Trial Outcomes & Findings for Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia (NCT NCT00001521)
NCT ID: NCT00001521
Last Updated: 2025-06-12
Results Overview
Adult height expressed in standard deviation score (SDS) units relative to the general population, with attainment of adult height defined as incremental growth \< 1.5 cm over 12 months. Adult height SDS was based on National Health and Nutrition Examination Survey (Centers for Disease Control and Prevention, National Center for Health Statistics) data at 20 years old.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
66 participants
Primary outcome timeframe
Followed to attainment of adult height, average of 11 years from date of randomization
Results posted on
2025-06-12
Participant Flow
66 participants were consented, two participants withdrew prior to randomization and two were compassionate exemption so were not randomized.
Participant milestones
| Measure |
Investigational Therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
31
|
|
Overall Study
Moved From Investigational to Standard Therapy
|
4
|
0
|
|
Overall Study
COMPLETED
|
21
|
24
|
|
Overall Study
NOT COMPLETED
|
10
|
7
|
Reasons for withdrawal
| Measure |
Investigational Therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
|
Overall Study
Physician Decision
|
1
|
1
|
|
Overall Study
Noncompliant
|
6
|
3
|
Baseline Characteristics
Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia
Baseline characteristics by cohort
| Measure |
Investigational Therapy
n=31 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=31 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
31 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
31 participants
n=5 Participants
|
31 participants
n=7 Participants
|
62 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Followed to attainment of adult height, average of 11 years from date of randomizationPopulation: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Adult height expressed in standard deviation score (SDS) units relative to the general population, with attainment of adult height defined as incremental growth \< 1.5 cm over 12 months. Adult height SDS was based on National Health and Nutrition Examination Survey (Centers for Disease Control and Prevention, National Center for Health Statistics) data at 20 years old.
Outcome measures
| Measure |
Investigational Therapy
n=18 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=27 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Adult Height Relative to General Population
|
-0.34 Standard Deviation Score (SDS) units
Standard Deviation 0.93
|
-0.6 Standard Deviation Score (SDS) units
Standard Deviation 0.89
|
SECONDARY outcome
Timeframe: Followed to attainment of adult height, average of 11 years from date of randomizationPopulation: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Adult height expressed in standard deviation score (SDS) units relative to the mid-parental height for the general population. Adult height is defined as incremental growth \< 1.5 cm over 12 months. Adult height SDS was based on National Health and Nutrition Examination Survey (Centers for Disease Control and Prevention, National Center for Health Statistics) data at 20 years old. Mid-parental height was calculated based on reported parental heights calculated as (father's height (cm) + mother's height (cm))/ 2 ± 6.5 (cm).
Outcome measures
| Measure |
Investigational Therapy
n=18 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=27 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Adult Height Relative to Mid-parental Height
Overall Participants
|
-0.45 Standard Deviation Score (SDS) units
Standard Deviation 0.85
|
-0.83 Standard Deviation Score (SDS) units
Standard Deviation 0.78
|
|
Adult Height Relative to Mid-parental Height
Males
|
-0.89 Standard Deviation Score (SDS) units
Standard Deviation 0.75
|
-0.93 Standard Deviation Score (SDS) units
Standard Deviation 0.78
|
|
Adult Height Relative to Mid-parental Height
Females
|
-0.02 Standard Deviation Score (SDS) units
Standard Deviation 0.72
|
-0.67 Standard Deviation Score (SDS) units
Standard Deviation 0.79
|
SECONDARY outcome
Timeframe: At date of randomization and at pubertal onset (average of seven years from date of randomization)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Predicted adult height was calculated using the bone age at the baseline visit or the first available bone age, using the Bayley-Pinneau method. Predicted adult height was calculated as the standard deviation score (SDS) units relative to the general population based on the National Health and Nutrition Examination Survey data (Centers for Disease Control and Prevention (CDC), National Center for Health Statistics) at 20 years old. Baseline was defined as time of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys).
