Trial Outcomes & Findings for Somatropin Treatment to Final Height in Turner Syndrome (NCT NCT00191113)
NCT ID: NCT00191113
Last Updated: 2010-01-27
Results Overview
Value analyzed is change from baseline to the most mature height measurement available. The terms Standard Deviation Score (SDS) and National Center for Health Statistics (NCHS) were defined in baseline characteristics. Greater height SDS values indicate greater height; positive values of change from baseline indicate increased height.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
154 participants
Primary outcome timeframe
Baseline, and end of 4-year addendum
Results posted on
2010-01-27
Participant Flow
Addenda 1, 2, and 3 are not sequential, and they differ in eligibility criteria. Depending on individual eligibility and choices made, a patient might have participated in none, 1, 2, or all 3 of these addenda.
Addendum 1: provided option of Humatrope treatment to patients who had been randomized to control in Core Study. Addendum 2: extended period of follow-up for 5 years after discontinuation from Core Study. Addendum 3: evaluated possible genomic imprinting effects (published: Hamelin et al. 2006).
Participant milestones
| Measure |
As-Randomized Control
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Core Study
STARTED
|
78
|
76
|
|
Core Study
COMPLETED
|
43
|
61
|
|
Core Study
NOT COMPLETED
|
35
|
15
|
|
Addendum 1
STARTED
|
2
|
0
|
|
Addendum 1
COMPLETED
|
2
|
0
|
|
Addendum 1
NOT COMPLETED
|
0
|
0
|
|
Addendum 2
STARTED
|
28
|
48
|
|
Addendum 2
COMPLETED
|
18
|
31
|
|
Addendum 2
NOT COMPLETED
|
10
|
17
|
|
Addendum 3
STARTED
|
20
|
37
|
|
Addendum 3
COMPLETED
|
20
|
37
|
|
Addendum 3
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
As-Randomized Control
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Core Study
Withdrawal by Subject
|
25
|
9
|
|
Core Study
Protocol Violation
|
6
|
2
|
|
Core Study
Lost to Follow-up
|
3
|
0
|
|
Core Study
Adverse Event
|
0
|
2
|
|
Core Study
Lack of Efficacy
|
0
|
2
|
|
Core Study
Death
|
1
|
0
|
Baseline Characteristics
Somatropin Treatment to Final Height in Turner Syndrome
Baseline characteristics by cohort
| Measure |
As-Randomized Control
n=78 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=76 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
Total
n=154 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
10.46 years
STANDARD_DEVIATION 1.77 • n=5 Participants
|
10.36 years
STANDARD_DEVIATION 1.80 • n=7 Participants
|
10.41 years
STANDARD_DEVIATION 1.78 • n=5 Participants
|
|
Sex: Female, Male
Female
|
78 Participants
n=5 Participants
|
76 Participants
n=7 Participants
|
154 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
78 participants
n=5 Participants
|
76 participants
n=7 Participants
|
154 participants
n=5 Participants
|
|
Karyotype
45,X
|
48 participants
n=5 Participants
|
45 participants
n=7 Participants
|
93 participants
n=5 Participants
|
|
Karyotype
45,X/46,XXqi
|
6 participants
n=5 Participants
|
2 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Karyotype
45,X/46,XXr
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Karyotype
45,X/46,XX
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Karyotype
46,XXqi
|
2 participants
n=5 Participants
|
6 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Karyotype
45,X/47,XXX
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Karyotype
46,XXp
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Karyotype
45,X/46,XXp
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Karyotype
45,X/46,XX/47,XXX
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Karyotype
46,XXr
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Karyotype
Other
|
15 participants
n=5 Participants
|
15 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
Race/Ethnicity
American Indian or Alaska Native
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity
Asian
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Race/Ethnicity
Native Hawaiian or Other Pacific Islander
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity
Black or African American
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity
White
|
54 participants
n=5 Participants
|
66 participants
n=7 Participants
|
120 participants
n=5 Participants
|
|
Race/Ethnicity
Hispanic
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity
Other
|
4 participants
n=5 Participants
|
0 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Race/Ethnicity
Unknown
|
11 participants
n=5 Participants
|
1 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Bone Age
|
8.57 years
STANDARD_DEVIATION 1.51 • n=5 Participants
|
8.79 years
STANDARD_DEVIATION 1.42 • n=7 Participants
|
8.69 years
STANDARD_DEVIATION 1.46 • n=5 Participants
|
|
Height
|
120.06 centimeters
STANDARD_DEVIATION 8.26 • n=5 Participants
|
119.84 centimeters
STANDARD_DEVIATION 8.45 • n=7 Participants
|
119.96 centimeters
STANDARD_DEVIATION 8.33 • n=5 Participants
|
|
Height Standard Deviation Score (SDS) [Lyon]
|
-0.13 Standard Deviation Score (SDS)
STANDARD_DEVIATION 0.86 • n=5 Participants
|
-0.10 Standard Deviation Score (SDS)
STANDARD_DEVIATION 0.88 • n=7 Participants
|
-0.11 Standard Deviation Score (SDS)
STANDARD_DEVIATION 0.87 • n=5 Participants
|
|
Height Standard Deviation Score (SDS) [National Center for Health Statistics (NCHS)]
|
-3.25 Standard Deviation Score (SDS)
STANDARD_DEVIATION 0.82 • n=5 Participants
|
-3.21 Standard Deviation Score (SDS)
STANDARD_DEVIATION 0.82 • n=7 Participants
|
-3.23 Standard Deviation Score (SDS)
STANDARD_DEVIATION 0.82 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, and end of 4-year addendumPopulation: Population of all randomized patients. Intent to treat analysis with as-randomized treatment groups, at most mature measurement available.
Value analyzed is change from baseline to the most mature height measurement available. The terms Standard Deviation Score (SDS) and National Center for Health Statistics (NCHS) were defined in baseline characteristics. Greater height SDS values indicate greater height; positive values of change from baseline indicate increased height.
Outcome measures
| Measure |
As-Randomized Control
n=78 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=76 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline to Last Measurement, As Randomized Population
|
0.09 Standard Deviation Score (SDS) [NCHS]
Standard Error 0.07
|
0.97 Standard Deviation Score (SDS) [NCHS]
Standard Error 0.07
|
PRIMARY outcome
Timeframe: at completion of core study, or at end of 4-year addendumPopulation: Population of patients for whom Final Height measurements are available. Efficacy analysis with as-treated treatment groups, at most mature measurement available at or after attainment of Final Height.
SDS report the number of standard deviations from the mean for age and sex for an individual measurement (normal range: -2 to +2 SDS). Height SDS \[NCHS\] uses the NCHS US general female population reference height values for age (Kuczmarski RJ et al. 2000) as the population mean and standard deviation. Calculation of Height SDS is provided in Height SDS \[Lyon\] description (Baseline). Since data reported by Kuczmarski RJ et al provides US general female population standards, values of Height SDS \[NCHS\] for untreated patients with Turner syndrome tend to be below zero e.g, -2.0 to -4.0 SDS.
Outcome measures
| Measure |
As-Randomized Control
n=48 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=82 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Last Measurement After Attainment of Final Height
|
-3.30 Standard Deviation Score (SDS) [NCHS]
Standard Error 0.07
|
-2.25 Standard Deviation Score (SDS) [NCHS]
Standard Error 0.05
|
SECONDARY outcome
Timeframe: every 3 months during core study, and at start and end of 4-year addendumValue analyzed is change from baseline to the most mature height measurement available. The terms Standard Deviation Score (SDS) and National Center for Health Statistics (NCHS) were defined in baseline characteristics. Greater height SDS values indicate greater height; positive values of change from baseline indicate increased height.
Outcome measures
| Measure |
As-Randomized Control
n=48 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=82 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline, As-Treated Population
|
-0.09 Standard Deviation Score (SDS) [NCHS]
Standard Error 0.08
|
0.99 Standard Deviation Score (SDS) [NCHS]
Standard Error 0.06
|
SECONDARY outcome
Timeframe: every 3 months during core study, and at start and end of 4-year addendumMost mature measurement available, at or after attainment of Final Height.
