Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Duchenne and Becker Muscular Dystrophy, Muscular Dystrophy
Brief summary
This Phase II study is an open-label, multiple dose study to evaluate the safety, tolerability, PK, PD, clinical efficacy, behavior and neuropsychology, and physical functioning vamorolone over a treatment period of 12 weeks in steroid-naïve boys ages 2 to \<4 years, and glucocorticoid-treated and currently untreated boys ages 7 to \<18 years with DMD.
Detailed description
This Phase II study is an open-label, multiple dose study to evaluate the safety, tolerability, PK, PD, clinical efficacy, behavior and neuropsychology, and physical functioning of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg over a treatment period of 3 months in steroid-naïve boys ages 2 to \<4, and glucocorticoid-treated and currently untreated boys ages 7 to \<18 years with DMD. The study is comprised of a 5-week Pretreatment Screening Period; a 1-day Pretreatment Baseline Period; a 3-month open-label Treatment Period (Weeks 1-12); and a 4-8 week open-label Dose-tapering Period (starting from Weeks 13) for subjects who will not transition directly to further vamorolone or standard of care (SoC) glucocorticoid treatment at the end of the study. Subjects will be enrolled into the study at the Screening Visit, at the time written informed consent is obtained. Within the 2 to \<4 years age group, the initial 10 eligible subjects will be assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit. The subsequent 10 eligible subjects will be assigned to the 6.0 mg/kg/day treatment group at the Baseline Day -1 Visit. Within the 7 to \<18 years age group, both corticosteroid-treated and untreated, the initial 12 eligible subjects will be assigned to the 2.0 mg/kg/day treatment group at the Baseline Day -1 Visit. The subsequent 12 eligible subjects will be assigned to the 6.0 mg/kg/day treatment group at the Baseline Day -1 Visit. The first 6 subjects in each age group at 2 mg/kg will serve as the PK/safety run-in cohorts. PK assessments will be performed at week 2 and together with the safety assessment during the first 4 weeks of treatment this will be the basis to confirm whether 2 and 6 mg/kg/day will be used in the subsequent patients or if a dose adjustment is needed to avoid over or under-exposure in patients for any of the two age groups. Glucocorticoid-treated subjects in the 7 to \<18 years age group will take their final dose of SoC glucocorticoid therapy for DMD on Baseline Day -1, within 24 hours prior to administration of the first dose of vamorolone study medication. All subjects in both age groups will begin their assigned vamorolone treatment on Treatment Period Day 1, and will continue to receive their assigned vamorolone treatment throughout the duration of the 3 month Treatment Period (Weeks 1-12). At the end of the 3-month Treatment Period (Week 12), subjects will be given the option to receive vamorolone in an expanded access or compassionate use program, if possible, or to transition to SoC treatment for DMD (may include glucocorticoids). Subjects completing VBP15-006 and enrolling directly into the expanded access or compassionate use program or transitioning directly to SoC glucocorticoid treatment will not need to taper their vamorolone dose prior to participation in the expanded access or compassionate use program or initiation of SoC glucocorticoid treatment. All subjects who will not transition directly to further vamorolone or SoC glucocorticoid treatment will begin a 4 -8 week open label Dose tapering Period during which the dose of study medication will be progressively reduced and discontinued.
Interventions
DRUGVamorolone
Oral administration of vamorolone for 12 weeks.
Sponsors
Santhera Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Subject's parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to local requirements; 2. Subject has a centrally confirmed (by TRiNDS central genetic counselor\[s\]) diagnosis of DMD, defined as: 1. Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR 2. Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame,' and clinical picture consistent with typical DMD, OR 3. Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e., nonsense mutation, deletion/duplication leading to a downstream stop codon), with a clinical picture consistent with typical DMD; 3. Subject is male, 2 to \<4 years or 7 to \<18 years of age at time of enrollment in the study; 4. If 7 to \<18 years of age and currently taking standard of care glucocorticoids for treatment of DMD, subject has been taking standard of care glucocorticoids at stable dose for at least 3 months prior to enrollment in the study, and will continue the same stable dose regimen through the date of the Baseline Day -1 Visit. \[Note: Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to enrollment or if administered at stable dose beginning at least 4 weeks prior to enrollment and anticipated to be used at the stable dose regimen for the duration of the study\]; 5. If 7 to \<18 years of age, and not currently glucocorticoid-treated, subject has not received oral glucocorticoids or other oral immunosuppressive agents for at least 3 months prior to enrollment. \[Note: Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to enrollment or if administered at stable dose beginning at least 4 weeks prior to enrollment and anticipated to be used at the stable dose regimen for the duration of the study\]; 6. Clinical laboratory test results are within the normal range at the Screening Visit, or if abnormal, are not clinically significant, in the opinion of the Investigator. \[Notes: Serum gamma glutamyl transferase (GGT), creatinine, and total bilirubin all must be ≤ upper limit of the normal range at the Screening Visit. An abnormal vitamin D level that is considered clinically significant will not exclude a subject from participating\]; 7. Subject has evidence of chicken pox immunity as determined by: * Presence of IgG antibodies to varicella, as documented by a positive test result from the local laboratory from blood collected during the Screening Period; OR * Documentation, provided at the Screening Visit, that the subject has had 2 doses of varicella vaccine, with or without serologic evidence of immunity; the second of the 2 immunizations must have been given at least 14 days prior to assignment to a dose group; 8. Subject and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.
Exclusion criteria
1. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression; 2. Subject has current or history of chronic systemic fungal or viral infections; 3. Subject has used mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), or mexrenone (mexrenoate potassium) within 4 weeks prior to enrollment; 4. Subject has a history of primary hyperaldosteronism; 5. Subject has evidence of symptomatic cardiomyopathy \[Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary\]; 6. If 2 to \<4 years of age, subject is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents \[Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 1 month cumulative, with last use at least 3 months prior to enrollment, will be considered for eligibility on a case-by-case basis, unless discontinued for intolerance. Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to enrollment or if administered at stable dose beginning at least 4 weeks prior to enrollment and anticipated to be used at the stable dose regimen for the duration of the study\]; 7. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents; 8. Subject has used idebenone within 4 weeks prior to enrollment; 9. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator; 10. Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator; 11. Subject is taking (or has taken within 4 weeks prior to enrollment) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc); 12. Subject is taking (or has taken within 3 months prior to enrollment) any medication indicated for DMD, including Exondys51, Exondys53, Exondys45, Viltepso and Translarna; 13. Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication; 14. Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to enrollment; 15. Subject has previously been enrolled in the VBP15-006 study or any other vamorolone study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Eyes With Glaucoma | Baseline - Week 12 | Glaucoma was diagnosed by ocular pressure at Baseline and Week 12. |
| Change in Height (Z-score) From Baseline to Week 12 | Baseline, 12 weeks | Standing height will be assessed for subjects ages 2-\<4 years; height calculated from ulnar length in subjects ages 7-\<18. The z-score (standard score) is the number of standard deviations by which the outcome measure is above or below the value in the general population. A Z-score of 0 represents the population mean. A measure above the normal value has a positive z-score (higher height). |
| Change in Weight (Absolute) From Baseline to Week 12 | Baseline, 12 weeks | Body weight will be assessed at each of the scheduled time points. |