Outcome measures
| Measure |
Investigational Therapy
n=25 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=33 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Predicted Adult Height
Baseline
|
-2.0 Standard Deviation Score (SDS) units
Standard Deviation 1.5
|
-2.1 Standard Deviation Score (SDS) units
Standard Deviation 1.5
|
|
Predicted Adult Height
Pubertal onset
|
-0.46 Standard Deviation Score (SDS) units
Standard Deviation 0.97
|
-0.98 Standard Deviation Score (SDS) units
Standard Deviation 1.01
|
SECONDARY outcome
Timeframe: From date of randomization to pubertal onset visit (which on average was seven years), pubertal onset to final visit (average was 4 years), and date of randomization to final visit (average of 11 years)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Changes in predicted adult height from baseline to pubertal onset, pubertal onset to final visit, and baseline to final visit. Adult height standard deviation score (SDS) was based on National Health and Nutrition Examination Survey (Centers for Disease Control and Prevention, National Center for Health Statistics) data at 20 years old. Predicted adult height at baseline was calculated using the bone age at the baseline visit or the first available bone age according to the Bayley-Pinneau method. Baseline was defined as date of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=17 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=26 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Predicted Adult Height Change
Baseline to pubertal onset visit
|
1.93 Standard Deviation Score (SDS) units
Standard Deviation 1.29
|
1.10 Standard Deviation Score (SDS) units
Standard Deviation 1.32
|
|
Predicted Adult Height Change
Pubertal onset to final visit
|
-0.10 Standard Deviation Score (SDS) units
Standard Deviation 0.66
|
0.14 Standard Deviation Score (SDS) units
Standard Deviation 0.54
|
|
Predicted Adult Height Change
Baseline to final visit
|
1.64 Standard Deviation Score (SDS) units
Standard Deviation 1.23
|
1.20 Standard Deviation Score (SDS) units
Standard Deviation 1.27
|
SECONDARY outcome
Timeframe: From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Number of prepubertal and pubertal years bone age remained unchanged. Baseline bone age was calculated using the bone age at the baseline visit or the first available bone age according to the Bayley-Pinneau method. Change in bone age from baseline to pubertal onset and pubertal onset to final visit was measured in years. Baseline was defined as date of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=18 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=27 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Number of Years Bone Age Remained Unchanged
Baseline to pubertal onset visit
|
3.86 Years
Standard Deviation 2.13
|
2.78 Years
Standard Deviation 2.43
|
|
Number of Years Bone Age Remained Unchanged
Pubertal onset to final visit
|
0.39 Years
Standard Deviation 0.68
|
0.70 Years
Standard Deviation 0.73
|
SECONDARY outcome
Timeframe: From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Changes in body mass index (BMI) were evaluated from baseline to puberty onset and puberty onset to final visit. BMI calculation was based on average of three early morning height measurements by stadiometer and weight measurement by scale for each timepoints. BMI was calculated as the standard deviation score (SDS) units relative to the general population based on the National Health and Nutrition Examination Survey data (Centers for Disease Control and Prevention (CDC), National Center for Health Statistics) at 20 years old. Baseline was defined as date of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was time at attainment of adult height, defined as incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=21 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=31 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Change in Body Mass Index (BMI)
Baseline to pubertal onset visit
|
0.12 Standard Deviation Score (SDS) units
Standard Deviation 0.7
|
0.36 Standard Deviation Score (SDS) units
Standard Deviation 0.79
|
|
Change in Body Mass Index (BMI)
Pubertal onset to final visit
|
-0.06 Standard Deviation Score (SDS) units
Standard Deviation 0.54
|
-0.20 Standard Deviation Score (SDS) units
Standard Deviation 0.61
|
