained Bone Age of 14.5 Years [Baseline through End of Study (10 years)]

   Bone age was measured by standard radiograph, x-ray at baseline and annually for 10 years or until attainment of height velocity less than or equal to 1.0 centimeter per year (cm/year) and bone age greater or equal to 15 years.

4. Reports of Serious Adverse Events [Baseline through End of Study (10 years)]

   Number of serious adverse events (SAEs) reported. Any adverse event from this study that results in one of the following outcomes, or is significant for any other reason were reported as an SAE: death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a study subject, significant for any other reason (includes cancer, other than superficial, and basal cell or squamous cell carcinomas of the skin, that did not meet other serious adverse event criteria). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

5. Percentage of Participants With Occurrence of Pre-specified Clinically Relevant Events [Baseline through End of Study (10 years)]

   Percentage of participants for whom certain non-serious, pre-specified adverse events (AEs; those that are commonly observed in Turner syndrome or are known to be related to GH treatment: impaired glucose tolerance, diabetes mellitus, hypothyroidism, benign intracranial hypertension, scoliosis, slipped capital femoral epiphysis, solid tumor/leukemia, pancreatitis, ear infections, and high blood pressure) are reported.

6. Percentage of Participants With Abnormal Tympanometry Results [Baseline, Age 10, Age 16, End of Study (10 years)]

   Percentage of participants with abnormal tympanometry [defined as middle ear dysfunction / middle ear effusion / patent pressure equalizer tube or possible tympanic membrane perforation] results at baseline, age 10 years, and age 16 years or endpoint.

7. Percentage of Participants With Prevalence of Abnormal Audiometry Results [Baseline, Age 10, Age 16, End of Study (10 years)]

   Percentage of participants with abnormal Audiometry results at baseline, age 10 years, and age 16 years or endpoint. Prevalence was calculated as number of participants with abnormal hearing divided by number of participants with measurable pure tone audiometry results at that visit.

8. Percentage of Participants With Abnormal Audiometry Results Based on Pure Tone Average (PTA) [Baseline, Age 10, Age 16, End of Study (10 years)]

   Percentage of participants with abnormal Audiometry results at baseline, age 10 years, and age 16 years or endpoint. PTA is defined as the average of pure tone hearing thresholds at 500, 1000 and 2000 Hz (Hertz), calculated separately for each ear and for each testing method (air or bone); normal PTA is defined as pure tone hearing threshold less than or equal to 20 dB HL (decibels Hearing Level), and abnormal PTA is defined as pure tone hearing threshold greater than 20 DB HL.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 20 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Previously randomized in study B9R-US-GDFG (NCT00406926)

• Karyotype-proven Turner syndrome

Exclusion Criteria:

• Immediate family members of study site personnel directly affiliated with the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital of Los Angeles	Los Angeles	California	United States	90027
2	Children's Hospital	Aurora	Colorado	United States	80045
3	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
4	Children's Hospital of Chicago Research Center	Chicago	Illinois	United States	60611
5	Riley Hosptial for Children	Indianapolis	Indiana	United States	46202
6	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
7	University of NC at Chapel Hill School of Medicine	Chapel Hill	North Carolina	United States	27514
8	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
9	Childrens Hospital and Medical Center	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hrs), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00266656
• Other Study ID Numbers: 10088; B9R-US-GDGH
• First Posted: Dec 19, 2005
• Last Update Posted: Mar 31, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Turner Syndrome; Gonadal Dysgenesis; Syndrome; Hormones

Study Results

Participant Flow

Recruitment Details	To be included in this study, participants had to be females with karyotype-proven Turner syndrome who were previously randomized in Study B9R-US-GDFG (NCT00406926).

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Period Title: Overall Study
STARTED	36	33
COMPLETED	22	20
NOT COMPLETED	14	13

Baseline Characteristics

Arm/Group Title	Early Treated	Early Untreated	Total
Arm/Group Description	Early treated n=36	Early untreated n=33	Total of all reporting groups
Overall Participants	36	33	69
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.29 (1.22)	8.41 (1.30)	8.35 (1.25)
Sex: Female, Male (Count of Participants)
Female	36 100%	33 100%	69 100%
Male	0 0%	0 0%	0 0%
Height (centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter]	124.34 (10.08)	121.06 (9.76)	122.77 (9.99)
Height Standard Deviation Score (SDS) (Standard Deviation Score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Standard Deviation Score]	-0.84 (1.22)	-1.48 (1.23)	-1.15 (1.26)
Bone Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.73 (1.55)	8.34 (1.57)	8.54 (1.56)

Outcome Measures

1. Primary Outcome

Title	Most Mature Height Standard Deviation Score (SDS)
Description	SDS reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height.
Time Frame	Baseline through End of Study (10 years)

Outcome Measure Data

Analysis Population Description

All participants who achieved Near Adult Height (NAH). NAH is defined as first height measured when height velocity is less than or equal to 2.0 centimeter per year over the preceding year (in the absence of growth-impairing process such as hypothyroidism or inflammatory bowel disease), or bone age greater than or equal to14.5 years.