| Change in Weight (Percentile) From Baseline to Week 12 | Baseline, 12 weeks | Body weight will be assessed at each of the scheduled time points. |
| Change in Weight (Z-score) From Baseline to Week 12 | Baseline, 12 weeks | Body weight will be assessed at each of the scheduled time points. The z-score (standard score) is the number of standard deviations by which the outcome measure is above or below the value in the general population. A Z-score of 0 represents the population mean. A measure above the normal value has a positive z-score (higher weight). |
| Change in Body Mass Index (BMI) (Absolute) From Baseline to Week 12 | Baseline, Week 12 | Body Mass Index is a measure of weight adjusted for height. |
| Change in Body Mass Index (BMI) (Percentile) From Baseline to Week 12 | Baseline, Week 12 | Body Mass Index is a measure of weight adjusted for height. |
| Change in Body Mass Index (BMI) (Z-score) From Baseline to Week 12 | Baseline, Week 12 | Body Mass Index is a measure of weight adjusted for height. The z-score (standard score) is the number of standard deviations by which the outcome measure is above or below the value in the general population. A Z-score of 0 represents the population mean. A measure above the normal value has a positive z-score (higher BMI). |
| Change in Diastolic Blood Pressure | Day 1, Week 2, Week 6, Week 12, Week 16 | Change from Baseline to Week 12 in diastolic sitting blood pressure. |
| Change in Systolic Blood Pressure | Day 1, Week 2, Week 6, Week 12, Week 16 | Change from Baseline to Week 12 in systolic sitting blood pressure. |
| Number of Participants With Treatment Emergent Cushingoid Features | Baseline through Week 16 | Treatment emergent cushingoid features based on physical examination at all baseline, on-treatment and post-treatment assessments |
| Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Day 1, Week 6, Week 12, Week 16 | Each subject had blood drawn and urine collected for the standard hematology, chemistry and lipids clinical laboratory tests. In addition, fasting glucose and insulin, morning cortisol, as well as, in the additional 12 to \<18 years age group, LH, FSH, TSH, FT4 were collected. HbA1c determination had also to be performed if urine glucose was positive and/or fasted glucose levels was above normal limits. Any treatment-emergent clinically significant abnormal laboratory test result was reporte |
| Categorical Analysis of QTcF at Week 12 | Baseline, Week 12 | 12-lead 1electrocardiogram (ECG) as recorded after subject has rested quietly in a supine position for at least 5 minutes. ECG components are QRS duration, PR \[PQ\] interval, RR interval, QT interval and QTc. |
| Number of Eyes With Cataract | Baseline - Week 12 | Cataract was diagnosed by the presence of partial or complete opacity of the crystalline lens at Baseline and Week 12. |
| Number of Participants With Any Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed | An Adverse Event is any untoward medical occurrence in a subject and does not necessarily have to have a causal relationship with the intervention. Pre-existing conditions that worsen during the study are to be reported as AEs. |
| Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed | Drug related Adverse Events are TEAEs whose Causality were labeled as 'DEFINITE', 'POSSIBLE' or 'PROBABLE |
| Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed | Severe or medically significant but not immediately life -threatening: hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; incapacitating with inability to work or perform normal daily activity. |
| Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed (SAEs through 30 days after final dose of study drug) | A Serious Adverse Event (SAE) is defined as any AE regardless of causality that meets any of the following criteria: * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of an existing hospitalization * Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions * Results in a congenital anomaly/birth defect * Is an important medical event that may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above |
| Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Leading to Study Treatment Discontinuation | From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed | Adverse Events leading to Study treatment discontinuation |
| Change in Height (Absolute) From Baseline to Week 12 | Baseline, 12 weeks | Standing height will be assessed for subjects ages 2-\<4 years; height calculated from ulnar length in subjects ages 7-\<18. |
| Change in Height (Percentile) From Baseline to Week 12 | Baseline, 12 weeks | Standing height will be assessed for subjects ages 2-\<4 years; height calculated from ulnar length in subjects ages 7-\<18. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Descriptive Statistics of PK Parameters - Tmax | Day 1, Week 2 | Tmax is the time to reach the maximum observed concentration collected during a dosing interval |
| Descriptive Statistics of PK Parameters - Cmax | Day 1, Week 2 | Cmax is the maximum observed concentration |
| Descriptive Statistics of PK Parameters in Subjects Aged 2 to 4 Years - AUC 0-6 | Day 1, Week 2 | AUC 0-6 is the area under the concentration-time curve during the first 6 hours after dosing |
| Descriptive Statistics of PK Parameters in Subjects Aged 7 to 18 Years - AUC 0-inf | Day 1, Week 2 | AUC 0-8 is the area under the concentration-time curve after dosing extrapolated to infinity |
| Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1, Week 2 | The plasma concentration of vamorolone was measured on Day 1 and Week 2 predose, and 1h, 2h and 6h postdose and also 4h and 8h post in the 7-18 year groups. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Hemoglobin A1c [HbA1c]) | Baseline, Week 12 | Glucose, HbA1c and insulin were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication. The Baseline sample for HbA1c measurement may have been collected non-fasting. |
| Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Insulin) | Baseline, Week 12 | Glucose, HbA1c and insulin were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication. |
| Change From Baseline to Week 12 in Morning Cortisol Concentration | Baseline, Week 12 | Morning cortisol \[adrenal suppression\] samples were collected after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication at Day 1 and Week 12 Visits, before 10 AM local time |
| Change From Baseline to Week 12 in Bayley-III Gross Motor Scale (Ages 2 to <4 Years Only) | Baseline, Week 12 | The Bayley-III Gross Motor scale is a functional assessment, an accurate reflection of muscle strength for subjects with DMD ages 2 to \<4 years. The minimum score value is 0 and the maximum score value is 72. Higher scores mean a better outcome. |
| Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Type 1 Collagen C-telopeptide [CTX1]) | Baseline, Week 12 | Samples for CTX1, osteocalcin and P1NP were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication |
| Change From Baseline to Week 12 in Bone Turnover Biomarkers (Osteocalcin) | Baseline, Week 12 | Samples for CTX1, osteocalcin and P1NP were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication |
| Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Aminoterminal Propeptide of Type I Collagen [P1NP] ) | Baseline, Week 12 | Samples for CTX1, osteocalcin and P1NP were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication |
| Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Glucose) | Baseline, Week 12 | Glucose, HbA1c and insulin were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group 1 Patients in Treatment Group 1 must be ages 2-\<4 years and will receive Vamorolone at 2.0 mg/kg/day for the duration of the study. Treatment Group 1 will be enrolled prior to Treatment Group 2.
Vamorolone: Oral administration of vamorolone for 12 weeks. | 10 |
| Treatment Group 2 Patients in Treatment Group 2 must be ages 2-\<4 years and will receive Vamorolone at 6.0 mg/kg/day for the duration of the study. Treatment Group 2 will be enrolled after Treatment Group 1.
Vamorolone: Oral administration of vamorolone for 12 weeks. | 10 |
| Treatment Group 3 Patients in Treatment Group 3 must be ages 7-\<18 years and must be steroid untreated at entry. Treatment Group 3 will receive Vamorolone at 2.0 mg/kg/day for the duration of the study.
Vamorolone: Oral administration of vamorolone for 12 weeks. | 6 |
| Treatment Group 4 Patients in Treatment Group 4 must be ages 7-\<18 years and must be steroid untreated at entry. Treatment Group 4 will receive Vamorolone at 6.0 mg/kg/day for the duration of the study.
Vamorolone: Oral administration of vamorolone for 12 weeks. | 6 |
| Treatment Group 5 Patients in Treatment Group 5 must be ages 7-\<18 years and must be on a stable dose of steroid for 3 months prior to entry. Treatment Group 5 will receive Vamorolone at 2.0 mg/kg/day for the duration of the study.
Vamorolone: Oral administration of vamorolone for 12 weeks. | 6 |
| Treatment Group 6 Patients in Treatment Group 6 must be ages 7-\<18 years and must be on a stable dose of steroid for 3 months prior to entry. Treatment Group 6 will receive Vamorolone at 6.0 mg/kg/day for the duration of the study.
