Turner Syndrome
Conditions
Keywords
syndrome, Turner, Turner's, height, growth, growth hormone, somatropin, short stature, short, hearing, glucose metabolism
Brief summary
A randomized, controlled trial in girls with Turner syndrome at least 7 years old and younger than 13 at study entry, to determine the efficacy and safety of Humatrope (somatropin) treatment in promoting linear growth to final height.
Detailed description
A randomized, controlled trial of Humatrope (somatropin) treatment in girls with Turner syndrome at least 7 years old and younger than 13 at study entry. Core study objectives are to determine the efficacy of Humatrope in promoting linear growth to final height in girls with Turner syndrome, and to assess the safety of this treatment. Core study completion criteria (protocol final height) are that the patient has both a height velocity \< 2 cm per year and a bone age of 14 years or greater. Addendum 1 provides the option of Humatrope treatment to patients who were randomized to the Control arm of the Core study and who discontinued from the study on or after December 19, 1997. Addendum 2 objectives are: 1) to collect true final height data; 2) to evaluate hearing, tympanic membrane function and other specific areas of interest with respect to the safety of growth hormone therapy in Turner syndrome; 3) to evaluate pancreatic beta cell function (glucose metabolism) in patients previously enrolled in the Core study. Addendum 3 objective is to determine the parental origin of the retained X chromosome of an appropriate subset of patients currently or previously enrolled in the Core study, and to determine whether this parental origin holds any predictive value for spontaneous growth or for response to growth hormone therapy.
Interventions
DRUGSomatropin
0.05 mg/kg/dose by subcutaneous injection 6 times per week, until Core study completion criteria are met (protocol final height).
escalating doses 2.5-20.0 mcg tablets daily after age 13 and at least one year on study, continuing until Core study completion criteria are met.
DRUGMedroxyprogesterone acetate
10 mg tablets, ten days monthly, after age 15, continuing until Core study completion criteria are met.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
7 Years to 13 Years
Healthy volunteers
No
Inclusion criteria
* girl with Turner syndrome * prepubertal, Tanner stage I breast * height velocity less than 6 cm/year and height less than or equal to the tenth percentile for sex and age in general population * at least 6 months (preferably 12 months) of accurate height measurements available for calculation of pre-study height velocity * if thyroxine deficient, to have received replacement therapy, and for six months prior to enrollment have had normal thyroid function tests
Exclusion criteria
* prior treatment with growth hormone * presence of a Y component in karyotype with gonads in situ * diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline to Last Measurement, As Randomized Population | Baseline, and end of 4-year addendum | 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. |
| Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Last Measurement After Attainment of Final Height | at completion of core study, or at end of 4-year addendum | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Abnormal Fasting Glucose Value | At start and through end of 4-year addendum | 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). |
| Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline, As-Treated Population | every 3 months during core study, and at start and end of 4-year addendum | 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. |
| Height (Centimeters [cm]) | every 3 months during core study, and at start and end of 4-year addendum | Most mature measurement available, at or after attainment of Final Height. |
| Number of Participants With an Abnormal Pure Tone Audiometry, Audiologist Assessment | at completion of core study or beginning of addendum | — |
| Number of Participants With Abnormal Speech Audiometry, Audiologist Assessment | at completion of core study or beginning of addendum | — |
| Number of Participants With Abnormal Impedance Tympanometry, Audiologist Assessment | at completion of core study or beginning of addendum | — |
| Number of Participants With Hearing Loss, Audiologist Assessment | at completion of core study or beginning of addendum | 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. |
| Maximum Fasting Insulin Values | At start and through end of 4-year addendum (up to an additional 2 years) | Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years. |
| Number of Participants With Any Abnormal Fasting Insulin Value | At start and through end of 4-year addendum | 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). |
| Minimum Fasting Glucose/Insulin Ratio Values | At start and through end of 4-year addendum (up to an additional 2 years) | Minimum measured value over addendum. In special cases an additional measurement is taken at 2 years. |
| Number of Participants With Any Abnormal Fasting Glucose/Insulin Ratio Value | At start and through end of 4-year addendum | 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). |