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Measure Participants	25	26
Mean (Standard Deviation) [standard deviation score]	-1.37 (1.09)	-1.60 (1.21)

2. Secondary Outcome

Title	Height SDS at Various Ages
Description	SDS reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height.
Time Frame	Age 10, Age 13, Age 16

Outcome Measure Data

Analysis Population Description

All participants who had a baseline visit and at least one post-baseline visit.

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Measure Participants	35	32
Age 10 (n=32, 30)	-0.66 (1.16)	-1.28 (1.17)
Age 13 (n=29, 29)	-1.29 (1.24)	-1.87 (1.16)
Age 16 (n=18, 18)	-1.66 (1.11)	-1.69 (1.30)

3. Secondary Outcome

Title	Age at Attainment of Tanner 2 Breast Development
Description	The Tanner 2 breast development is the age at first evidence of breast development.
Time Frame	Baseline through End of Study (10 years)

Outcome Measure Data

Analysis Population Description

All participants who had a baseline visit and at least one post-baseline visit.

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Measure Participants	35	32
Mean (Standard Error) [years]	11.80 (0.26)	12.14 (0.31)

4. Secondary Outcome

Title	Chronological Age at First Visit Participant Attained Bone Age of 14.5 Years
Description	Bone age was measured by standard radiograph, x-ray at baseline and annually for 10 years or until attainment of height velocity less than or equal to 1.0 centimeter per year (cm/year) and bone age greater or equal to 15 years.
Time Frame	Baseline through End of Study (10 years)

Outcome Measure Data

Analysis Population Description

All participants who achieved Near Adult Height (NAH). NAH is defined as first height measured when height velocity is less than or equal to 2.0 centimeter per year over the preceding year (in the absence of growth-impairing process such as hypothyroidism or inflammatory bowel disease), or bone age greater than or equal to14.5 years.

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Measure Participants	25	26
Mean (Standard Error) [years]	14.64 (0.25)	15.26 (0.23)

5. Secondary Outcome

Title	Reports of Serious Adverse Events
Description	Number of serious adverse events (SAEs) reported. Any adverse event from this study that results in one of the following outcomes, or is significant for any other reason were reported as an SAE: death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a study subject, significant for any other reason (includes cancer, other than superficial, and basal cell or squamous cell carcinomas of the skin, that did not meet other serious adverse event criteria). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time Frame	Baseline through End of Study (10 years)

Outcome Measure Data

Analysis Population Description

All participants who had a baseline visit, regardless of whether or not they received Humatrope at any time.

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Measure Participants	36	33
Number [events]	8	5

6. Secondary Outcome

Title	Percentage of Participants With Occurrence of Pre-specified Clinically Relevant Events
Description	Percentage of participants for whom certain non-serious, pre-specified adverse events (AEs; those that are commonly observed in Turner syndrome or are known to be related to GH treatment: impaired glucose tolerance, diabetes mellitus, hypothyroidism, benign intracranial hypertension, scoliosis, slipped capital femoral epiphysis, solid tumor/leukemia, pancreatitis, ear infections, and high blood pressure) are reported.
Time Frame	Baseline through End of Study (10 years)

Outcome Measure Data

Analysis Population Description

All participants who had a baseline visit, regardless of whether or not they received Humatrope at any time.