Vamorolone: Oral administration of vamorolone for 12 weeks. | 16 |
| Total | 54 |
Baseline characteristics
| Characteristic | Total | Treatment Group 6 | Treatment Group 5 | Treatment Group 4 | Treatment Group 3 | Treatment Group 2 | Treatment Group 1 |
|---|---|---|---|---|---|---|---|
| Age at first symptom | 31.7 months STANDARD_DEVIATION 21.88 | 42.8 months STANDARD_DEVIATION 27.59 | 32.2 months STANDARD_DEVIATION 14.26 | 51.0 months STANDARD_DEVIATION 23.92 | 30.0 months STANDARD_DEVIATION 15.18 | 14.2 months STANDARD_DEVIATION 4.47 | 20.8 months STANDARD_DEVIATION 5.67 |
| Age, Categorical <=18 years | 54 Participants | 16 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 10 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 14 Participants | 4 Participants | 3 Participants | 6 Participants | 10 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 37 Participants | 13 Participants | 3 Participants | 3 Participants | 5 Participants | 8 Participants | 5 Participants |
| Region of Enrollment Canada | 54 participants | 16 participants | 6 participants | 6 participants | 6 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 54 Participants | 16 Participants | 6 Participants | 6 Participants | 6 Participants | 10 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 16 |
| other Total, other adverse events | 7 / 10 | 9 / 10 | 6 / 6 | 4 / 6 | 3 / 6 | 11 / 16 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 6 | 1 / 6 | 0 / 6 | 1 / 16 |
Outcome results
Primary
Categorical Analysis of QTcF at Week 12
12-lead 1electrocardiogram (ECG) as recorded after subject has rested quietly in a supine position for at least 5 minutes. ECG components are QRS duration, PR \[PQ\] interval, RR interval, QT interval and QTc.
Time frame: Baseline, Week 12
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Group 1 | Categorical Analysis of QTcF at Week 12 | =< 450 msec | 10 Participants |
| Treatment Group 1 | Categorical Analysis of QTcF at Week 12 | > 450 msec | 0 Participants |
| Treatment Group 2 | Categorical Analysis of QTcF at Week 12 | =< 450 msec | 10 Participants |
| Treatment Group 2 | Categorical Analysis of QTcF at Week 12 | > 450 msec | 0 Participants |
| Treatment Group 3 | Categorical Analysis of QTcF at Week 12 | =< 450 msec | 6 Participants |
| Treatment Group 3 | Categorical Analysis of QTcF at Week 12 | > 450 msec | 0 Participants |
| Treatment Group 4 | Categorical Analysis of QTcF at Week 12 | =< 450 msec | 6 Participants |
| Treatment Group 4 | Categorical Analysis of QTcF at Week 12 | > 450 msec | 0 Participants |
| Treatment Group 5 | Categorical Analysis of QTcF at Week 12 | =< 450 msec | 5 Participants |
| Treatment Group 5 | Categorical Analysis of QTcF at Week 12 | > 450 msec | 0 Participants |
| Treatment Group 6 | Categorical Analysis of QTcF at Week 12 | =< 450 msec | 15 Participants |
| Treatment Group 6 | Categorical Analysis of QTcF at Week 12 | > 450 msec | 0 Participants |
Primary
Change in Body Mass Index (BMI) (Absolute) From Baseline to Week 12
Body Mass Index is a measure of weight adjusted for height.
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Body Mass Index (BMI) (Absolute) From Baseline to Week 12 | -0.09 kg/m2 | Standard Deviation 0.933 |
| Treatment Group 2 | Change in Body Mass Index (BMI) (Absolute) From Baseline to Week 12 | -0.04 kg/m2 | Standard Deviation 0.665 |
| Treatment Group 3 | Change in Body Mass Index (BMI) (Absolute) From Baseline to Week 12 | 0.05 kg/m2 | Standard Deviation 1.394 |
| Treatment Group 4 | Change in Body Mass Index (BMI) (Absolute) From Baseline to Week 12 | 1.53 kg/m2 | Standard Deviation 1.385 |
| Treatment Group 5 | Change in Body Mass Index (BMI) (Absolute) From Baseline to Week 12 | 0.82 kg/m2 | Standard Deviation 0.784 |
| Treatment Group 6 | Change in Body Mass Index (BMI) (Absolute) From Baseline to Week 12 | 0.60 kg/m2 | Standard Deviation 1.471 |
Primary
Change in Body Mass Index (BMI) (Percentile) From Baseline to Week 12
Body Mass Index is a measure of weight adjusted for height.
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Body Mass Index (BMI) (Percentile) From Baseline to Week 12 | -2.85 percentile | Standard Deviation 24.623 |
| Treatment Group 2 | Change in Body Mass Index (BMI) (Percentile) From Baseline to Week 12 | -1.61 percentile | Standard Deviation 12.509 |
| Treatment Group 3 | Change in Body Mass Index (BMI) (Percentile) From Baseline to Week 12 | -3.00 percentile | Standard Deviation 15.781 |
| Treatment Group 4 | Change in Body Mass Index (BMI) (Percentile) From Baseline to Week 12 | 10.78 percentile | Standard Deviation 7.312 |
| Treatment Group 5 | Change in Body Mass Index (BMI) (Percentile) From Baseline to Week 12 | 6.22 percentile | Standard Deviation 6.849 |
| Treatment Group 6 | Change in Body Mass Index (BMI) (Percentile) From Baseline to Week 12 | 4.44 percentile | Standard Deviation 11.498 |
Primary
Change in Body Mass Index (BMI) (Z-score) From Baseline to Week 12
Body Mass Index is a measure of weight adjusted for height. The z-score (standard score) is the number of standard deviations by which the outcome measure is above or below the value in the general population. A Z-score of 0 represents the population mean. A measure above the normal value has a positive z-score (higher BMI).
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Body Mass Index (BMI) (Z-score) From Baseline to Week 12 | -0.05 Z-score (score on a scale) | Standard Deviation 0.764 |
| Treatment Group 2 | Change in Body Mass Index (BMI) (Z-score) From Baseline to Week 12 | -0.02 Z-score (score on a scale) | Standard Deviation 0.495 |
| Treatment Group 3 | Change in Body Mass Index (BMI) (Z-score) From Baseline to Week 12 | 0.27 Z-score (score on a scale) | Standard Deviation 0.771 |
| Treatment Group 4 | Change in Body Mass Index (BMI) (Z-score) From Baseline to Week 12 | 1.10 Z-score (score on a scale) | Standard Deviation 0.584 |
| Treatment Group 5 | Change in Body Mass Index (BMI) (Z-score) From Baseline to Week 12 | 0.29 Z-score (score on a scale) | Standard Deviation 0.317 |
| Treatment Group 6 | Change in Body Mass Index (BMI) (Z-score) From Baseline to Week 12 | 0.29 Z-score (score on a scale) | Standard Deviation 0.483 |
Primary
Change in Diastolic Blood Pressure
Change from Baseline to Week 12 in diastolic sitting blood pressure.
Time frame: Day 1, Week 2, Week 6, Week 12, Week 16
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Diastolic Blood Pressure | -0.44 mmHg | Standard Deviation 8.248 |
| Treatment Group 2 | Change in Diastolic Blood Pressure | 2.00 mmHg | Standard Deviation 8.179 |
| Treatment Group 3 | Change in Diastolic Blood Pressure | -3.17 mmHg | Standard Deviation 7.333 |
| Treatment Group 4 | Change in Diastolic Blood Pressure | 5.80 mmHg | Standard Deviation 6.979 |
| Treatment Group 5 | Change in Diastolic Blood Pressure | 1.50 mmHg | Standard Deviation 6.95 |
| Treatment Group 6 | Change in Diastolic Blood Pressure | -2.40 mmHg | Standard Deviation 11.915 |
Primary
Change in Height (Absolute) From Baseline to Week 12
Standing height will be assessed for subjects ages 2-\<4 years; height calculated from ulnar length in subjects ages 7-\<18.