SECONDARY outcome
Timeframe: Pubertal onset visit (average of seven years from date of randomization) and at final visit (average of 11 years from date of randomization)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Body mass index (BMI) was calculated based on average of three early morning height measurements by stadiometer and weight measurement by scale. BMI was calculated as the standard deviation score (SDS) units relative to the general population based on the National Health and Nutrition Examination Survey data (Centers for Disease Control and Prevention (CDC), National Center for Health Statistics) at 20 years old. Measures evaluated at pubertal onset and at final visit. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=21 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=31 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Body Mass Index (BMI)
Pubertal onset visit
|
1.07 Standard Deviation Score (SDS) units
Standard Deviation 1.30
|
1.09 Standard Deviation Score (SDS) units
Standard Deviation 0.93
|
|
Body Mass Index (BMI)
Final visit
|
0.79 Standard Deviation Score (SDS) units
Standard Deviation 1.13
|
0.89 Standard Deviation Score (SDS) units
Standard Deviation 0.83
|
SECONDARY outcome
Timeframe: From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Average annual growth (height) velocity, measured as the change in height over time relative to the population mean and adjusted for age and sex. Measured during the study period from baseline visit to pubertal onset visit (visits occurring approximately every 6 months) and from pubertal onset to adult height. Baseline was defined as date of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=21 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=31 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Average Annual Growth Velocity
Baseline to pubertal onset
|
-1.01 Standard Deviation Score (SDS) units
Standard Deviation 1.84
|
-0.34 Standard Deviation Score (SDS) units
Standard Deviation 2.18
|
|
Average Annual Growth Velocity
Pubertal onset to adult height
|
0.65 Standard Deviation Score (SDS) units
Standard Deviation 1.42
|
-0.29 Standard Deviation Score (SDS) units
Standard Deviation 1.34
|
SECONDARY outcome
Timeframe: At date of randomization, pubertal onset (average of seven years from date of randomization), and at final visit (average of 11 years from date of randomization)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Dose of oral hydrocortisone participant was taking adjusted for body surface area. Dose was recorded at baseline (first visit), pubertal onset, and at adult height (final visit). Baseline was defined as date of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=27 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=35 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Dose of Oral Hydrocortisone
Baseline
|
14.7 mg/m2 /day
Standard Deviation 3.8
|
13.9 mg/m2 /day
Standard Deviation 3.5
|
|
Dose of Oral Hydrocortisone
Pubertal onset
|
7.6 mg/m2 /day
Standard Deviation 1.5
|
15.0 mg/m2 /day
Standard Deviation 3.6
|
|
Dose of Oral Hydrocortisone
Adult height
|
16.4 mg/m2 /day
Standard Deviation 3.1
|
16.8 mg/m2 /day
Standard Deviation 2.9
|
SECONDARY outcome
Timeframe: From date of randomization to pubertal onset visit (which on average was seven years), pubertal onset to final visit (average was 4 years), and date of randomization to final visit (average of 11 years)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Average daily dose of oral hydrocortisone adjusted for body surface area. Dose was measured by developmental periods and for differences between sexes. Doses recorded at every visit, approximately every 6 months. Average dose measured from baseline to pubertal onset, from pubertal onset visit to adult height (final visit), and from baseline to adult height. Baseline was defined as date of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=21 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=31 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Average Daily Dose of Oral Hydrocortisone
Baseline to adult height
|
10.1 mg/m2 /day
Standard Deviation 1.7
|
15.0 mg/m2 /day
Standard Deviation 2.4
|
|
Average Daily Dose of Oral Hydrocortisone
Baseline to pubertal onset: Male
|
9.5 mg/m2 /day
Standard Deviation 1.6
|
15.0 mg/m2 /day