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Measure Participants	36	33
Baseline Ear infections	13.9 38.6%	18.2 55.2%
Baseline High Blood Pressure	0 0%	3.0 9.1%
Baseline Hypothyroidism	13.9 38.6%	6.1 18.5%
Baseline Scoliosis	22.2 61.7%	9.1 27.6%
Year 1 Ear infections	38.9 108.1%	39.4 119.4%
Year 1 High Blood Pressure	0 0%	3.0 9.1%
Year 1 Hypothyroidism	11.1 30.8%	12.1 36.7%
Year 1 Scoliosis	16.7 46.4%	21.2 64.2%
Year 2 Diabetes	2.8 7.8%	0 0%
Year 2 Dilatation of the Aorta	0 0%	3.0 9.1%
Year 2 Ear infections	33.3 92.5%	27.3 82.7%
Year 2 High Blood Pressure	0 0%	3.0 9.1%
Year 2 Hypothyroidism	11.1 30.8%	12.1 36.7%
Year 2 Scoliosis	22.2 61.7%	24.2 73.3%
Year 3 Diabetes	2.8 7.8%	0 0%
Year 3 Dilatation of the Aorta	0 0%	6.1 18.5%
Year 3 Ear infections	30.6 85%	36.4 110.3%
Year 3 High Blood Pressure	0 0%	3.0 9.1%
Year 3 Hypothyroidism	11.1 30.8%	12.1 36.7%
Year 3 Scoliosis	25.0 69.4%	27.3 82.7%
Year 4 Diabetes	2.8 7.8%	0 0%
Year 4 Dilatation of the Aorta	0 0%	6.1 18.5%
Year 4 Ear infections	16.7 46.4%	30.3 91.8%
Year 4 High Blood Pressure	0 0%	3.0 9.1%
Year 4 Hypothyroidism	11.1 30.8%	12.1 36.7%
Year 4 Scoliosis	25.0 69.4%	27.3 82.7%
Year 5 Diabetes	2.8 7.8%	0 0%
Year 5 Dilatation of the Aorta	0 0%	6.1 18.5%
Year 5 Ear infections	22.2 61.7%	27.3 82.7%
Year 5 High Blood Pressure	0 0%	3.0 9.1%
Year 5 Hypothyroidism	13.9 38.6%	18.2 55.2%
Year 5 Scoliosis	25.0 69.4%	27.3 82.7%
Year 6 Diabetes	2.8 7.8%	0 0%
Year 6 Dilatation of the Aorta	0 0%	9.1 27.6%
Year 6 Ear infections	19.4 53.9%	24.2 73.3%
Year 6 High Blood Pressure	0 0%	3.0 9.1%
Year 6 Hypothyroidism	13.9 38.6%	18.2 55.2%
Year 6 Scoliosis	16.7 46.4%	30.3 91.8%
Year 7 Diabetes	2.8 7.8%	0 0%
Year 7 Dilatation of the Aorta	0 0%	9.1 27.6%
Year 7 Ear infections	19.4 53.9%	18.2 55.2%
Year 7 High Blood Pressure	0 0%	3.0 9.1%
Year 7 Hypothyroidism	13.9 38.6%	15.2 46.1%
Year 7 Scoliosis	13.9 38.6%	30.3 91.8%
Year 8 Diabetes	2.8 7.8%	0 0%
Year 8 Dilatation of the Aorta	2.8 7.8%	9.1 27.6%
Year 8 Ear infections	13.9 38.6%	18.2 55.2%
Year 8 High Blood Pressure	0 0%	3.0 9.1%
Year 8 Hypothyroidism	5.6 15.6%	12.1 36.7%
Year 8 Scoliosis	13.9 38.6%	33.3 100.9%
Year 9 Dilatation of the Aorta	0 0%	3.0 9.1%
Year 9 Ear infections	2.8 7.8%	3.0 9.1%
Year 9 High Blood Pressure	0 0%	3.0 9.1%
Year 9 Hypothyroidism	2.8 7.8%	6.1 18.5%
Year 9 Scoliosis	5.6 15.6%	9.1 27.6%
Year 10 Scoliosis	2.8 7.8%	0 0%

7. Secondary Outcome

Title	Percentage of Participants With Abnormal Tympanometry Results
Description	Percentage of participants with abnormal tympanometry [defined as middle ear dysfunction / middle ear effusion / patent pressure equalizer tube or possible tympanic membrane perforation] results at baseline, age 10 years, and age 16 years or endpoint.
Time Frame	Baseline, Age 10, Age 16, End of Study (10 years)

Outcome Measure Data

Analysis Population Description

All participants who had a baseline visit, regardless of whether or not they received Humatrope at any time.