Outcome measures
| Measure |
As-Randomized Control
n=48 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=82 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Height (Centimeters [cm])
|
141.63 centimeters (cm)
Standard Error 0.47
|
148.52 centimeters (cm)
Standard Error 0.36
|
SECONDARY outcome
Timeframe: at completion of core study or beginning of addendumPopulation: All Randomized Patients with Hearing Examination
Outcome measures
| Measure |
As-Randomized Control
n=19 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=53 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Number of Participants With an Abnormal Pure Tone Audiometry, Audiologist Assessment
|
10 participants
|
29 participants
|
SECONDARY outcome
Timeframe: at completion of core study or beginning of addendumPopulation: All Randomized Patients with Hearing Examination
Outcome measures
| Measure |
As-Randomized Control
n=19 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=53 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Number of Participants With Abnormal Speech Audiometry, Audiologist Assessment
|
3 participants
|
12 participants
|
SECONDARY outcome
Timeframe: at completion of core study or beginning of addendumPopulation: All Randomized Patients with Hearing Examination
Outcome measures
| Measure |
As-Randomized Control
n=19 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=53 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Number of Participants With Abnormal Impedance Tympanometry, Audiologist Assessment
|
2 participants
|
18 participants
|
SECONDARY outcome
Timeframe: at completion of core study or beginning of addendumPopulation: All Randomized Patients with Hearing Examination for whom Audiologist responded to Hearing Loss question
Sensorineural Hearing Loss (SNHL)=air conduction threshold \>20 dB HL and air-bone gap ≤10 dB HL; Conductive Hearing Loss (CHL)= air conduction threshold \>20 dB HL, bone conduction threshold ≤20 dB HL and air-bone gap \>10 dB HL; Mixed Hearing Loss (MHL) = evidence of SNHL as defined above and CHL as defined above, in the same ear; Unspecified Hearing Loss (UHL)= abnormal hearing with none of SNHL, CHL, or MHL present.
Outcome measures
| Measure |
As-Randomized Control
n=19 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=52 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Number of Participants With Hearing Loss, Audiologist Assessment
Sensorineural Hearing Loss
|
8 participants
|
15 participants
|
|
Number of Participants With Hearing Loss, Audiologist Assessment
Mixed Hearing Loss
|
2 participants
|
9 participants
|
|
Number of Participants With Hearing Loss, Audiologist Assessment
Conductive Hearing Loss
|
1 participants
|
7 participants
|
|
Number of Participants With Hearing Loss, Audiologist Assessment
Unspecified Hearing Loss
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: At core study baseline, and at end of 4-year addendumPopulation: Patients who were followed for at least 4 years without growth hormone treatment or who received growth hormone for at least 4 years, and who were treated as randomized and had core study baseline and addendum glucose metabolism data.
Change from core study baseline to addendum 2 maximum.
Outcome measures
| Measure |
As-Randomized Control
n=20 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=36 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Fasting Glucose, Change From Baseline
|
5.495 mg / dL
Standard Error 2.455
|
3.003 mg / dL
Standard Error 1.830
|
SECONDARY outcome
Timeframe: At start and through end of 4-year addendum (up to an additional 2 years)Population: Patients with addendum data who were followed for at least 4 years without growth hormone treatment (and never received growth hormone) or who received growth hormone for at least 4 years.
Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Outcome measures
| Measure |
As-Randomized Control
n=21 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=39 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Maximum Fasting Glucose Value
|
85.2 milligrams per deciliter (mg/dL)
Standard Deviation 6.6
|
85.2 milligrams per deciliter (mg/dL)
Standard Deviation 10.4
|
SECONDARY outcome
Timeframe: At start and through end of 4-year addendumPopulation: Patients with any Addendum 2 glucose metabolism data
Indicates if patient had any measured value exceeding threshold of normality at any visit during addendum. Abnormal Fasting Glucose=Fasting Glucose \>=100 milligrams per deciliter (mg/dL).
Outcome measures
| Measure |
As-Randomized Control
n=21 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=39 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Number of Participants With Any Abnormal Fasting Glucose Value
|
0 participants
|
3 participants
|
SECONDARY outcome
Timeframe: At start and through end of 4-year addendum (up to an additional 2 years)Population: Patients with addendum data who were followed for at least 4 years without growth hormone treatment (and never received growth hormone) or who received growth hormone for at least 4 years.
Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Outcome measures
| Measure |
As-Randomized Control
n=21 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=40 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Maximum Fasting Insulin Values
|
9.5 micro International Units per milliliter
Standard Deviation 10.8
|
9.7 micro International Units per milliliter
Standard Deviation 9.3
|
SECONDARY outcome
Timeframe: At start and through end of 4-year addendumPopulation: Patients with any Addendum 2 glucose metabolism data
Indicates if patient had any measured value exceeding threshold of normality at any visit during addendum. Abnormal Fasting Insulin = Fasting Insulin \>=35 micro International Units per milliliter (uIU/mL).
Outcome measures
| Measure |
As-Randomized Control
n=21 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=40 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Number of Participants With Any Abnormal Fasting Insulin Value
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: At start and through end of 4-year addendum (up to an additional 2 years)Population: Patients with addendum data who were followed for at least 4 years without growth hormone treatment (and never received growth hormone) or who received growth hormone for at least 4 years.
Minimum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Outcome measures
| Measure |
As-Randomized Control
n=21 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=38 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Minimum Fasting Glucose/Insulin Ratio Values
|
12.5 milligrams per 10^-4 Units (mg/[10^-4]U)
Standard Deviation 6.0
|
12.2 milligrams per 10^-4 Units (mg/[10^-4]U)
Standard Deviation 5.3
|
SECONDARY outcome
Timeframe: At start and through end of 4-year addendumPopulation: Patients with any Addendum 2 glucose metabolism data. Calculated only for patients with fasting blood \<100 mg/dL.
Indicates if patient had any measured value below threshold of normality at any visit during addendum. Abnormal Fasting Glucose/Insulin Ratio = Fasting Glucose/Insulin Ratio \<=4.5 milligrams per 10\^-4 Units (mg/10\^-4U).
Outcome measures
| Measure |
As-Randomized Control
n=21 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=38 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Number of Participants With Any Abnormal Fasting Glucose/Insulin Ratio Value
|
1 participants
|
3 participants
|
SECONDARY outcome
Timeframe: At core study baseline, and at end of 4-year addendumPopulation: Patients who were followed for at least 4 years without growth hormone treatment or who received growth hormone for at least 4 years, and who were treated as randomized and had core study baseline and addendum glucose metabolism data.
Change from core study baseline to addendum 2 maximum.
Outcome measures
| Measure |
As-Randomized Control
n=20 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=36 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Glycosylated Hemoglobin, Change From Baseline
|
0.215 percent (%)
Standard Error 0.077
|
0.208 percent (%)
Standard Error 0.057
|
SECONDARY outcome
Timeframe: At start and through end of 4-year addendum (up to an additional 2 years)Population: Patients with addendum data who were followed for at least 4 years without growth hormone treatment (and never received growth hormone) or who received growth hormone for at least 4 years.
Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Outcome measures
| Measure |
As-Randomized Control
n=21 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=40 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Maximum Glycosylated Hemoglobin
|
5.0 percent (%)
Standard Deviation 0.5
|
5.0 percent (%)
Standard Deviation 0.4
|
SECONDARY outcome
Timeframe: At start and through end of 4-year addendumPopulation: Patients with any Addendum 2 glucose metabolism data.
Indicates if patient had any measured value exceeding threshold of normality at any visit during addendum. Abnormal Glycosylated Hemoglobin = HbA1c ≥6.8% (up until 11-May-1998); and then HbA1c ≥6.1% (from 19-May-1998 onwards).
Outcome measures
| Measure |
As-Randomized Control
n=21 Participants
Control arm; untreated with Humatrope. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
As-Randomized Humatrope
n=40 Participants
Humatrope (0.05 mg/kg/dose) by subcutaneous injection 6 times per week. Ethinyl estradiol (escalating doses to 20 mcg daily) after age 13, and medroxyprogesterone acetate (10 mg tablets ten days monthly) after age 15. Subject continues until Core study completion criteria are met (protocol final height).
|
|---|---|---|
|
Number of Participants With Any Abnormal Glycosylated Hemoglobin (HbA1c) Value
|
0 participants
|
0 participants
|
Adverse Events
Treated-As-Randomized Control
Serious events: 10 serious events
Other events: 53 other events
Deaths: 0 deaths
Treated-As-Randomized Humatrope
Serious events: 22 serious events
Other events: 74 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treated-As-Randomized Control
n=54 participants at risk
Patients in the As-Randomized Control group who at each observed time point remained untreated with growth hormone.
