Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne Muscular Dystrophy, vamorolone
Brief summary
The purpose of this study is to determine whether a new medication called vamorolone is safe and well-tolerated by boys with Duchenne muscular dystrophy (DMD) ages ≥ 4 and \< 7 years old.
Detailed description
This study will evaluate the safety and tolerability of a new steroid-like medication called vamorolone in boys with DMD ages ≥ 4 years and \< 7 years. Enrolled participants will take the study medication for 14 days followed by a 14 day follow-up period. The potential effectiveness of vamorolone in treating DMD will also be explored.
Interventions
DRUGVamorolone 0.25 mg/kg/day
Oral administration of 0.25 mg/kg/day daily for 14 days.
DRUGVamorolone 0.75 mg/kg/day
Oral administration of 0.75 mg/kg/day daily for 14 days.
DRUGVamorolone 2.0 mg/kg/day
Oral administration of 2.0 mg/kg/day daily for 14 days.
DRUGVamorolone 6.0 mg/kg/day
Oral administration of 6 mg/kg/day daily for 14 days.
Sponsors
University of Pittsburgh
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Neurological Disorders and Stroke (NINDS)
Cooperative International Neuromuscular Research Group
ReveraGen BioPharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
4 Years to 6 Years
Healthy volunteers
No
Inclusion criteria
1. Subject's parent or legal guardian has provided written informed consent/Health Insurance Portability and Accountability Act (HIPAA) authorization prior to any study-related procedures; 2. Subject has a confirmed (by Central Genetic Counselor) diagnosis of DMD as 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 typical clinical picture of DMD; 3. Subject is ≥ 4 years and \< 7 years of age at time of enrollment in the study; 4. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance, as assessed at the Screening and Baseline Visits; 5. 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. (Note: Serum gamma glutamyl transferase \[GGT\], creatinine, and total bilirubin all must be ≤ upper limit of the normal range at the Screening Visit); 6. 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 testing laboratory at the Screening Visit; and 7. Subject and parent/guardian 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 had an acute illness within 4 weeks prior to the first dose of study medication; 4. Subject has used mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), mexrenone (mexrenoate potassium) within 4 weeks prior to the first dose of study medication; 5. Subject has evidence of symptomatic cardiomyopathy. \[Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary\]; 6. Subject is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents. \[Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 3 months cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis. Inhaled and/or topical corticosteroids prescribed for an indication other than DMD are permitted but must be administered at stable dose for at least 3 months prior to study drug administration\]; 7. Subject has used idebenone within 4 weeks prior to the first dose of study medication; 8. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents; 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 any other investigational drug currently or has taken any other investigational drug within 3 months prior to the start of study treatment; or 12. Subject has previously been enrolled in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Adverse events will be recorded from the date of informed consent and through the time of the subject's last study visit. Serious adverse events will be recorded from the date of informed consent and for up to 30 days after final drug administration. | Treatment-emergent adverse events (TEAEs) are defined as any adverse event or worsening of an existing conditions after initiation of the investigational product and through the subject's last study visit (study completion or early termination). Serious adverse events were recorded for up to 30 days after the final administration of study drug. Note: Total Number of Treatment Emergent Adverse Events: The total incidences of TEAEs experienced in study; Any Treatment Emergent Adverse Event: TEAEs reported at least once per dose group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose | Baseline, Week 2 | Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD. |
| Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Baseline , Week 2 | Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD. |
| Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol | Week 2 (pre-dose) | Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD. |
| Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Baseline, Day 1, Week 2, Week 4 | Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD. |
| Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Baseline Day 1 Week 2 Week 4 | Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD. |
| Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Baseline, Day 1, Week 4 | Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD. |
| Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Baseline, Week 2 | Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD. |
| Pharmacokinetic (PK) Assessments (AUC Inf) | Day 1, Week 2 | Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay. AUC inf= Area under the concentration vs. time curve to time infinity. |
| Pharmacokinetic (PK) Assessments CL (ml/hr/kg) | Day 1, Week 2 | Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay |
| Pharmacokinetic (PK) Assessments t(1/2) | Day 1, Week 2 | Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay. t1/2= elimination half life. |
| Pharmacokinetic (PK) Assessments (Cmax) | Day 1, Week 2 | Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay |
| Metabolites in Safety Testing (MIST) Assessment | Week 2 (Day 14) | A portion of each blood sample of the Week 2 (Day 14) pharmacokinetic assessment time points for the subjects receiving vamorolone 2 mg/kg/day was used for analysis of vamorolone metabolites. |
| Pharmacokinetic (PK) Assessments (Tmax) | Day 1, Week 2 | Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay. tmax= time when plasma concentration is at maximum. |
Countries
Australia, Canada, Israel, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level Group 1 Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day.