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Measure Participants	36	33
Baseline Right Ear	44.4 123.3%	54.5 165.2%
Baseline Left Ear	47.2 131.1%	45.5 137.9%
Age 10 Right Ear	27.8 77.2%	15.2 46.1%
Age 10 Left Ear	27.8 77.2%	15.2 46.1%
Age 16 Right Ear	2.8 7.8%	9.1 27.6%
Age 16 Left Ear	2.8 7.8%	3.0 9.1%
Endpoint Right Ear	8.3 23.1%	12.1 36.7%
Endpoint Left Ear	11.1 30.8%	9.1 27.6%

8. Secondary Outcome

Title	Percentage of Participants With Prevalence of Abnormal Audiometry Results
Description	Percentage of participants with abnormal Audiometry results at baseline, age 10 years, and age 16 years or endpoint. Prevalence was calculated as number of participants with abnormal hearing divided by number of participants with measurable pure tone audiometry results at that visit.
Time Frame	Baseline, Age 10, Age 16, End of Study (10 years)

Outcome Measure Data

Analysis Population Description

All participants who had a baseline visit, regardless of whether or not they received Humatrope at any time.

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Measure Participants	36	33
Baseline Visit (n=36, 33)	52.8 146.7%	48.5 147%
Age 10 (n=27, 24)	44.4 123.3%	29.2 88.5%
Age 16 (n=7, 9)	85.7 238.1%	66.7 202.1%
Endpoint (n=24, 22)	37.5 104.2%	40.9 123.9%

9. Secondary Outcome

Title	Percentage of Participants With Abnormal Audiometry Results Based on Pure Tone Average (PTA)
Description	Percentage of participants with abnormal Audiometry results at baseline, age 10 years, and age 16 years or endpoint. PTA is defined as the average of pure tone hearing thresholds at 500, 1000 and 2000 Hz (Hertz), calculated separately for each ear and for each testing method (air or bone); normal PTA is defined as pure tone hearing threshold less than or equal to 20 dB HL (decibels Hearing Level), and abnormal PTA is defined as pure tone hearing threshold greater than 20 DB HL.
Time Frame	Baseline, Age 10, Age 16, End of Study (10 years)

Outcome Measure Data

Analysis Population Description

All participants who had a baseline visit, regardless of whether or not they received Humatrope at any time.

Arm/Group Title	Early Treated	Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
Measure Participants	36	33
Baseline Left Ear Air (n=36, 32)	30.6 85%	31.3 94.8%
Baseline Left Ear Bone (n=36, 32)	2.8 7.8%	0.0 0%
Baseline Right Ear Air (n=36, 32)	22.2 61.7%	37.5 113.6%
Baseline Right Ear Bone (n=36, 32)	22.2 61.7%	2.8 8.5%
Age 10 Left Ear Air (n=27, 21)	29.6 82.2%	14.3 43.3%
Age 10 Left Ear Bone (n=27, 21)	0.0 0%	0.0 0%
Age 10 Right Ear Air (n=27, 22)	14.8 41.1%	18.2 55.2%
Age 10 Right Ear Bone (n=27, 22)	0.0 0%	9.1 27.6%
Age 16 Left Ear Air (n=7, 9)	57.1 158.6%	66.7 202.1%
Age 16 Left Ear Bone (n=7, 9)	0.0 0%	0.0 0%
Age 16 Right Ear Air (n=7, 9)	28.6 79.4%	33.3 100.9%
Age 16 Right Ear Bone (n=7, 9)	0.0 0%	22.2 67.3%
Endpoint Left Ear Air (n=20, 20)	30.0 83.3%	35.0 106.1%
Endpoint Left Ear Bone (n=20, 20)	5.0 13.9%	20.0 60.6%
Endpoint Right Ear Air (n=20, 20)	20.0 55.6%	35.0 106.1%
Endpoint Right Ear Bone (n=20, 20)	10.0 27.8%	25.0 75.8%