|
Treated-As-Randomized Humatrope
n=74 participants at risk
Patients in the As-Randomized Humatrope group who received Humatrope
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia iron deficiency
|
0.00%
0/54
|
1.4%
1/74
|
|
Blood and lymphatic system disorders
Hypochromic microcytic anemia
|
0.00%
0/54
|
1.4%
1/74
|
|
Blood and lymphatic system disorders
Idiopathic thrombocytopenic purpura
|
1.9%
1/54
|
0.00%
0/74
|
|
Cardiac disorders
Cardiac arrest
|
1.9%
1/54
|
0.00%
0/74
|
|
Infections and infestations
Cellulitis of foot
|
0.00%
0/54
|
1.4%
1/74
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/54
|
1.4%
1/74
|
|
Infections and infestations
Otitis media
|
0.00%
0/54
|
1.4%
1/74
|
|
Infections and infestations
Pneumonia
|
1.9%
1/54
|
0.00%
0/74
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/54
|
1.4%
1/74
|
|
Infections and infestations
Stomach flu
|
0.00%
0/54
|
1.4%
1/74
|
|
Infections and infestations
Viral meningitis
|
0.00%
0/54
|
1.4%
1/74
|
|
Injury, poisoning and procedural complications
Arm fracture
|
0.00%
0/54
|
2.7%
2/74
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.00%
0/54
|
1.4%
1/74
|
|
Investigations
Colonoscopy
|
0.00%
0/54
|
1.4%
1/74
|
|
Investigations
Cystoscopy
|
0.00%
0/54
|
1.4%
1/74
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/54
|
1.4%
1/74
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm benign
|
0.00%
0/54
|
1.4%
1/74
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
0.00%
0/54
|
1.4%
1/74
|
|
Skin and subcutaneous tissue disorders
Pustular psoriasis
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Adenoidectomy
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Aorta coarctation repair
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Appendectomy
|
3.7%
2/54
|
0.00%
0/74
|
|
Surgical and medical procedures
Chest wall repair
|
1.9%
1/54
|
0.00%
0/74
|
|
Surgical and medical procedures
Cholesteatoma removal
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Dental surgery NOS
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Eye muscle operation
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Heart valve operation
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Mastoid operation
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Mastoidectomy
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Orchiectomy
|
0.00%
0/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Pterygium operation
|
1.9%
1/54
|
1.4%
1/74
|
|
Surgical and medical procedures
Scar removal
|
1.9%
1/54
|
0.00%
0/74
|
|
Surgical and medical procedures
Surgical procedure
|
1.9%
1/54
|
0.00%
0/74
|
|
Surgical and medical procedures
Tooth extraction
|
1.9%
1/54
|
0.00%
0/74
|
|
Surgical and medical procedures
Tympanoplasty
|
0.00%
0/54
|
4.1%
3/74
|
|
Vascular disorders
Aortic aneurysm rupture
|
1.9%
1/54
|
0.00%
0/74
|
|
Vascular disorders
Thrombophlebitis
|
1.9%
1/54
|
0.00%
0/74
|
Other adverse events
| Measure |
Treated-As-Randomized Control
n=54 participants at risk
Patients in the As-Randomized Control group who at each observed time point remained untreated with growth hormone.