Time frame: Baseline, 12 weeks
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Height (Absolute) From Baseline to Week 12 | 1.98 cm | Standard Deviation 1.146 |
| Treatment Group 2 | Change in Height (Absolute) From Baseline to Week 12 | 2.35 cm | Standard Deviation 0.568 |
| Treatment Group 3 | Change in Height (Absolute) From Baseline to Week 12 | 0.55 cm | Standard Deviation 0.557 |
| Treatment Group 4 | Change in Height (Absolute) From Baseline to Week 12 | 2.29 cm | Standard Deviation 1.609 |
| Treatment Group 5 | Change in Height (Absolute) From Baseline to Week 12 | 0.60 cm | Standard Deviation 0.594 |
| Treatment Group 6 | Change in Height (Absolute) From Baseline to Week 12 | 1.27 cm | Standard Deviation 1.313 |
Primary
Change in Height (Percentile) From Baseline to Week 12
Standing height will be assessed for subjects ages 2-\<4 years; height calculated from ulnar length in subjects ages 7-\<18.
Time frame: Baseline, 12 weeks
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Height (Percentile) From Baseline to Week 12 | 1.17 percentile | Standard Deviation 11.538 |
| Treatment Group 2 | Change in Height (Percentile) From Baseline to Week 12 | 2.09 percentile | Standard Deviation 5.634 |
| Treatment Group 3 | Change in Height (Percentile) From Baseline to Week 12 | -3.89 percentile | Standard Deviation 3.907 |
| Treatment Group 4 | Change in Height (Percentile) From Baseline to Week 12 | 2.02 percentile | Standard Deviation 8.338 |
| Treatment Group 5 | Change in Height (Percentile) From Baseline to Week 12 | -3.69 percentile | Standard Deviation 3.408 |
| Treatment Group 6 | Change in Height (Percentile) From Baseline to Week 12 | -0.30 percentile | Standard Deviation 1.39 |
Primary
Change in Height (Z-score) From Baseline to Week 12
Standing height will be assessed for subjects ages 2-\<4 years; height calculated from ulnar length in subjects ages 7-\<18. The z-score (standard score) is the number of standard deviations by which the outcome measure is above or below the value in the general population. A Z-score of 0 represents the population mean. A measure above the normal value has a positive z-score (higher height).
Time frame: Baseline, 12 weeks
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Height (Z-score) From Baseline to Week 12 | 0.04 Z-score (score on a scale) | Standard Deviation 0.361 |
| Treatment Group 2 | Change in Height (Z-score) From Baseline to Week 12 | 0.14 Z-score (score on a scale) | Standard Deviation 0.201 |
| Treatment Group 3 | Change in Height (Z-score) From Baseline to Week 12 | -0.12 Z-score (score on a scale) | Standard Deviation 0.111 |
| Treatment Group 4 | Change in Height (Z-score) From Baseline to Week 12 | 0.07 Z-score (score on a scale) | Standard Deviation 0.253 |
| Treatment Group 5 | Change in Height (Z-score) From Baseline to Week 12 | -0.13 Z-score (score on a scale) | Standard Deviation 0.159 |
| Treatment Group 6 | Change in Height (Z-score) From Baseline to Week 12 | 0.00 Z-score (score on a scale) | Standard Deviation 0.194 |
Primary
Change in Systolic Blood Pressure
Change from Baseline to Week 12 in systolic sitting blood pressure.
Time frame: Day 1, Week 2, Week 6, Week 12, Week 16
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Systolic Blood Pressure | -2.33 mmHg | Standard Deviation 12.923 |
| Treatment Group 2 | Change in Systolic Blood Pressure | -2.20 mmHg | Standard Deviation 11.233 |
| Treatment Group 3 | Change in Systolic Blood Pressure | -2.50 mmHg | Standard Deviation 6.504 |
| Treatment Group 4 | Change in Systolic Blood Pressure | 5.00 mmHg | Standard Deviation 13.266 |
| Treatment Group 5 | Change in Systolic Blood Pressure | 2.50 mmHg | Standard Deviation 5.958 |
| Treatment Group 6 | Change in Systolic Blood Pressure | 0.07 mmHg | Standard Deviation 11.591 |
Primary
Change in Weight (Absolute) From Baseline to Week 12
Body weight will be assessed at each of the scheduled time points.
Time frame: Baseline, 12 weeks
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Weight (Absolute) From Baseline to Week 12 | 0.43 kg | Standard Deviation 0.776 |
| Treatment Group 2 | Change in Weight (Absolute) From Baseline to Week 12 | 0.65 kg | Standard Deviation 0.911 |
| Treatment Group 3 | Change in Weight (Absolute) From Baseline to Week 12 | -0.18 kg | Standard Deviation 3.259 |
| Treatment Group 4 | Change in Weight (Absolute) From Baseline to Week 12 | 3.47 kg | Standard Deviation 3.133 |
| Treatment Group 5 | Change in Weight (Absolute) From Baseline to Week 12 | 1.53 kg | Standard Deviation 1.188 |
| Treatment Group 6 | Change in Weight (Absolute) From Baseline to Week 12 | 1.94 kg | Standard Deviation 2.598 |
Primary
Change in Weight (Percentile) From Baseline to Week 12
Body weight will be assessed at each of the scheduled time points.
Time frame: Baseline, 12 weeks
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Weight (Percentile) From Baseline to Week 12 | -1.44 percentile | Standard Deviation 12.835 |
| Treatment Group 2 | Change in Weight (Percentile) From Baseline to Week 12 | -1.97 percentile | Standard Deviation 12.504 |
| Treatment Group 3 | Change in Weight (Percentile) From Baseline to Week 12 | -4.00 percentile | Standard Deviation 11.672 |
| Treatment Group 4 | Change in Weight (Percentile) From Baseline to Week 12 | 15.20 percentile | Standard Deviation 2.083 |
| Treatment Group 5 | Change in Weight (Percentile) From Baseline to Week 12 | 2.12 percentile | Standard Deviation 4.235 |
| Treatment Group 6 | Change in Weight (Percentile) From Baseline to Week 12 | 4.22 percentile | Standard Deviation 8.566 |
Primary
Change in Weight (Z-score) From Baseline to Week 12
Body weight will be assessed at each of the scheduled time points. The z-score (standard score) is the number of standard deviations by which the outcome measure is above or below the value in the general population. A Z-score of 0 represents the population mean. A measure above the normal value has a positive z-score (higher weight).
Time frame: Baseline, 12 weeks
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change in Weight (Z-score) From Baseline to Week 12 | -0.01 Z-score (score on a scale) | Standard Deviation 0.406 |
| Treatment Group 2 | Change in Weight (Z-score) From Baseline to Week 12 | 0.05 Z-score (score on a scale) | Standard Deviation 0.43 |
| Treatment Group 3 | Change in Weight (Z-score) From Baseline to Week 12 | -0.03 Z-score (score on a scale) | Standard Deviation 0.438 |
| Treatment Group 4 | Change in Weight (Z-score) From Baseline to Week 12 | 0.55 Z-score (score on a scale) | Standard Deviation 0.159 |
| Treatment Group 5 | Change in Weight (Z-score) From Baseline to Week 12 | 0.11 Z-score (score on a scale) | Standard Deviation 0.147 |
| Treatment Group 6 | Change in Weight (Z-score) From Baseline to Week 12 | 0.22 Z-score (score on a scale) | Standard Deviation 0.353 |
Primary
Number of Eyes With Cataract
Cataract was diagnosed by the presence of partial or complete opacity of the crystalline lens at Baseline and Week 12.