Adverse Events

Adverse Event Reporting Description	All enrolled/started participants.
Arm/Group Title	Early Treated		Early Untreated
Arm/Group Description	Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Humatrope administered in B9R-US-GDFG (NCT00406926).		Humatrope administered according to investigator's clinical practice and guided by the approved package insert. Control: Humatrope was not administered in B9R-US-GDFG (NCT00406926).
All Cause Mortality
	Early Treated		Early Untreated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Early Treated		Early Untreated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/36 (16.7%)		5/33 (15.2%)
Congenital, familial and genetic disorders
Anomalous pulmonary venous connection	0/36 (0%)	0	1/33 (3%)	1
Atrial septal defect	1/36 (2.8%)	1	0/33 (0%)	0
Pterygium colli	0/36 (0%)	0	1/33 (3%)	1
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/36 (2.8%)	1	0/33 (0%)	0
Infections and infestations
Cellulitis	0/36 (0%)	0	1/33 (3%)	1
Gastroenteritis	1/36 (2.8%)	1	0/33 (0%)	0
Lobar pneumonia	0/36 (0%)	0	1/33 (3%)	1
Pneumonia	0/36 (0%)	0	1/33 (3%)	1
Musculoskeletal and connective tissue disorders
Scoliosis	2/36 (5.6%)	2	0/33 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Medulloblastoma	1/36 (2.8%)	1	0/33 (0%)	0
Nervous system disorders
Headache	1/36 (2.8%)	1	0/33 (0%)	0
Respiratory, thoracic and mediastinal disorders
Mediastinal mass	1/36 (2.8%)	1	0/33 (0%)	0
Other (Not Including Serious) Adverse Events
	Early Treated		Early Untreated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/36 (94.4%)		32/33 (97%)
Cardiac disorders
Palpitations	2/36 (5.6%)	2	0/33 (0%)	0
Ear and labyrinth disorders
Conductive deafness	4/36 (11.1%)	4	1/33 (3%)	1
Ear pain	6/36 (16.7%)	8	3/33 (9.1%)	4
Hearing impaired	2/36 (5.6%)	2	3/33 (9.1%)	3
Tympanic membrane perforation	7/36 (19.4%)	8	2/33 (6.1%)	2
Endocrine disorders
Autoimmune thyroiditis	0/36 (0%)	0	2/33 (6.1%)	2
Goitre	2/36 (5.6%)	2	0/33 (0%)	0
Hypothyroidism	4/36 (11.1%)	4	5/33 (15.2%)	5
Eye disorders
Myopia	2/36 (5.6%)	2	1/33 (3%)	1
Gastrointestinal disorders
Abdominal pain	4/36 (11.1%)	4	2/33 (6.1%)	2
Abdominal pain upper	1/36 (2.8%)	1	3/33 (9.1%)	3
Coeliac disease	1/36 (2.8%)	1	3/33 (9.1%)	3
Constipation	3/36 (8.3%)	3	2/33 (6.1%)	2
Diarrhoea	5/36 (13.9%)	5	5/33 (15.2%)	5
Gastrooesophageal reflux disease	2/36 (5.6%)	2	2/33 (6.1%)	2
Tooth malformation	2/36 (5.6%)	2	1/33 (3%)	1
Toothache	2/36 (5.6%)	2	0/33 (0%)	0
Vomiting	12/36 (33.3%)	12	3/33 (9.1%)	3
General disorders
Pain	2/36 (5.6%)	2	0/33 (0%)	0
Peripheral swelling	2/36 (5.6%)	2	0/33 (0%)	0
Pyrexia	11/36 (30.6%)	11	8/33 (24.2%)	8
Immune system disorders
Drug hypersensitivity	2/36 (5.6%)	2	0/33 (0%)	0
Multiple allergies	2/36 (5.6%)	2	0/33 (0%)	0
Seasonal allergy	5/36 (13.9%)	5	2/33 (6.1%)	2
Infections and infestations
Bronchitis	5/36 (13.9%)	5	4/33 (12.1%)	4
Conjunctivitis	4/36 (11.1%)	4	3/33 (9.1%)	3
Croup infectious	2/36 (5.6%)	2	0/33 (0%)	0
Ear infection	7/36 (19.4%)	7	2/33 (6.1%)	2
Eye infection	2/36 (5.6%)	2	0/33 (0%)	0
Gastroenteritis viral	7/36 (19.4%)	7	4/33 (12.1%)	5
Impetigo	2/36 (5.6%)	2	1/33 (3%)	1
Influenza	6/36 (16.7%)	6	3/33 (9.1%)	3
Kidney infection	2/36 (5.6%)	2	0/33 (0%)	0