|
Treated-As-Randomized Humatrope
n=74 participants at risk
Patients in the As-Randomized Humatrope group who received Humatrope
|
|---|---|---|
|
Ear and labyrinth disorders
Ear ache
|
11.1%
6/54
|
13.5%
10/74
|
|
Ear and labyrinth disorders
Ear discharge
|
0.00%
0/54
|
5.4%
4/74
|
|
Ear and labyrinth disorders
Ear pain
|
5.6%
3/54
|
18.9%
14/74
|
|
Ear and labyrinth disorders
Earache
|
9.3%
5/54
|
10.8%
8/74
|
|
Ear and labyrinth disorders
Hearing loss
|
3.7%
2/54
|
9.5%
7/74
|
|
Ear and labyrinth disorders
Sensorineural hearing loss
|
5.6%
3/54
|
0.00%
0/74
|
|
Ear and labyrinth disorders
Tympanosclerosis
|
5.6%
3/54
|
0.00%
0/74
|
|
Endocrine disorders
Hypothyroidism
|
13.0%
7/54
|
17.6%
13/74
|
|
Eye disorders
Conjunctivitis
|
3.7%
2/54
|
5.4%
4/74
|
|
Eye disorders
Myopia
|
5.6%
3/54
|
5.4%
4/74
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
9/54
|
12.2%
9/74
|
|
Gastrointestinal disorders
Ache stomach
|
0.00%
0/54
|
5.4%
4/74
|
|
Gastrointestinal disorders
Diarrhea
|
20.4%
11/54
|
16.2%
12/74
|
|
Gastrointestinal disorders
Nausea
|
9.3%
5/54
|
17.6%
13/74
|
|
Gastrointestinal disorders
Stomach ache
|
13.0%
7/54
|
9.5%
7/74
|
|
Gastrointestinal disorders
Stomach cramps
|
7.4%
4/54
|
5.4%
4/74
|
|
Gastrointestinal disorders
Stomach pain
|
3.7%
2/54
|
8.1%
6/74
|
|
Gastrointestinal disorders
Upset stomach
|
5.6%
3/54
|
6.8%
5/74
|
|
Gastrointestinal disorders
Vomiting
|
38.9%
21/54
|
39.2%
29/74
|
|
General disorders
Chest pain
|
7.4%
4/54
|
1.4%
1/74
|
|
General disorders
Fatigue
|
7.4%
4/54
|
1.4%
1/74
|
|
General disorders
Fever
|
37.0%
20/54
|
48.6%
36/74
|
|
General disorders
Pain
|
0.00%
0/54
|
5.4%
4/74
|
|
Immune system disorders
Hay fever
|
1.9%
1/54
|
9.5%
7/74
|
|
Immune system disorders
Multiple allergies
|
1.9%
1/54
|
8.1%
6/74
|
|
Infections and infestations
Bladder infection
|
5.6%
3/54
|
5.4%
4/74
|
|
Infections and infestations
Bronchitis
|
9.3%
5/54
|
9.5%
7/74
|
|
Infections and infestations
Chest cold
|
0.00%
0/54
|
9.5%
7/74
|
|
Infections and infestations
Chickenpox
|
9.3%
5/54
|
10.8%
8/74
|
|
Infections and infestations
Cold
|
72.2%
39/54
|
56.8%
42/74
|
|
Infections and infestations
Cold symptoms
|
7.4%
4/54
|
9.5%
7/74
|
|
Infections and infestations
Common cold
|
7.4%
4/54
|
6.8%
5/74
|
|
Infections and infestations
Ear infection
|
22.2%
12/54
|
36.5%
27/74
|
|
Infections and infestations
Eye infection
|
5.6%
3/54
|
12.2%
9/74
|
|
Infections and infestations
Flu
|
37.0%
20/54
|
48.6%
36/74
|
|
Infections and infestations
Flu syndrome
|
11.1%
6/54
|
20.3%
15/74
|
|
Infections and infestations
Gastroenteritis
|
3.7%
2/54
|
8.1%
6/74
|
|
Infections and infestations
Head cold
|
16.7%
9/54
|
24.3%
18/74
|
|
Infections and infestations
Impetigo
|
7.4%
4/54
|
8.1%
6/74
|
|
Infections and infestations
Otitis externa
|
11.1%
6/54
|
17.6%
13/74
|
|
Infections and infestations
Otitis media
|
24.1%
13/54
|
41.9%
31/74
|
|
Infections and infestations
Pharyngitis
|
14.8%
8/54
|
14.9%
11/74
|
|
Infections and infestations
Rhinitis
|
20.4%
11/54
|
23.0%
17/74
|
|
Infections and infestations
Sinus infection
|
1.9%
1/54
|
6.8%
5/74
|
|
Infections and infestations
Sinusitis
|
5.6%
3/54
|
9.5%
7/74
|
|
Infections and infestations
Stomach flu
|
11.1%
6/54
|
8.1%
6/74
|
|
Infections and infestations
Streptococcal sore throat
|
7.4%
4/54
|
12.2%
9/74
|
|
Infections and infestations
Throat infection
|
13.0%
7/54
|
10.8%
8/74
|
|
Infections and infestations
Tonsillitis
|
9.3%
5/54
|
8.1%
6/74
|
|
Infections and infestations
Upper respiratory infection
|
25.9%
14/54
|
17.6%
13/74