Time frame: Baseline - Week 12
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group 1 | Number of Eyes With Cataract | No Cataract : Baseline | 18 eyes |
| Treatment Group 1 | Number of Eyes With Cataract | No Cataract : Week 12 | 18 eyes |
| Treatment Group 1 | Number of Eyes With Cataract | Cataract : Baseline | 0 eyes |
| Treatment Group 1 | Number of Eyes With Cataract | Cataract : Week 12 | 0 eyes |
| Treatment Group 2 | Number of Eyes With Cataract | Cataract : Baseline | 0 eyes |
| Treatment Group 2 | Number of Eyes With Cataract | No Cataract : Week 12 | 8 eyes |
| Treatment Group 2 | Number of Eyes With Cataract | No Cataract : Baseline | 19 eyes |
| Treatment Group 2 | Number of Eyes With Cataract | Cataract : Week 12 | 0 eyes |
| Treatment Group 3 | Number of Eyes With Cataract | Cataract : Week 12 | 0 eyes |
| Treatment Group 3 | Number of Eyes With Cataract | Cataract : Baseline | 0 eyes |
| Treatment Group 3 | Number of Eyes With Cataract | No Cataract : Week 12 | 12 eyes |
| Treatment Group 3 | Number of Eyes With Cataract | No Cataract : Baseline | 12 eyes |
| Treatment Group 4 | Number of Eyes With Cataract | No Cataract : Baseline | 12 eyes |
| Treatment Group 4 | Number of Eyes With Cataract | Cataract : Week 12 | 0 eyes |
| Treatment Group 4 | Number of Eyes With Cataract | No Cataract : Week 12 | 10 eyes |
| Treatment Group 4 | Number of Eyes With Cataract | Cataract : Baseline | 0 eyes |
| Treatment Group 5 | Number of Eyes With Cataract | Cataract : Baseline | 4 eyes |
| Treatment Group 5 | Number of Eyes With Cataract | Cataract : Week 12 | 2 eyes |
| Treatment Group 5 | Number of Eyes With Cataract | No Cataract : Week 12 | 8 eyes |
| Treatment Group 5 | Number of Eyes With Cataract | No Cataract : Baseline | 8 eyes |
| Treatment Group 6 | Number of Eyes With Cataract | No Cataract : Week 12 | 15 eyes |
| Treatment Group 6 | Number of Eyes With Cataract | Cataract : Baseline | 15 eyes |
| Treatment Group 6 | Number of Eyes With Cataract | Cataract : Week 12 | 13 eyes |
| Treatment Group 6 | Number of Eyes With Cataract | No Cataract : Baseline | 17 eyes |
Primary
Number of Eyes With Glaucoma
Glaucoma was diagnosed by ocular pressure at Baseline and Week 12.
Time frame: Baseline - Week 12
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Group 1 | Number of Eyes With Glaucoma | No Glaucoma: Baseline | 18 eyes |
| Treatment Group 1 | Number of Eyes With Glaucoma | No Glaucoma: Week 12 | 18 eyes |
| Treatment Group 1 | Number of Eyes With Glaucoma | Suspected Glaucoma: Baseline | 0 eyes |
| Treatment Group 1 | Number of Eyes With Glaucoma | Suspected Glaucoma: Week 12 | 0 eyes |
| Treatment Group 1 | Number of Eyes With Glaucoma | Glaucoma: Baseline | 0 eyes |
| Treatment Group 1 | Number of Eyes With Glaucoma | Glaucoma: Week 12 | 0 eyes |
| Treatment Group 2 | Number of Eyes With Glaucoma | No Glaucoma: Week 12 | 8 eyes |
| Treatment Group 2 | Number of Eyes With Glaucoma | Suspected Glaucoma: Week 12 | 0 eyes |
| Treatment Group 2 | Number of Eyes With Glaucoma | Glaucoma: Week 12 | 0 eyes |
| Treatment Group 2 | Number of Eyes With Glaucoma | No Glaucoma: Baseline | 19 eyes |
| Treatment Group 2 | Number of Eyes With Glaucoma | Suspected Glaucoma: Baseline | 0 eyes |
| Treatment Group 2 | Number of Eyes With Glaucoma | Glaucoma: Baseline | 0 eyes |
| Treatment Group 3 | Number of Eyes With Glaucoma | Glaucoma: Week 12 | 0 eyes |
| Treatment Group 3 | Number of Eyes With Glaucoma | Glaucoma: Baseline | 0 eyes |
| Treatment Group 3 | Number of Eyes With Glaucoma | Suspected Glaucoma: Week 12 | 0 eyes |
| Treatment Group 3 | Number of Eyes With Glaucoma | Suspected Glaucoma: Baseline | 0 eyes |
| Treatment Group 3 | Number of Eyes With Glaucoma | No Glaucoma: Baseline | 12 eyes |
| Treatment Group 3 | Number of Eyes With Glaucoma | No Glaucoma: Week 12 | 12 eyes |
| Treatment Group 4 | Number of Eyes With Glaucoma | Suspected Glaucoma: Week 12 | 0 eyes |
| Treatment Group 4 | Number of Eyes With Glaucoma | No Glaucoma: Week 12 | 10 eyes |
| Treatment Group 4 | Number of Eyes With Glaucoma | Suspected Glaucoma: Baseline | 0 eyes |
| Treatment Group 4 | Number of Eyes With Glaucoma | Glaucoma: Week 12 | 0 eyes |
| Treatment Group 4 | Number of Eyes With Glaucoma | Glaucoma: Baseline | 0 eyes |
| Treatment Group 4 | Number of Eyes With Glaucoma | No Glaucoma: Baseline | 12 eyes |
| Treatment Group 5 | Number of Eyes With Glaucoma | No Glaucoma: Baseline | 8 eyes |
| Treatment Group 5 | Number of Eyes With Glaucoma | Glaucoma: Baseline | 0 eyes |
| Treatment Group 5 | Number of Eyes With Glaucoma | No Glaucoma: Week 12 | 8 eyes |
| Treatment Group 5 | Number of Eyes With Glaucoma | Suspected Glaucoma: Baseline | 0 eyes |
| Treatment Group 5 | Number of Eyes With Glaucoma | Suspected Glaucoma: Week 12 | 0 eyes |
| Treatment Group 5 | Number of Eyes With Glaucoma | Glaucoma: Week 12 | 0 eyes |
| Treatment Group 6 | Number of Eyes With Glaucoma | Suspected Glaucoma: Week 12 | 0 eyes |
| Treatment Group 6 | Number of Eyes With Glaucoma | Suspected Glaucoma: Baseline | 2 eyes |
| Treatment Group 6 | Number of Eyes With Glaucoma | Glaucoma: Baseline | 0 eyes |
| Treatment Group 6 | Number of Eyes With Glaucoma | Glaucoma: Week 12 | 0 eyes |
| Treatment Group 6 | Number of Eyes With Glaucoma | No Glaucoma: Week 12 | 15 eyes |
| Treatment Group 6 | Number of Eyes With Glaucoma | No Glaucoma: Baseline | 17 eyes |
Primary
Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Leading to Study Treatment Discontinuation
Adverse Events leading to Study treatment discontinuation
Time frame: From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed
Population: Safety set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Leading to Study Treatment Discontinuation | 0 Participants |
| Treatment Group 2 | Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Leading to Study Treatment Discontinuation | 0 Participants |
| Treatment Group 3 | Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Leading to Study Treatment Discontinuation | 0 Participants |
| Treatment Group 4 | Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Leading to Study Treatment Discontinuation | 0 Participants |
| Treatment Group 5 | Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Leading to Study Treatment Discontinuation | 0 Participants |
| Treatment Group 6 | Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) Leading to Study Treatment Discontinuation | 0 Participants |
Primary
Number of Participants With Any Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)
An Adverse Event is any untoward medical occurrence in a subject and does not necessarily have to have a causal relationship with the intervention. Pre-existing conditions that worsen during the study are to be reported as AEs.