Vamorolone 0.25 mg/kg/day: Oral administration of 0.25 mg/kg/day daily for 14 days. | 12 |
| Dose Level Group 2 Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day.
Vamorolone 0.75 mg/kg/day: Oral administration of 0.75 mg/kg/day daily for 14 days. | 12 |
| Dose Level Group 3 Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day.
Vamorolone 2.0 mg/kg/day: Oral administration of 2.0 mg/kg/day daily for 14 days. | 12 |
| Dose Level Group 4 Participants enrolled in Dose Level Group 4 will receive vamorolone 6.0 mg/kg/day.
Vamorolone 6.0 mg/kg/day: Oral administration of 6 mg/kg/day daily for 14 days. | 12 |
| Total | 48 |
Baseline characteristics
| Characteristic | Dose Level Group 1 | Dose Level Group 2 | Dose Level Group 3 | Dose Level Group 4 | Total |
|---|---|---|---|---|---|
| Age, Customized Age | 5.2 years STANDARD_DEVIATION 1.03 | 4.8 years STANDARD_DEVIATION 0.83 | 4.7 years STANDARD_DEVIATION 0.89 | 4.8 years STANDARD_DEVIATION 0.75 | 4.9 years STANDARD_DEVIATION 0.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 11 Participants | 12 Participants | 9 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 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 |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 10 Participants | 12 Participants | 12 Participants | 45 Participants |
| Region of Enrollment Australia | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Region of Enrollment Canada | 3 Participants | 0 Participants | 2 Participants | 2 Participants | 7 Participants |
| Region of Enrollment Israel | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Region of Enrollment Sweden | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 4 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 0 Participants | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 9 Participants | 3 Participants | 2 Participants | 6 Participants | 20 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 12 Participants | 12 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 7 / 12 | 6 / 12 | 8 / 12 | 7 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03
Treatment-emergent adverse events (TEAEs) are defined as any adverse event or worsening of an existing conditions after initiation of the investigational product and through the subject's last study visit (study completion or early termination). Serious adverse events were recorded for up to 30 days after the final administration of study drug. Note: Total Number of Treatment Emergent Adverse Events: The total incidences of TEAEs experienced in study; Any Treatment Emergent Adverse Event: TEAEs reported at least once per dose group
Time frame: Adverse events will be recorded from the date of informed consent and through the time of the subject's last study visit. Serious adverse events will be recorded from the date of informed consent and for up to 30 days after final drug administration.