Standard Deviation 2.8
|
|
Average Daily Dose of Oral Hydrocortisone
Baseline to pubertal onset: Female
|
9.1 mg/m2 /day
Standard Deviation 1.5
|
13.9 mg/m2 /day
Standard Deviation 2.6
|
|
Average Daily Dose of Oral Hydrocortisone
Pubertal onset to adult height: Male
|
14.7 mg/m2 /day
Standard Deviation 0.9
|
15.5 mg/m2 /day
Standard Deviation 2.5
|
|
Average Daily Dose of Oral Hydrocortisone
Pubertal onset to adult height: Female
|
9.5 mg/m2 /day
Standard Deviation 2.2
|
15.5 mg/m2 /day
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Percentage of visits where early morning (pre-medication) 17-hydroxyprogesterone measurements fell within the optimal range (\<1,200 ng/dL) during the study period from baseline to pubertal onset and pubertal onset visit to final visit, with visits occurring approximately every 6 months. Baseline was defined as date of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=21 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=31 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Percent of Visits With 17-hydroxyprogesterone in the Optimal Range (<1,200 ng/dL)
Baseline to pubertal onset
|
11.8 Percentage of visits
Interval 5.9 to 22.7
|
35.9 Percentage of visits
Interval 19.4 to 65.2
|
|
Percent of Visits With 17-hydroxyprogesterone in the Optimal Range (<1,200 ng/dL)
Pubertal onset to adult height
|
0 Percentage of visits
Interval 0.0 to 30.0
|
28.6 Percentage of visits
Interval 11.8 to 54.5
|
SECONDARY outcome
Timeframe: From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Percentage of visits where early morning (pre-medication) androstenedione measurements fell within the normal range based on age and sex-specific ranges during the study period. Measurements done from baseline to pubertal onset visit, and from pubertal onset visit to adult height (final visit), with visits occurring approximately every 6 months. Baseline was defined as date of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=21 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=31 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Percent of Visits With Androstenedione in Normal Range
Baseline to pubertal onset
|
0 Percentage of visits
Interval 0.0 to 10.5
|
45 Percentage of visits
Interval 28.6 to 78.6
|
|
Percent of Visits With Androstenedione in Normal Range
Pubertal onset to final visit
|
20.2 Percentage of visits
Interval 0.0 to 50.0
|
50.0 Percentage of visits
Interval 25.0 to 81.8
|
SECONDARY outcome
Timeframe: From date of randomization to pubertal onset visit (which on average was seven years) and pubertal onset to final visit (average was 4 years)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Average testosterone based on early morning (pre-medication) testosterone levels measured for participants approximately every six months. Average testosterone measured from baseline to pubertal onset and from pubertal onset visit to adult height (final visit) by sex. Baseline was defined as date of randomization. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=21 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=31 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Average Testosterone
Baseline to pubertal onset
|
86.3 ng/dL
Interval 42.2 to 100.0
|
24.5 ng/dL
Interval 19.7 to 36.8
|
|
Average Testosterone
Pubertal onset to final visit: Males
|
336.0 ng/dL
Interval 303.3 to 492.5
|
418.4 ng/dL
Interval 349.6 to 504.4
|
|
Average Testosterone
Pubertal onset to final visit: Females
|
42.3 ng/dL
Interval 33.5 to 155.9
|
34.4 ng/dL
Interval 20.6 to 52.1
|
SECONDARY outcome
Timeframe: Measured from date of randomization to onset of early central pubertyPopulation: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Number of participants with onset of early central puberty, defined as testicular volume ≥ 4 mL in males before age 10, and breast Tanner stage 2 in females before age 9.
Outcome measures
| Measure |
Investigational Therapy
n=16 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=24 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Number of Participants With Onset of Early Central Puberty
|
12 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Followed from date of randomization to onset of menarchePopulation: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Average age at menarche (years) in female participants only.