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
9/54
|
10.8%
8/74
|
|
Infections and infestations
Urinary tract infection
|
5.6%
3/54
|
6.8%
5/74
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/54
|
6.8%
5/74
|
|
Injury, poisoning and procedural complications
Head injury
|
5.6%
3/54
|
2.7%
2/74
|
|
Musculoskeletal and connective tissue disorders
Knee pain
|
1.9%
1/54
|
10.8%
8/74
|
|
Musculoskeletal and connective tissue disorders
Leg pain
|
1.9%
1/54
|
5.4%
4/74
|
|
Musculoskeletal and connective tissue disorders
Low back pain
|
7.4%
4/54
|
4.1%
3/74
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
7.4%
4/54
|
2.7%
2/74
|
|
Musculoskeletal and connective tissue disorders
Scoliosis
|
14.8%
8/54
|
8.1%
6/74
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Naevus
|
3.7%
2/54
|
6.8%
5/74
|
|
Nervous system disorders
Dizziness
|
7.4%
4/54
|
9.5%
7/74
|
|
Nervous system disorders
Headache
|
46.3%
25/54
|
62.2%
46/74
|
|
Nervous system disorders
Intermittent headache
|
5.6%
3/54
|
16.2%
12/74
|
|
Psychiatric disorders
Depression
|
7.4%
4/54
|
8.1%
6/74
|
|
Reproductive system and breast disorders
Cramps menstrual
|
3.7%
2/54
|
5.4%
4/74
|
|
Reproductive system and breast disorders
Dysmenorrhea
|
3.7%
2/54
|
5.4%
4/74
|
|
Reproductive system and breast disorders
Menstrual cramps
|
13.0%
7/54
|
9.5%
7/74
|
|
Reproductive system and breast disorders
Primary ovarian failure
|
7.4%
4/54
|
6.8%
5/74
|
|
Reproductive system and breast disorders
Spotting vaginal
|
7.4%
4/54
|
0.00%
0/74
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/54
|
5.4%
4/74
|
|
Respiratory, thoracic and mediastinal disorders
Congestion nasal
|
3.7%
2/54
|
6.8%
5/74
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.9%
14/54
|
36.5%
27/74
|
|
Respiratory, thoracic and mediastinal disorders
Coughing
|
3.7%
2/54
|
6.8%
5/74
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.6%
3/54
|
2.7%
2/74
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
14.8%
8/54
|
23.0%
17/74
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discharge
|
5.6%
3/54
|
2.7%
2/74
|
|
Respiratory, thoracic and mediastinal disorders
Nose bleed
|
1.9%
1/54
|
6.8%
5/74
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
9.3%
5/54
|
9.5%
7/74
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
51.9%
28/54
|
50.0%
37/74
|
|
Respiratory, thoracic and mediastinal disorders
Throat sore
|
1.9%
1/54
|
8.1%
6/74
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
1.9%
1/54
|
10.8%
8/74
|
|
Skin and subcutaneous tissue disorders
Eczema
|
7.4%
4/54
|
5.4%
4/74
|
|
Skin and subcutaneous tissue disorders
Ingrown toe nail
|
5.6%
3/54
|
2.7%
2/74
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.8%
8/54
|
10.8%
8/74
|
|
Surgical and medical procedures
Dental surgery NOS
|
1.9%
1/54
|
5.4%
4/74
|
|
Surgical and medical procedures
Dental treatment
|
14.8%
8/54
|
8.1%
6/74
|
|
Surgical and medical procedures
Ear tube insertion
|
1.9%
1/54
|
5.4%
4/74
|
|
Surgical and medical procedures
Mole excision
|
3.7%
2/54
|
6.8%
5/74
|
|
Surgical and medical procedures
Myringotomy
|
1.9%
1/54
|
10.8%
8/74
|
|
Surgical and medical procedures
Tooth extraction
|
5.6%
3/54
|
4.1%
3/74
|
|
Surgical and medical procedures
Tympanoplasty
|
0.00%
0/54
|
5.4%
4/74
|
|
Vascular disorders
Aortic dilatation
|
5.6%
3/54
|
1.4%
1/74
|
|
Vascular disorders
Blood pressure high
|
5.6%
3/54
|
1.4%
1/74
|
|
Vascular disorders
Hypertension
|
1.9%
1/54
|
9.5%
7/74
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 1-800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60