Time frame: From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed
Population: Safety set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | Number of Participants With Any Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 7 Participants |
| Treatment Group 2 | Number of Participants With Any Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 9 Participants |
| Treatment Group 3 | Number of Participants With Any Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 6 Participants |
| Treatment Group 4 | Number of Participants With Any Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 4 Participants |
| Treatment Group 5 | Number of Participants With Any Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 3 Participants |
| Treatment Group 6 | Number of Participants With Any Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 12 Participants |
Primary
Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result
Each subject had blood drawn and urine collected for the standard hematology, chemistry and lipids clinical laboratory tests. In addition, fasting glucose and insulin, morning cortisol, as well as, in the additional 12 to \<18 years age group, LH, FSH, TSH, FT4 were collected. HbA1c determination had also to be performed if urine glucose was positive and/or fasted glucose levels was above normal limits. Any treatment-emergent clinically significant abnormal laboratory test result was reporte
Time frame: Day 1, Week 6, Week 12, Week 16
Population: Safety set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Group 1 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood TSH increased | 0 Participants |
| Treatment Group 1 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood glucose decreased | 0 Participants |
| Treatment Group 1 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Cortisol decreased | 0 Participants |
| Treatment Group 1 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Tyroxin free increased | 0 Participants |
| Treatment Group 1 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood insulin increased | 0 Participants |
| Treatment Group 2 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood glucose decreased | 0 Participants |
| Treatment Group 2 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood TSH increased | 0 Participants |
| Treatment Group 2 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Cortisol decreased | 1 Participants |
| Treatment Group 2 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Tyroxin free increased | 0 Participants |
| Treatment Group 2 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood insulin increased | 0 Participants |
| Treatment Group 3 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood glucose decreased | 0 Participants |
| Treatment Group 3 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood TSH increased | 0 Participants |
| Treatment Group 3 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Tyroxin free increased | 0 Participants |
| Treatment Group 3 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood insulin increased | 0 Participants |
| Treatment Group 3 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Cortisol decreased | 2 Participants |
| Treatment Group 4 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood insulin increased | 0 Participants |
| Treatment Group 4 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Cortisol decreased | 0 Participants |
| Treatment Group 4 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood glucose decreased | 0 Participants |
| Treatment Group 4 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood TSH increased | 0 Participants |
| Treatment Group 4 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Tyroxin free increased | 0 Participants |
| Treatment Group 5 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood TSH increased | 0 Participants |
| Treatment Group 5 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Cortisol decreased | 0 Participants |
| Treatment Group 5 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Tyroxin free increased | 0 Participants |
| Treatment Group 5 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood glucose decreased | 0 Participants |
| Treatment Group 5 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood insulin increased | 0 Participants |
| Treatment Group 6 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Cortisol decreased | 2 Participants |
| Treatment Group 6 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood TSH increased | 1 Participants |
| Treatment Group 6 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood glucose decreased | 1 Participants |
| Treatment Group 6 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Tyroxin free increased | 1 Participants |
| Treatment Group 6 | Number of Participants With Clinically Significant Treatment-emergent Abnormal Clinical Laboratory Test Result | Blood insulin increased | 1 Participants |
Primary
Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)
Drug related Adverse Events are TEAEs whose Causality were labeled as 'DEFINITE', 'POSSIBLE' or 'PROBABLE
Time frame: From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed
Population: Safety set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 1 Participants |
| Treatment Group 2 | Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 7 Participants |
| Treatment Group 3 | Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 3 Participants |
| Treatment Group 4 | Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 4 Participants |
| Treatment Group 5 | Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 1 Participants |
| Treatment Group 6 | Number of Participants With Drug Related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 8 Participants |
Primary
Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)
A Serious Adverse Event (SAE) is defined as any AE regardless of causality that meets any of the following criteria: * Results in death * Is life-threatening * Requires inpatient hospitalization or prolongation of an existing hospitalization * Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions * Results in a congenital anomaly/birth defect * Is an important medical event that may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above
Time frame: From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed (SAEs through 30 days after final dose of study drug)
Population: Safety set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 0 Participants |
| Treatment Group 2 | Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 0 Participants |
| Treatment Group 3 | Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 0 Participants |
| Treatment Group 4 | Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 1 Participants |
| Treatment Group 5 | Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 0 Participants |
| Treatment Group 6 | Number of Participants With Serious Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 1 Participants |
Primary
Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03)
Severe or medically significant but not immediately life -threatening: hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; incapacitating with inability to work or perform normal daily activity.
Time frame: From the date of the subject's written informed consent until the final Week 16 Visit or the subject's participation in the study was completed
Population: Safety set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 0 Participants |
| Treatment Group 2 | Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 0 Participants |
| Treatment Group 3 | Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 0 Participants |
| Treatment Group 4 | Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 1 Participants |
| Treatment Group 5 | Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 0 Participants |
| Treatment Group 6 | Number of Participants With Severe Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE v4.03) | 1 Participants |
Primary
Number of Participants With Treatment Emergent Cushingoid Features
Treatment emergent cushingoid features based on physical examination at all baseline, on-treatment and post-treatment assessments
Time frame: Baseline through Week 16
Population: Safety set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | Number of Participants With Treatment Emergent Cushingoid Features | 0 Participants |
| Treatment Group 2 | Number of Participants With Treatment Emergent Cushingoid Features | 0 Participants |
| Treatment Group 3 | Number of Participants With Treatment Emergent Cushingoid Features | 0 Participants |
| Treatment Group 4 | Number of Participants With Treatment Emergent Cushingoid Features | 1 Participants |
| Treatment Group 5 | Number of Participants With Treatment Emergent Cushingoid Features | 0 Participants |
| Treatment Group 6 | Number of Participants With Treatment Emergent Cushingoid Features | 0 Participants |
Secondary
Descriptive Statistics of PK Parameters - Cmax
Cmax is the maximum observed concentration
Time frame: Day 1, Week 2
Population: PK analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group 1 | Descriptive Statistics of PK Parameters - Cmax | Day 1 | 246.8 ng/mL | Standard Deviation 2.01 |
| Treatment Group 1 | Descriptive Statistics of PK Parameters - Cmax | Week 2 | 349.3 ng/mL | Standard Deviation 2.06 |
| Treatment Group 2 | Descriptive Statistics of PK Parameters - Cmax | Week 2 | 719.5 ng/mL | Standard Deviation 2.23 |
| Treatment Group 2 | Descriptive Statistics of PK Parameters - Cmax | Day 1 | 781.7 ng/mL | Standard Deviation 1.77 |
| Treatment Group 3 | Descriptive Statistics of PK Parameters - Cmax | Day 1 | 254.5 ng/mL | Standard Deviation 2.04 |
| Treatment Group 3 | Descriptive Statistics of PK Parameters - Cmax | Week 2 | 334.5 ng/mL | Standard Deviation 1.67 |
| Treatment Group 4 | Descriptive Statistics of PK Parameters - Cmax | Day 1 | 922.2 ng/mL | Standard Deviation 1.6 |
| Treatment Group 4 | Descriptive Statistics of PK Parameters - Cmax | Week 2 | 765.5 ng/mL | Standard Deviation 1.59 |
Secondary
Descriptive Statistics of PK Parameters in Subjects Aged 2 to 4 Years - AUC 0-6
AUC 0-6 is the area under the concentration-time curve during the first 6 hours after dosing