Population: Safety Population: All subjects who receive at least one dose of vamorolone study medication will be included in safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Level Group 1 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of Treatment Emergent Adverse Events | 13 Number of Events |
| Dose Level Group 1 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Treatment Emergent Adverse Events | 7 Number of Events |
| Dose Level Group 1 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Discontinuation of Study Drug due to TEAE | 0 Number of Events |
| Dose Level Group 1 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any CTCAE Grade 3 or Higher TEAE | 0 Number of Events |
| Dose Level Group 1 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Death | 0 Number of Events |
| Dose Level Group 1 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Drug Related Treatment Emergent Adverse Events | 1 Number of Events |
| Dose Level Group 1 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Serious Treatment Emergent Adverse Events | 0 Number of Events |
| Dose Level Group 1 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of Adverse Events | 16 Number of Events |
| Dose Level Group 2 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Death | 0 Number of Events |
| Dose Level Group 2 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any CTCAE Grade 3 or Higher TEAE | 0 Number of Events |
| Dose Level Group 2 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Discontinuation of Study Drug due to TEAE | 0 Number of Events |
| Dose Level Group 2 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of Treatment Emergent Adverse Events | 13 Number of Events |
| Dose Level Group 2 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of Adverse Events | 18 Number of Events |
| Dose Level Group 2 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Treatment Emergent Adverse Events | 6 Number of Events |
| Dose Level Group 2 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Serious Treatment Emergent Adverse Events | 0 Number of Events |
| Dose Level Group 2 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Drug Related Treatment Emergent Adverse Events | 2 Number of Events |
| Dose Level Group 3 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Discontinuation of Study Drug due to TEAE | 0 Number of Events |
| Dose Level Group 3 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Serious Treatment Emergent Adverse Events | 0 Number of Events |
| Dose Level Group 3 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of Treatment Emergent Adverse Events | 11 Number of Events |
| Dose Level Group 3 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Death | 0 Number of Events |
| Dose Level Group 3 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Treatment Emergent Adverse Events | 8 Number of Events |
| Dose Level Group 3 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of Adverse Events | 13 Number of Events |
| Dose Level Group 3 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Drug Related Treatment Emergent Adverse Events | 2 Number of Events |
| Dose Level Group 3 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any CTCAE Grade 3 or Higher TEAE | 0 Number of Events |
| Dose Level Group 4 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Drug Related Treatment Emergent Adverse Events | 3 Number of Events |
| Dose Level Group 4 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of Adverse Events | 11 Number of Events |
| Dose Level Group 4 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of Treatment Emergent Adverse Events | 9 Number of Events |
| Dose Level Group 4 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Treatment Emergent Adverse Events | 7 Number of Events |
| Dose Level Group 4 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Death | 0 Number of Events |
| Dose Level Group 4 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any CTCAE Grade 3 or Higher TEAE | 0 Number of Events |
| Dose Level Group 4 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Discontinuation of Study Drug due to TEAE | 0 Number of Events |
| Dose Level Group 4 | Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 | Any Serious Treatment Emergent Adverse Events | 0 Number of Events |
Secondary
Metabolites in Safety Testing (MIST) Assessment
A portion of each blood sample of the Week 2 (Day 14) pharmacokinetic assessment time points for the subjects receiving vamorolone 2 mg/kg/day was used for analysis of vamorolone metabolites.
Time frame: Week 2 (Day 14)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Metabolites in Safety Testing (MIST) Assessment | M1 | 34.42 % of total drug related exposure | Standard Deviation 2.79 |
| Dose Level Group 1 | Metabolites in Safety Testing (MIST) Assessment | M2 | 1.16 % of total drug related exposure | Standard Deviation 0.06 |
| Dose Level Group 1 | Metabolites in Safety Testing (MIST) Assessment | M3 | 1.21 % of total drug related exposure | Standard Deviation 0.07 |
| Dose Level Group 1 | Metabolites in Safety Testing (MIST) Assessment | M4 | 37.84 % of total drug related exposure | Standard Deviation 3.78 |
| Dose Level Group 1 | Metabolites in Safety Testing (MIST) Assessment | M5 | 2.73 % of total drug related exposure | Standard Deviation 0.17 |
| Dose Level Group 1 | Metabolites in Safety Testing (MIST) Assessment | Vamorolone | 22.64 % of total drug related exposure | Standard Deviation 0.69 |
Secondary
Pharmacokinetic (PK) Assessments (AUC Inf)
Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay. AUC inf= Area under the concentration vs. time curve to time infinity.