| Glycosylated Hemoglobin, Change From Baseline | At core study baseline, and at end of 4-year addendum | Change from core study baseline to addendum 2 maximum. |
| Maximum Glycosylated Hemoglobin | At start and through end of 4-year addendum (up to an additional 2 years) | Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years. |
| Number of Participants With Any Abnormal Glycosylated Hemoglobin (HbA1c) Value | At start and through end of 4-year addendum | 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). |
| Fasting Glucose, Change From Baseline | At core study baseline, and at end of 4-year addendum | Change from core study baseline to addendum 2 maximum. |
| Maximum Fasting Glucose Value | At start and through end of 4-year addendum (up to an additional 2 years) | Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years. |
Countries
Canada
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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). | 78 |
| 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). | 76 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core Study | Adverse Event | 0 | 2 |
| Core Study | Death | 1 | 0 |
| Core Study | Lack of Efficacy | 0 | 2 |
| Core Study | Lost to Follow-up | 3 | 0 |
| Core Study | Protocol Violation | 6 | 2 |
| Core Study | Withdrawal by Subject | 25 | 9 |
Baseline characteristics
| Characteristic | As-Randomized Humatrope | Total | As-Randomized Control |
|---|---|---|---|
| Age Continuous | 10.36 years STANDARD_DEVIATION 1.8 | 10.41 years STANDARD_DEVIATION 1.78 | 10.46 years STANDARD_DEVIATION 1.77 |
| Bone Age | 8.79 years STANDARD_DEVIATION 1.42 | 8.69 years STANDARD_DEVIATION 1.46 | 8.57 years STANDARD_DEVIATION 1.51 |
| Height | 119.84 centimeters STANDARD_DEVIATION 8.45 | 119.96 centimeters STANDARD_DEVIATION 8.33 | 120.06 centimeters STANDARD_DEVIATION 8.26 |
| Height Standard Deviation Score (SDS) [Lyon] | -0.10 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.88 | -0.11 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.87 | -0.13 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.86 |
| Height Standard Deviation Score (SDS) [National Center for Health Statistics (NCHS)] | -3.21 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.82 | -3.23 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.82 | -3.25 Standard Deviation Score (SDS) STANDARD_DEVIATION 0.82 |
| Karyotype 45,X | 45 participants | 93 participants | 48 participants |
| Karyotype 45,X/46,XX | 3 participants | 6 participants | 3 participants |
| Karyotype 45,X/46,XX/47,XXX | 0 participants | 0 participants | 0 participants |
| Karyotype 45,X/46,XXp | 1 participants | 2 participants | 1 participants |
| Karyotype 45,X/46,XXqi | 2 participants | 8 participants | 6 participants |
| Karyotype 45,X/46,XXr | 2 participants | 3 participants | 1 participants |
| Karyotype 45,X/47,XXX | 2 participants | 3 participants | 1 participants |
| Karyotype 46,XXp | 0 participants | 1 participants | 1 participants |
| Karyotype 46,XXqi | 6 participants | 8 participants | 2 participants |
| Karyotype 46,XXr | 0 participants | 0 participants | 0 participants |
| Karyotype Other | 15 participants | 30 participants | 15 participants |
| Race/Ethnicity American Indian or Alaska Native | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity Asian | 6 participants | 13 participants | 7 participants |
| Race/Ethnicity Black or African American | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity Hispanic | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity Other | 0 participants | 4 participants | 4 participants |
| Race/Ethnicity Unknown | 1 participants | 12 participants | 11 participants |
| Race/Ethnicity White | 66 participants | 120 participants | 54 participants |
| Region of Enrollment Canada | 76 participants | 154 participants | 78 participants |
| Sex: Female, Male Female | 76 Participants | 154 Participants | 78 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 53 / 54 | 74 / 74 |
| serious Total, serious adverse events | 10 / 54 | 22 / 74 |
Outcome results
Primary
Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline to Last Measurement, As Randomized Population
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.
Time frame: Baseline, and end of 4-year addendum
Population: Population of all randomized patients. Intent to treat analysis with as-randomized treatment groups, at most mature measurement available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | 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 |
| As-Randomized Humatrope | Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline to Last Measurement, As Randomized Population | 0.97 Standard Deviation Score (SDS) [NCHS] | Standard Error 0.07 |
Comparison: This component of the primary analysis is inferential i.e. to ascertain definitively whether Humatrope treatment affects change in Height SDS (NCHS). Null hypothesis is no effect of Humatrope treatment.p-value: <0.00195% CI: [0.7, 1.1]ANCOVA
Primary
Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Last Measurement 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.