Time frame: Day 1, Week 2
Population: PK analysis set - Subjects aged 2 to 4 years
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group 1 | Descriptive Statistics of PK Parameters in Subjects Aged 2 to 4 Years - AUC 0-6 | Day 1 | 816.3 ng.h/mL | Standard Deviation 1.72 |
| Treatment Group 1 | Descriptive Statistics of PK Parameters in Subjects Aged 2 to 4 Years - AUC 0-6 | Week 2 | 1448.4 ng.h/mL | Standard Deviation 1.38 |
| Treatment Group 2 | Descriptive Statistics of PK Parameters in Subjects Aged 2 to 4 Years - AUC 0-6 | Day 1 | 2216.2 ng.h/mL | Standard Deviation 1.47 |
| Treatment Group 2 | Descriptive Statistics of PK Parameters in Subjects Aged 2 to 4 Years - AUC 0-6 | Week 2 | 2571.6 ng.h/mL | Standard Deviation 2.02 |
Secondary
Descriptive Statistics of PK Parameters in Subjects Aged 7 to 18 Years - AUC 0-inf
AUC 0-8 is the area under the concentration-time curve after dosing extrapolated to infinity
Time frame: Day 1, Week 2
Population: PK analysis set - subjects aged 7 to 18 years
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group 1 | Descriptive Statistics of PK Parameters in Subjects Aged 7 to 18 Years - AUC 0-inf | Day 1 | 1253.0 ng.h/mL | Standard Deviation 1.65 |
| Treatment Group 1 | Descriptive Statistics of PK Parameters in Subjects Aged 7 to 18 Years - AUC 0-inf | Week 2 | 1528.6 ng.h/mL | Standard Deviation 1.15 |
| Treatment Group 2 | Descriptive Statistics of PK Parameters in Subjects Aged 7 to 18 Years - AUC 0-inf | Day 1 | 4119.8 ng.h/mL | Standard Deviation 1.53 |
| Treatment Group 2 | Descriptive Statistics of PK Parameters in Subjects Aged 7 to 18 Years - AUC 0-inf | Week 2 | 3587.7 ng.h/mL | Standard Deviation 1.72 |
Secondary
Descriptive Statistics of PK Parameters - Tmax
Tmax is the time to reach the maximum observed concentration collected during a dosing interval
Time frame: Day 1, Week 2
Population: PK analysis set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment Group 1 | Descriptive Statistics of PK Parameters - Tmax | Day 1 | 2.0 h |
| Treatment Group 1 | Descriptive Statistics of PK Parameters - Tmax | Week 2 | 1.9 h |
| Treatment Group 2 | Descriptive Statistics of PK Parameters - Tmax | Week 2 | 2.0 h |
| Treatment Group 2 | Descriptive Statistics of PK Parameters - Tmax | Day 1 | 2.0 h |
| Treatment Group 3 | Descriptive Statistics of PK Parameters - Tmax | Day 1 | 2.0 h |
| Treatment Group 3 | Descriptive Statistics of PK Parameters - Tmax | Week 2 | 2.9 h |
| Treatment Group 4 | Descriptive Statistics of PK Parameters - Tmax | Day 1 | 2.0 h |
| Treatment Group 4 | Descriptive Statistics of PK Parameters - Tmax | Week 2 | 2.0 h |
Secondary
Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2
The plasma concentration of vamorolone was measured on Day 1 and Week 2 predose, and 1h, 2h and 6h postdose and also 4h and 8h post in the 7-18 year groups.
Time frame: Day 1, Week 2
Population: PK analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group 1 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - predose | 0.0 ng / mL | Standard Deviation 0 |
| Treatment Group 1 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 6h | 125.7 ng / mL | Standard Deviation 84.83 |
| Treatment Group 1 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 6h | 134.5 ng / mL | Standard Deviation 110.99 |
| Treatment Group 1 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 1h | 198.3 ng / mL | Standard Deviation 196.67 |
| Treatment Group 1 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - predose | 0.0 ng / mL | Standard Deviation 0 |
| Treatment Group 1 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 2h | 360.4 ng / mL | Standard Deviation 222.93 |
| Treatment Group 1 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 1h | 346.0 ng / mL | Standard Deviation 329.08 |
| Treatment Group 1 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 2h | 236.7 ng / mL | Standard Deviation 153.58 |
| Treatment Group 2 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - predose | 0.0 ng / mL | Standard Deviation 0 |
| Treatment Group 2 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 6h | 280.0 ng / mL | Standard Deviation 249.99 |
| Treatment Group 2 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 6h | 272.0 ng / mL | Standard Deviation 109.71 |
| Treatment Group 2 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 2h | 769.3 ng / mL | Standard Deviation 527.67 |
| Treatment Group 2 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 1h | 409.8 ng / mL | Standard Deviation 385.65 |
| Treatment Group 2 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 2h | 829.4 ng / mL | Standard Deviation 740.83 |
| Treatment Group 2 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - predose | 0.0 ng / mL | Standard Deviation 0 |
| Treatment Group 2 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 1h | 471.3 ng / mL | Standard Deviation 333.61 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 1h | 142.5 ng / mL | Standard Deviation 225.74 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - predose | 0.0 ng / mL | Standard Deviation 0 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 2h | 216.4 ng / mL | Standard Deviation 181.19 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 4h | 163.8 ng / mL | Standard Deviation 103.74 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 6h | 148.0 ng / mL | Standard Deviation 109.33 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 8h | 78.5 ng / mL | Standard Deviation 41.66 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - predose | 0.7 ng / mL | Standard Deviation 2.06 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 1h | 192.0 ng / mL | Standard Deviation 199.92 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 2h | 217.8 ng / mL | Standard Deviation 149.31 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 4h | 207.6 ng / mL | Standard Deviation 167.99 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 6h | 158.9 ng / mL | Standard Deviation 105.34 |
| Treatment Group 3 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 8h | 55.8 ng / mL | Standard Deviation 31.81 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - predose | 0.0 ng / mL | Standard Deviation 0 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 1h | 463.7 ng / mL | Standard Deviation 348.19 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 8h | 170.6 ng / mL | Standard Deviation 183.67 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 2h | 780.5 ng / mL | Standard Deviation 457.91 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 1h | 519.1 ng / mL | Standard Deviation 437.26 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 6h | 389.1 ng / mL | Standard Deviation 307.57 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - predose | 2.9 ng / mL | Standard Deviation 5.22 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 2h | 686.3 ng / mL | Standard Deviation 369.69 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 4h | 711.1 ng / mL | Standard Deviation 353.6 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 6h | 300.2 ng / mL | Standard Deviation 206.18 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 8h | 174.7 ng / mL | Standard Deviation 137.78 |
| Treatment Group 4 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 4h | 603.0 ng / mL | Standard Deviation 346.88 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 2h | 216.4 ng / mL | Standard Deviation 181.19 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 8h | 78.5 ng / mL | Standard Deviation 41.66 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - predose | 0.0 ng / mL | Standard Deviation 0 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 4h | 163.8 ng / mL | Standard Deviation 103.74 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 1h | 142.5 ng / mL | Standard Deviation 225.74 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 8h | 55.8 ng / mL | Standard Deviation 31.81 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 6h | 148.0 ng / mL | Standard Deviation 109.33 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 4h | 207.6 ng / mL | Standard Deviation 167.99 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 1h | 192.0 ng / mL | Standard Deviation 199.92 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 6h | 158.9 ng / mL | Standard Deviation 105.34 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 2h | 217.8 ng / mL | Standard Deviation 149.31 |
| Treatment Group 5 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - predose | 0.7 ng / mL | Standard Deviation 2.06 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 6h | 389.1 ng / mL | Standard Deviation 307.57 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 8h | 170.6 ng / mL | Standard Deviation 183.67 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - predose | 2.9 ng / mL | Standard Deviation 5.22 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 1h | 519.1 ng / mL | Standard Deviation 437.26 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 6h | 300.2 ng / mL | Standard Deviation 206.18 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 1h | 463.7 ng / mL | Standard Deviation 348.19 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - predose | 0.0 ng / mL | Standard Deviation 0 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 8h | 174.7 ng / mL | Standard Deviation 137.78 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 2h | 686.3 ng / mL | Standard Deviation 369.69 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Week 2 - 4h | 603.0 ng / mL | Standard Deviation 346.88 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 4h | 711.1 ng / mL | Standard Deviation 353.6 |
| Treatment Group 6 | Pre-dose and Post-dose Plasma Concentration Measurements of Vamorolone at Day 1 and Week 2 | Day 1 - 2h | 780.5 ng / mL | Standard Deviation 457.91 |
Other Pre-specified
Change From Baseline to Week 12 in Bayley-III Gross Motor Scale (Ages 2 to <4 Years Only)
The Bayley-III Gross Motor scale is a functional assessment, an accurate reflection of muscle strength for subjects with DMD ages 2 to \<4 years. The minimum score value is 0 and the maximum score value is 72. Higher scores mean a better outcome.