Outcome measures
| Measure |
Investigational Therapy
n=9 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=11 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Average Age at Menarche
|
14.7 Years
Standard Deviation 1.7
|
13.6 Years
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: Measured at single time point at final visit, average of 11 years from date of randomizationPopulation: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Number of female participants with normal menstrual cyclicity at final visit. Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=8 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=10 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Number of Female Participants With Normal Menstrual Cyclicity at Final Visit
|
4 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Final visit, average of 11 years from date of randomizationPopulation: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Number of participants with Insulin resistance based on Homeostasis model assessment of insulin resistance (HOMA-IR) \> 2.5 at the final visit. Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=18 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=26 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Number of Participants With Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) > 2.5
|
8 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Measured at single time point at final visit, average of 11 years from date of randomizationPopulation: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Homeostasis model assessment of insulin resistance (HOMA-IR), a measure of insulin resistance, measured as insulin (μU/mL) × glucose (mmol/L)/22.5 at final visit. HOMA-IR value ≤ 2.5 is considered normal. HOMA-RI value \> 2.5 is considered abnormal. Higher HOMA-IR value indicates greater insulin resistance. Final visit was attainment of adult, defined as height with incremental growth \<1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=18 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=26 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Average (Median) Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
|
2.42 Units on a scale
Interval 2.12 to 4.82
|
2.29 Units on a scale
Interval 1.68 to 3.2
|
SECONDARY outcome
Timeframe: Pubertal onset visit (average of seven years from date of randomization) and at final visit (average of 11 years from date of randomization)Population: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Number of male participants with testicular adrenal rest tumors (TART), measured by scrotal ultrasound, at pubertal onset visit and final visit. Pubertal onset was defined as when patients entered puberty (Tanner 2 breast in females, testicle size ≥ 4 mL in males) or completed therapy with either aromatase inhibitor and/or GnRHa (age 13 years in girls and 14 years in boys). Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=12 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=20 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Number of Male Participants With Testicular Adrenal Rest Tumors (TART)
Pubertal onset
|
4 Participants
|
3 Participants
|
|
Number of Male Participants With Testicular Adrenal Rest Tumors (TART)
Final visit
|
7 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Final visit, average of 11 years from date of randomizationPopulation: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Anterior posterior spine bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DEXA) scan at final visit. The instrument specific comparisons (in standard deviations) were made to the average peak bone mass of a normal population, i.e. to the average bone mass of persons of the same age and sex as the patient. Final visit is defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=18 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=27 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Anterior Posterior Spine Bone Mineral Density (BMD) at Final Visit
|
-0.19 Z Scores
Standard Deviation 1.28
|
-0.25 Z Scores
Standard Deviation 0.84
|
SECONDARY outcome
Timeframe: Final visit, average of 11 years from date of randomizationPopulation: Modified intention-to-treat population, includes patients who were reassigned from investigational to standard therapy due to drug intolerance.
Femoral neck bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DEXA) scan at final visit. The instrument specific comparisons (in standard deviations) were made to the average peak bone mass of a normal population, i.e. to the average bone mass of persons of the same age and sex as the patient. Final visit was defined as attainment of adult height with incremental growth \< 1.5 cm over 12 months.
Outcome measures
| Measure |
Investigational Therapy
n=18 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=27 Participants
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Femoral Neck Bone Mineral Density (BMD) at Final Visit
|
-0.07 Z Scores
Standard Deviation 1.23
|
-0.32 Z Scores
Standard Deviation 1.03
|
Adverse Events
Investigational Therapy
Serious events: 3 serious events
Other events: 31 other events
Deaths: 0 deaths
Standard Therapy
Serious events: 10 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Investigational Therapy
n=31 participants at risk
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=35 participants at risk
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Cardiac disorders
Supraventricular tachycardia
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Endocrine disorders
Hypoglycaemic seizure
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Appendicitis
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Hepatobiliary disorders
Cholecystitis
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Infections and infestations
Viral infection
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Investigations
Liver function test increased
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Generalised tonic-clonic seizure
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Hospitalisation
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
22.9%
8/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Seizure
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
Other adverse events
| Measure |
Investigational Therapy
n=31 participants at risk
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls were randomized to receive antiandrogen (flutamide 10mg/kg/day orally), aromatase inhibitor (testolactone - 20mg/ kg/day orally OR letrozole - 1.5mg/m\^2 body surface area orally), low-dose hydrocortisone (6-8 mg/m\^2/day orally), and fludrocortisone (100-200 mcg/day, depending on lab evaluation, orally). Participants received the four-drug regimen until the age of 13 in the girls and 14 in the boys and then were switched to standard therapy. Female participants on investigational drugs were continued on flutamide until attainment of final adult height or two years post menarche. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
Standard Therapy
n=35 participants at risk
Children with congenital adrenal hyperplasia (CAH) and bone ages of 2-13 years in boys and 2-11 years in girls received standard therapy/conventional treatment (with hydrocortisone and fludrocortisone). Participants received hydrocortisone approximately 10-15 mg/m\^2/day orally, not exceeding 25mg/m\^2/day, and fludrocortisone 100-200 mcg/day orally depending on lab evaluation. Participants who experienced early puberty received GnRH agonist therapy: depot leuprolide 7.5-15 mg/kg monthly intramuscularly or deslorelin 4 mcg/kg/day (adjusted based on weight and response) subcutaneously.