Time frame: at completion of core study, or at end of 4-year addendum
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | 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 |
| As-Randomized Humatrope | Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Last Measurement After Attainment of Final Height | -2.25 Standard Deviation Score (SDS) [NCHS] | Standard Error 0.05 |
Comparison: Estimation analysis of the magnitude of effect of treatment with growth hormone upon Final Height. Null hypothesis is no effect of growth hormone upon attained height standard deviation score (National Center for Health Statistics).p-value: <0.00195% CI: [0.9, 1.2]ANCOVA
Secondary
Fasting Glucose, Change From Baseline
Change from core study baseline to addendum 2 maximum.
Time frame: At core study baseline, and at end of 4-year addendum
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | Fasting Glucose, Change From Baseline | 5.495 mg / dL | Standard Error 2.455 |
| As-Randomized Humatrope | Fasting Glucose, Change From Baseline | 3.003 mg / dL | Standard Error 1.83 |
p-value: 0.41995% CI: [-8.631, 3.646]ANOVA
Secondary
Glycosylated Hemoglobin, Change From Baseline
Change from core study baseline to addendum 2 maximum.
Time frame: At core study baseline, and at end of 4-year addendum
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | Glycosylated Hemoglobin, Change From Baseline | 0.215 percent (%) | Standard Error 0.077 |
| As-Randomized Humatrope | Glycosylated Hemoglobin, Change From Baseline | 0.208 percent (%) | Standard Error 0.057 |
p-value: 0.94595% CI: [-0.199, 0.186]ANOVA
Secondary
Height (Centimeters [cm])
Most mature measurement available, at or after attainment of Final Height.
Time frame: every 3 months during core study, and at start and end of 4-year addendum
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | Height (Centimeters [cm]) | 141.63 centimeters (cm) | Standard Error 0.47 |
| As-Randomized Humatrope | Height (Centimeters [cm]) | 148.52 centimeters (cm) | Standard Error 0.36 |
p-value: <0.00195% CI: [5.7, 8.1]ANCOVA
Secondary
Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline, As-Treated Population
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.
Time frame: every 3 months during core study, and at start and end of 4-year addendum
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | 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 |
| As-Randomized Humatrope | Height Standard Deviation Score (SDS) (National Center for Health Statistics [NCHS]), Change From Baseline, As-Treated Population | 0.99 Standard Deviation Score (SDS) [NCHS] | Standard Error 0.06 |
p-value: <0.00195% CI: [0.9, 1.3]ANCOVA
Secondary
Maximum Fasting Glucose Value
Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | Maximum Fasting Glucose Value | 85.2 milligrams per deciliter (mg/dL) | Standard Deviation 6.6 |
| As-Randomized Humatrope | Maximum Fasting Glucose Value | 85.2 milligrams per deciliter (mg/dL) | Standard Deviation 10.4 |
Secondary
Maximum Fasting Insulin Values
Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | Maximum Fasting Insulin Values | 9.5 micro International Units per milliliter | Standard Deviation 10.8 |
| As-Randomized Humatrope | Maximum Fasting Insulin Values | 9.7 micro International Units per milliliter | Standard Deviation 9.3 |
Secondary
Maximum Glycosylated Hemoglobin
Maximum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | Maximum Glycosylated Hemoglobin | 5.0 percent (%) | Standard Deviation 0.5 |
| As-Randomized Humatrope | Maximum Glycosylated Hemoglobin | 5.0 percent (%) | Standard Deviation 0.4 |
Secondary
Minimum Fasting Glucose/Insulin Ratio Values
Minimum measured value over addendum. In special cases an additional measurement is taken at 2 years.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| As-Randomized Control | Minimum Fasting Glucose/Insulin Ratio Values | 12.5 milligrams per 10^-4 Units (mg/[10^-4]U) | Standard Deviation 6 |
| As-Randomized Humatrope | Minimum Fasting Glucose/Insulin Ratio Values | 12.2 milligrams per 10^-4 Units (mg/[10^-4]U) | Standard Deviation 5.3 |
Secondary
Number of Participants With Abnormal Impedance Tympanometry, Audiologist Assessment
Time frame: at completion of core study or beginning of addendum
Population: All Randomized Patients with Hearing Examination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| As-Randomized Control | Number of Participants With Abnormal Impedance Tympanometry, Audiologist Assessment | 2 participants |
| As-Randomized Humatrope | Number of Participants With Abnormal Impedance Tympanometry, Audiologist Assessment | 18 participants |
p-value: 0.073Fisher Exact
Secondary
Number of Participants With Abnormal Speech Audiometry, Audiologist Assessment
Time frame: at completion of core study or beginning of addendum
Population: All Randomized Patients with Hearing Examination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| As-Randomized Control | Number of Participants With Abnormal Speech Audiometry, Audiologist Assessment | 3 participants |
| As-Randomized Humatrope | Number of Participants With Abnormal Speech Audiometry, Audiologist Assessment | 12 participants |
p-value: 0.744Fisher Exact
Secondary
Number of Participants With an Abnormal Pure Tone Audiometry, Audiologist Assessment
Time frame: at completion of core study or beginning of addendum
Population: All Randomized Patients with Hearing Examination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| As-Randomized Control | Number of Participants With an Abnormal Pure Tone Audiometry, Audiologist Assessment | 10 participants |
| As-Randomized Humatrope | Number of Participants With an Abnormal Pure Tone Audiometry, Audiologist Assessment | 29 participants |
p-value: >0.999Fisher Exact
Secondary
Number of Participants With Any Abnormal Fasting Glucose/Insulin Ratio Value
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).