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change From Baseline to Week 12 in Bayley-III Gross Motor Scale (Ages 2 to <4 Years Only) | 0.44 score on a scale | Standard Deviation 1.13 |
| Treatment Group 2 | Change From Baseline to Week 12 in Bayley-III Gross Motor Scale (Ages 2 to <4 Years Only) | 2.50 score on a scale | Standard Deviation 1.716 |
Other Pre-specified
Change From Baseline to Week 12 in Bone Turnover Biomarkers (Osteocalcin)
Samples for CTX1, osteocalcin and P1NP were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Osteocalcin) | -3.340 ug/L | Standard Deviation 21.055 |
| Treatment Group 2 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Osteocalcin) | 2.422 ug/L | Standard Deviation 10.696 |
| Treatment Group 3 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Osteocalcin) | 14.817 ug/L | Standard Deviation 18.7328 |
| Treatment Group 4 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Osteocalcin) | -1.120 ug/L | Standard Deviation 15.8528 |
| Treatment Group 5 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Osteocalcin) | 31.700 ug/L | Standard Deviation 11.6915 |
| Treatment Group 6 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Osteocalcin) | 16.546 ug/L | Standard Deviation 9.1486 |
Other Pre-specified
Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Aminoterminal Propeptide of Type I Collagen [P1NP] )
Samples for CTX1, osteocalcin and P1NP were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Aminoterminal Propeptide of Type I Collagen [P1NP] ) | -39.870 ug/L | Standard Deviation 188.7787 |
| Treatment Group 2 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Aminoterminal Propeptide of Type I Collagen [P1NP] ) | 14.478 ug/L | Standard Deviation 117.5704 |
| Treatment Group 3 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Aminoterminal Propeptide of Type I Collagen [P1NP] ) | 19.067 ug/L | Standard Deviation 78.6139 |
| Treatment Group 4 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Aminoterminal Propeptide of Type I Collagen [P1NP] ) | -82.840 ug/L | Standard Deviation 178.0726 |
| Treatment Group 5 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Aminoterminal Propeptide of Type I Collagen [P1NP] ) | 318.850 ug/L | Standard Deviation 99.0038 |
| Treatment Group 6 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Aminoterminal Propeptide of Type I Collagen [P1NP] ) | 149.671 ug/L | Standard Deviation 106.2874 |
Other Pre-specified
Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Type 1 Collagen C-telopeptide [CTX1])
Samples for CTX1, osteocalcin and P1NP were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Type 1 Collagen C-telopeptide [CTX1]) | 28.300 ng/L | Standard Deviation 387.1423 |
| Treatment Group 2 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Type 1 Collagen C-telopeptide [CTX1]) | 138.000 ng/L | Standard Deviation 257.664 |
| Treatment Group 3 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Type 1 Collagen C-telopeptide [CTX1]) | 93.500 ng/L | Standard Deviation 235.7446 |
| Treatment Group 4 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Type 1 Collagen C-telopeptide [CTX1]) | 101.800 ng/L | Standard Deviation 365.3542 |
| Treatment Group 5 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Type 1 Collagen C-telopeptide [CTX1]) | 631.833 ng/L | Standard Deviation 155.3621 |
| Treatment Group 6 | Change From Baseline to Week 12 in Bone Turnover Biomarkers (Serum Type 1 Collagen C-telopeptide [CTX1]) | 273.000 ng/L | Standard Deviation 335.4937 |
Other Pre-specified
Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Glucose)
Glucose, HbA1c and insulin were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication.
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Glucose) | -0.160 mmol/L | Standard Deviation 0.2912 |
| Treatment Group 2 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Glucose) | -0.243 mmol/L | Standard Deviation 0.6309 |
| Treatment Group 3 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Glucose) | -0.063 mmol/L | Standard Deviation 0.3524 |
| Treatment Group 4 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Glucose) | -0.335 mmol/L | Standard Deviation 0.3815 |
| Treatment Group 5 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Glucose) | 0.195 mmol/L | Standard Deviation 0.5727 |
| Treatment Group 6 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Glucose) | -0.254 mmol/L | Standard Deviation 0.3909 |
Other Pre-specified
Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Hemoglobin A1c [HbA1c])
Glucose, HbA1c and insulin were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication. The Baseline sample for HbA1c measurement may have been collected non-fasting.
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Hemoglobin A1c [HbA1c]) | 0.1 percent | Standard Deviation 0.26 |
| Treatment Group 2 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Hemoglobin A1c [HbA1c]) | 0.0 percent | Standard Deviation 0.15 |
| Treatment Group 3 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Hemoglobin A1c [HbA1c]) | 0.0 percent | Standard Deviation 0.16 |
| Treatment Group 4 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Hemoglobin A1c [HbA1c]) | 0.0 percent | Standard Deviation 0.1 |
| Treatment Group 5 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Hemoglobin A1c [HbA1c]) | 0.0 percent | Standard Deviation 0.11 |
| Treatment Group 6 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Hemoglobin A1c [HbA1c]) | -0.1 percent | Standard Deviation 0.12 |
Other Pre-specified
Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Insulin)
Glucose, HbA1c and insulin were collected at the Day 1 and Week 12 Visits after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication.
Time frame: Baseline, Week 12
Population: Safety set - No subjects were analyzed in Group 1 and 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Insulin) | 6.333 pmol/L | Standard Deviation 20.5183 |
| Treatment Group 2 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Insulin) | 0.667 pmol/L | Standard Deviation 33.0051 |
| Treatment Group 3 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Insulin) | 46.333 pmol/L | Standard Deviation 51.9256 |
| Treatment Group 4 | Change From Baseline to Week 12 in Insulin Resistance Biomarkers (Insulin) | -26.333 pmol/L | Standard Deviation 51.1493 |
Other Pre-specified
Change From Baseline to Week 12 in Morning Cortisol Concentration
Morning cortisol \[adrenal suppression\] samples were collected after the subject has fasted for ≥ 6 hours and prior to administration of the daily dose of study medication at Day 1 and Week 12 Visits, before 10 AM local time
Time frame: Baseline, Week 12
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group 1 | Change From Baseline to Week 12 in Morning Cortisol Concentration | -184.700 nmol/L | Standard Deviation 138.202 |
| Treatment Group 2 | Change From Baseline to Week 12 in Morning Cortisol Concentration | -217.750 nmol/L | Standard Deviation 103.9832 |
| Treatment Group 3 | Change From Baseline to Week 12 in Morning Cortisol Concentration | -110.667 nmol/L | Standard Deviation 85.8596 |
| Treatment Group 4 | Change From Baseline to Week 12 in Morning Cortisol Concentration | -248.667 nmol/L | Standard Deviation 186.906 |
| Treatment Group 5 | Change From Baseline to Week 12 in Morning Cortisol Concentration | 12.000 nmol/L | Standard Deviation 49.3356 |
| Treatment Group 6 | Change From Baseline to Week 12 in Morning Cortisol Concentration | -34.933 nmol/L | Standard Deviation 42.1485 |