Time frame: Day 1, Week 2
Population: All subjects who receive at least one dose of vamorolone study medication and have sufficient quantifiable plasma concentration data for PK analysis will be included in the PK population. \[Note that the PK population will be determined by the study pharmacokineticist upon review of the concentration information for each subject in each cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments (AUC Inf) | Day 1 | 118 [(hr)(ng)/mL] | Standard Deviation 48 |
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments (AUC Inf) | Week 2 | 164 [(hr)(ng)/mL] | Standard Deviation 61 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments (AUC Inf) | Week 2 | 544 [(hr)(ng)/mL] | Standard Deviation 155 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments (AUC Inf) | Day 1 | 379 [(hr)(ng)/mL] | Standard Deviation 117 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments (AUC Inf) | Day 1 | 761 [(hr)(ng)/mL] | Standard Deviation 352 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments (AUC Inf) | Week 2 | 1138 [(hr)(ng)/mL] | Standard Deviation 467 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments (AUC Inf) | Day 1 | 3279 [(hr)(ng)/mL] | Standard Deviation 1693 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments (AUC Inf) | Week 2 | 3606 [(hr)(ng)/mL] | Standard Deviation 897 |
Secondary
Pharmacokinetic (PK) Assessments CL (ml/hr/kg)
Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay
Time frame: Day 1, Week 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments CL (ml/hr/kg) | Day 1 | 2459 ml/hr/kg | Standard Deviation 897 |
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments CL (ml/hr/kg) | Week 2 | 1828 ml/hr/kg | Standard Deviation 919 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments CL (ml/hr/kg) | Week 2 | 1509 ml/hr/kg | Standard Deviation 482 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments CL (ml/hr/kg) | Day 1 | 2285 ml/hr/kg | Standard Deviation 1103 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments CL (ml/hr/kg) | Day 1 | 2697 ml/hr/kg | Standard Deviation 1285 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments CL (ml/hr/kg) | Week 2 | 2047 ml/hr/kg | Standard Deviation 771 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments CL (ml/hr/kg) | Day 1 | 2320 ml/hr/kg | Standard Deviation 1375 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments CL (ml/hr/kg) | Week 2 | 1777 ml/hr/kg | Standard Deviation 476 |
Secondary
Pharmacokinetic (PK) Assessments (Cmax)
Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay
Time frame: Day 1, Week 2
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments (Cmax) | Day 1 | 22.9 ng/mL | Standard Deviation 13.4 |
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments (Cmax) | Week 2 | 32.2 ng/mL | Standard Deviation 15.2 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments (Cmax) | Week 2 | 124.7 ng/mL | Standard Deviation 42.5 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments (Cmax) | Day 1 | 75.9 ng/mL | Standard Deviation 25.9 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments (Cmax) | Day 1 | 199 ng/mL | Standard Deviation 111 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments (Cmax) | Week 2 | 252.2 ng/mL | Standard Deviation 96 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments (Cmax) | Day 1 | 855.6 ng/mL | Standard Deviation 471 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments (Cmax) | Week 2 | 970 ng/mL | Standard Deviation 270 |
Secondary
Pharmacokinetic (PK) Assessments t(1/2)
Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay. t1/2= elimination half life.
Time frame: Day 1, Week 2
Population: All subjects who receive at least one dose of vamorolone study medication and have sufficient quantifiable plasma concentration data for PK analysis will be included in the PK population. \[Note that the PK population will be determined by the study pharmacokineticist upon review of the concentration information for each subject in each cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments t(1/2) | Day 1 | 2.1 hour | Standard Deviation 0.85 |
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments t(1/2) | Week 2 | 1.9 hour | Standard Deviation 0.96 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments t(1/2) | Week 2 | 2.1 hour | Standard Deviation 0.8 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments t(1/2) | Day 1 | 1.8 hour | Standard Deviation 0.43 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments t(1/2) | Day 1 | 1.9 hour | Standard Deviation 0.79 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments t(1/2) | Week 2 | 1.9 hour | Standard Deviation 1.02 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments t(1/2) | Day 1 | 1.9 hour | Standard Deviation 0.95 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments t(1/2) | Week 2 | 1.4 hour | Standard Deviation 0.35 |
Secondary
Pharmacokinetic (PK) Assessments (Tmax)
Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay. tmax= time when plasma concentration is at maximum.