Mononucleosis syndrome	0/36 (0%)	0	2/33 (6.1%)	2
Nasopharyngitis	8/36 (22.2%)	9	4/33 (12.1%)	5
Otitis externa	3/36 (8.3%)	4	5/33 (15.2%)	6
Otitis media	9/36 (25%)	11	12/33 (36.4%)	14
Pharyngitis streptococcal	4/36 (11.1%)	4	9/33 (27.3%)	9
Pneumonia	2/36 (5.6%)	2	2/33 (6.1%)	2
Sinusitis	7/36 (19.4%)	7	7/33 (21.2%)	7
Upper respiratory tract infection	1/36 (2.8%)	1	6/33 (18.2%)	7
Urinary tract infection	8/36 (22.2%)	9	0/33 (0%)	0
Vaginal infection	2/36 (5.6%)	2	0/33 (0%)	0
Viral infection	4/36 (11.1%)	5	0/33 (0%)	0
Injury, poisoning and procedural complications
Joint dislocation	2/36 (5.6%)	2	2/33 (6.1%)	2
Ligament sprain	0/36 (0%)	0	2/33 (6.1%)	2
Radius fracture	3/36 (8.3%)	3	2/33 (6.1%)	2
Wrist fracture	0/36 (0%)	0	2/33 (6.1%)	2
Investigations
Echocardiogram normal	2/36 (5.6%)	2	6/33 (18.2%)	6
Electrocardiogram normal	1/36 (2.8%)	1	2/33 (6.1%)	2
Ultrasound kidney normal	2/36 (5.6%)	2	2/33 (6.1%)	2
Ultrasound scan normal	0/36 (0%)	0	2/33 (6.1%)	2
Metabolism and nutrition disorders
Hyperlipidaemia	3/36 (8.3%)	3	1/33 (3%)	1
Musculoskeletal and connective tissue disorders
Kyphosis	5/36 (13.9%)	5	3/33 (9.1%)	3
Neck pain	2/36 (5.6%)	2	0/33 (0%)	0
Scoliosis	7/36 (19.4%)	7	10/33 (30.3%)	10
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma	2/36 (5.6%)	2	0/33 (0%)	0
Melanocytic naevus	11/36 (30.6%)	11	9/33 (27.3%)	9
Skin papilloma	6/36 (16.7%)	7	4/33 (12.1%)	4
Nervous system disorders
Headache	11/36 (30.6%)	13	9/33 (27.3%)	10
Psychiatric disorders
Anxiety	7/36 (19.4%)	7	6/33 (18.2%)	6
Depression	2/36 (5.6%)	2	3/33 (9.1%)	3
Insomnia	2/36 (5.6%)	2	1/33 (3%)	1
Obsessive-compulsive disorder	2/36 (5.6%)	2	2/33 (6.1%)	2
Renal and urinary disorders
Dysuria	2/36 (5.6%)	2	0/33 (0%)	0
Enuresis	1/36 (2.8%)	1	2/33 (6.1%)	2
Reproductive system and breast disorders
Dysmenorrhoea	3/36 (8.3%)	3	2/33 (6.1%)	2
Respiratory, thoracic and mediastinal disorders
Cough	8/36 (22.2%)	8	6/33 (18.2%)	6
Nasal congestion	1/36 (2.8%)	1	3/33 (9.1%)	3
Oropharyngeal pain	5/36 (13.9%)	5	4/33 (12.1%)	4
Respiratory disorder	1/36 (2.8%)	1	2/33 (6.1%)	2
Rhinorrhoea	2/36 (5.6%)	2	3/33 (9.1%)	3
Sinus congestion	2/36 (5.6%)	2	1/33 (3%)	1
Skin and subcutaneous tissue disorders
Acne	3/36 (8.3%)	3	0/33 (0%)	0
Eczema	2/36 (5.6%)	2	1/33 (3%)	1
Keloid scar	2/36 (5.6%)	2	1/33 (3%)	1
Rash	0/36 (0%)	0	5/33 (15.2%)	5
Seborrhoea	1/36 (2.8%)	1	3/33 (9.1%)	3
Seborrhoeic dermatitis	1/36 (2.8%)	1	3/33 (9.1%)	3
Social circumstances
Corrective lens user	3/36 (8.3%)	3	8/33 (24.2%)	8
Orthodontic appliance user	9/36 (25%)	9	7/33 (21.2%)	7
Surgical and medical procedures
Adenoidectomy	2/36 (5.6%)	2	0/33 (0%)	0
Ear tube insertion	4/36 (11.1%)	5	5/33 (15.2%)	7
Mole excision	6/36 (16.7%)	6	2/33 (6.1%)	2
Oral surgery	2/36 (5.6%)	2	0/33 (0%)	0
Orthodontic procedure	4/36 (11.1%)	4	7/33 (21.2%)	7
Palatal operation	3/36 (8.3%)	3	0/33 (0%)	0
Tooth extraction	2/36 (5.6%)	2	2/33 (6.1%)	2
Tympanoplasty	5/36 (13.9%)	5	3/33 (9.1%)	3
Wisdom teeth removal	2/36 (5.6%)	2	1/33 (3%)	1
Vascular disorders
Aortic dilatation	0/36 (0%)	0	3/33 (9.1%)	3
Hypertension	1/36 (2.8%)	1	2/33 (6.1%)	2
Lymphoedema	3/36 (8.3%)	3	1/33 (3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.