Time frame: At start and through end of 4-year addendum
Population: Patients with any Addendum 2 glucose metabolism data. Calculated only for patients with fasting blood \<100 mg/dL.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| As-Randomized Control | Number of Participants With Any Abnormal Fasting Glucose/Insulin Ratio Value | 1 participants |
| As-Randomized Humatrope | Number of Participants With Any Abnormal Fasting Glucose/Insulin Ratio Value | 3 participants |
p-value: >0.999Fisher Exact
Secondary
Number of Participants With Any Abnormal Fasting Glucose Value
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).
Time frame: At start and through end of 4-year addendum
Population: Patients with any Addendum 2 glucose metabolism data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| As-Randomized Control | Number of Participants With Any Abnormal Fasting Glucose Value | 0 participants |
| As-Randomized Humatrope | Number of Participants With Any Abnormal Fasting Glucose Value | 3 participants |
p-value: 0.545Fisher Exact
Secondary
Number of Participants With Any Abnormal Fasting Insulin Value
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).
Time frame: At start and through end of 4-year addendum
Population: Patients with any Addendum 2 glucose metabolism data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| As-Randomized Control | Number of Participants With Any Abnormal Fasting Insulin Value | 1 participants |
| As-Randomized Humatrope | Number of Participants With Any Abnormal Fasting Insulin Value | 2 participants |
p-value: >0.999Fisher Exact
Secondary
Number of Participants With Any Abnormal Glycosylated Hemoglobin (HbA1c) Value
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).
Time frame: At start and through end of 4-year addendum
Population: Patients with any Addendum 2 glucose metabolism data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| As-Randomized Control | Number of Participants With Any Abnormal Glycosylated Hemoglobin (HbA1c) Value | 0 participants |
| As-Randomized Humatrope | Number of Participants With Any Abnormal Glycosylated Hemoglobin (HbA1c) Value | 0 participants |
Fisher Exact
Secondary
Number of Participants With Hearing Loss, Audiologist Assessment
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.
Time frame: at completion of core study or beginning of addendum
Population: All Randomized Patients with Hearing Examination for whom Audiologist responded to Hearing Loss question
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| As-Randomized Control | Number of Participants With Hearing Loss, Audiologist Assessment | Conductive Hearing Loss | 1 participants |
| As-Randomized Control | Number of Participants With Hearing Loss, Audiologist Assessment | Mixed Hearing Loss | 2 participants |
| As-Randomized Control | Number of Participants With Hearing Loss, Audiologist Assessment | Unspecified Hearing Loss | 1 participants |
| As-Randomized Control | Number of Participants With Hearing Loss, Audiologist Assessment | Sensorineural Hearing Loss | 8 participants |
| As-Randomized Humatrope | Number of Participants With Hearing Loss, Audiologist Assessment | Unspecified Hearing Loss | 1 participants |
| As-Randomized Humatrope | Number of Participants With Hearing Loss, Audiologist Assessment | Conductive Hearing Loss | 7 participants |
| As-Randomized Humatrope | Number of Participants With Hearing Loss, Audiologist Assessment | Sensorineural Hearing Loss | 15 participants |
| As-Randomized Humatrope | Number of Participants With Hearing Loss, Audiologist Assessment | Mixed Hearing Loss | 9 participants |
Comparison: Comparison of proportion of patients with any category of hearing loss between As-Treated Growth Hormone group and As-Treated No Growth Hormone.p-value: >0.999Fisher Exact