Time frame: Day 1, Week 2
Population: All subjects who receive at least one dose of vamorolone study medication and have sufficient quantifiable plasma concentration data for PK analysis will be included in the PK population. \[Note that the PK population will be determined by the study pharmacokineticist upon review of the concentration information for each subject in each cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments (Tmax) | Day 1 | 3.6 hour | Standard Deviation 1.2 |
| Dose Level Group 1 | Pharmacokinetic (PK) Assessments (Tmax) | Week 2 | 3.8 hour | Standard Deviation 1.8 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments (Tmax) | Week 2 | 3.8 hour | Standard Deviation 2.2 |
| Dose Level Group 2 | Pharmacokinetic (PK) Assessments (Tmax) | Day 1 | 4.6 hour | Standard Deviation 2.1 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments (Tmax) | Day 1 | 2.5 hour | Standard Deviation 1.3 |
| Dose Level Group 3 | Pharmacokinetic (PK) Assessments (Tmax) | Week 2 | 2.8 hour | Standard Deviation 1 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments (Tmax) | Day 1 | 2.7 hour | Standard Deviation 1.3 |
| Dose Level Group 4 | Pharmacokinetic (PK) Assessments (Tmax) | Week 2 | 2.3 hour | Standard Deviation 0.86 |
Secondary
Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Week 2 (pre-dose)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol | 10.425 mcg/dL | Standard Deviation 1.7358 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol | 9.755 mcg/dL | Standard Deviation 2.7614 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol | 7.321 mcg/dL | Standard Deviation 3.0322 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol | 3.010 mcg/dL | Standard Deviation 1.0141 |
Secondary
Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline Day 1 Week 2 Week 4
Population: Safety Population: All subjects who receive at least one dose of vamorolone study medication will be included in the Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Baseline | 555.8 ng/mL | Standard Deviation 184.72 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 | 573.8 ng/mL | Standard Deviation 251.02 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 Change from Baseline | -112.0 ng/mL | Standard Deviation 125.08 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 | 474.0 ng/mL | Standard Deviation 116.45 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 Change from Baseline | 18.1 ng/mL | Standard Deviation 153.1 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 Change from Baseline | -81.8 ng/mL | Standard Deviation 124.24 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 | 443.8 ng/mL | Standard Deviation 93.86 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 | 496.7 ng/mL | Standard Deviation 117.57 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 | 407.8 ng/mL | Standard Deviation 96.54 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 Change from Baseline | -34.5 ng/mL | Standard Deviation 101.97 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 Change from Baseline | -70.6 ng/mL | Standard Deviation 123.69 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 Change from Baseline | 21.3 ng/mL | Standard Deviation 122.87 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 | 443.7 ng/mL | Standard Deviation 112.38 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Baseline | 480.7 ng/mL | Standard Deviation 118.2 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 | 346.6 ng/mL | Standard Deviation 68.59 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Baseline | 508.2 ng/mL | Standard Deviation 94.36 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 | 417.1 ng/mL | Standard Deviation 87.35 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 Change from Baseline | -91.1 ng/mL | Standard Deviation 64.64 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 Change from Baseline | -161.6 ng/mL | Standard Deviation 73.52 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 | 492.0 ng/mL | Standard Deviation 81.92 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 Change from Baseline | -16.2 ng/mL | Standard Deviation 79.64 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 Change from Baseline | -36.5 ng/mL | Standard Deviation 144.04 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 Change from Baseline | 54.8 ng/mL | Standard Deviation 118.09 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 | 566.3 ng/mL | Standard Deviation 149.32 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 | 475.2 ng/mL | Standard Deviation 147.1 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Baseline | 511.5 ng/mL | Standard Deviation 106.5 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 Change from Baseline | -207.8 ng/mL | Standard Deviation 78.16 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 | 303.7 ng/mL | Standard Deviation 56.38 |
Secondary
Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline, Day 1, Week 2, Week 4