|
|---|---|---|
|
Endocrine disorders
Hypothyroidism
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Endocrine disorders
Thyroiditis
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Abdominal pain
|
19.4%
6/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Dyspepsia
|
9.7%
3/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Nausea
|
19.4%
6/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Vomiting
|
67.7%
21/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
51.4%
18/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Injury, poisoning and procedural complications
Animal bite
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Investigations
Liver function test increased
|
19.4%
6/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
45.2%
14/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
28.6%
10/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Headache
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Petit mal epilepsy
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Somnambulism
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Syncope
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Psychiatric disorders
Panic attack
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Renal and urinary disorders
Nephrocalcinosis
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Renal and urinary disorders
Urinary tract infection
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Apnoea
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
9.7%
3/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Skin and subcutaneous tissue disorders
Laceration
|
6.5%
2/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
12.9%
4/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Social circumstances
Child abuse
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Limb reconstructive surgery
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Suture insertion
|
6.5%
2/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
11.4%
4/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Tonsillectomy
|
6.5%
2/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Blood and lymphatic system disorders
Lymphadenitis
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Diarrhoea
|
6.5%
2/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Gastroenteritis viral
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Lip injury
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Mumps
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
General disorders
Asthenia
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
General disorders
Fatigue
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Ear and labyrinth disorders
Ear infection
|
35.5%
11/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
17.1%
6/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Infections and infestations
Epstein-Barr virus infection
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Infections and infestations
External ear inflammation
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Infections and infestations
Febrile infection
|
96.8%
30/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
82.9%
29/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Infections and infestations
Mononucleosis syndrome
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Infections and infestations
Staphylococcal infection
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Infections and infestations
Streptococcal infection
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Injury, poisoning and procedural complications
Accident
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Injury, poisoning and procedural complications
Animal scratch
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Injury, poisoning and procedural complications
Burns first degree
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Injury, poisoning and procedural complications
Concussion
|
9.7%
3/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Injury, poisoning and procedural complications
Genital injury
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Investigations
Blood glucose decreased
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Investigations
Blood sodium decreased
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Musculoskeletal and connective tissue disorders
Multiple fractures
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal injury
|
9.7%
3/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
8.6%
3/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Anaesthesia
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Dizziness
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Lethargy
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Migraine
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Nervous system disorders
Seizure
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Renal and urinary disorders
Cystitis
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Renal and urinary disorders
Kidney infection
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Renal and urinary disorders
Lower urinary tract symptoms
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
6.5%
2/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
5.7%
2/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
6.5%
2/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Influenza
|
9.7%
3/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
14.3%
5/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Nasal injury
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis streptococcal
|
19.4%
6/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
37.1%
13/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Sinusitis
|
16.1%
5/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
14.3%
5/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Respiratory, thoracic and mediastinal disorders
Viral upper respiratory tract infection
|
6.5%
2/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
8.6%
3/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Skin and subcutaneous tissue disorders
Nail avulsion
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Skin and subcutaneous tissue disorders
Sunburn
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Skin and subcutaneous tissue disorders
Varicella
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Bladder training
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Dental care
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Dental operation
|
6.5%
2/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Emergency care
|
25.8%
8/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
28.6%
10/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Female genital operation
|
0.00%
0/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
2.9%
1/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Ligament operation
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Surgery
|
3.2%
1/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
0.00%
0/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
|
Surgical and medical procedures
Tooth extraction
|
12.9%
4/31 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
11.4%
4/35 • Up to 16 years from start of study
Reporting for standard therapy included four participants who transition from Investigational to Standard Therapy due to drug intolerance
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place