Population: Safety Population: All subjects who receive at least one dose of vamorolone study medication will be included in the Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 Percent Change from Baseline | -12.2 % change from Baseline | Standard Deviation 17.07 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 Percent Change from Baseline | 2.8 % change from Baseline | Standard Deviation 25.57 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 Percent Change from Baseline | -17.5 % change from Baseline | Standard Deviation 14.65 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 Percent Change from Baseline | -5.4 % change from Baseline | Standard Deviation 24.58 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 Percent Change from Baseline | 7.8 % change from Baseline | Standard Deviation 30.86 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 Percent Change from Baseline | -11.2 % change from Baseline | Standard Deviation 29.19 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 Percent Change from Baseline | -30.9 % change from Baseline | Standard Deviation 11.8 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 Percent Change from Baseline | -17.4 % change from Baseline | Standard Deviation 12.59 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 Percent Change from Baseline | -1.4 % change from Baseline | Standard Deviation 17.47 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Day 1 Percent Change from Baseline | -5.7 % change from Baseline | Standard Deviation 30.76 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 4 Percent Change from Baseline | 11.8 % change from Baseline | Standard Deviation 28.24 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide | Week 2 Percent Change from Baseline | -39.9 % change from Baseline | Standard Deviation 9.22 |
Secondary
Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline, Day 1, Week 4
Population: Safety Population: All subjects who receive at least one dose of vamorolone study medication will be included in the Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Baseline | 871.0 pg/mL | Standard Deviation 160.85 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 | 915.9 pg/mL | Standard Deviation 263.13 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 Change from Baseline | 85.0 pg/mL | Standard Deviation 185.9 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 | 974.8 pg/mL | Standard Deviation 252.77 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 Change from Baseline | 17.4 pg/mL | Standard Deviation 267.45 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 Change from Baseline | 72.4 pg/mL | Standard Deviation 241.87 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 | 963.7 pg/mL | Standard Deviation 157.68 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 | 983.5 pg/mL | Standard Deviation 298.47 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 | 903.3 pg/mL | Standard Deviation 251.01 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 Change from Baseline | -12.9 pg/mL | Standard Deviation 233.44 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 Change from Baseline | -19.9 pg/mL | Standard Deviation 266.99 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 Change from Baseline | 34.8 pg/mL | Standard Deviation 271.5 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 | 940.8 pg/mL | Standard Deviation 227.6 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Baseline | 935.8 pg/mL | Standard Deviation 286.5 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 | 710.4 pg/mL | Standard Deviation 180.03 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Baseline | 936.8 pg/mL | Standard Deviation 256.25 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 | 838.3 pg/mL | Standard Deviation 233.3 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 Change from Baseline | -98.5 pg/mL | Standard Deviation 237.69 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 Change from Baseline | -226.4 pg/mL | Standard Deviation 185.99 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 | 949.8 pg/mL | Standard Deviation 303.76 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 Change from Baseline | 12.9 pg/mL | Standard Deviation 181.45 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 Change from Baseline | -115.7 pg/mL | Standard Deviation 421.04 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 Change from Baseline | 99.8 pg/mL | Standard Deviation 211.9 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 | 989.2 pg/mL | Standard Deviation 216.29 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 | 786.8 pg/mL | Standard Deviation 331.68 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Baseline | 889.3 pg/mL | Standard Deviation 186.68 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 Change from Baseline | -263.7 pg/mL | Standard Deviation 229.69 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 | 625.7 pg/mL | Standard Deviation 203.19 |
Secondary
Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline, Day 1, Week 4
Population: Safety Population: All subjects who receive at least one dose of vamorolone study medication will be included in the Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 Percent Change from Baseline | 9.9 % change from Baseline | Standard Deviation 25.38 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 Percent Change from Baseline | 3.6 % change from Baseline | Standard Deviation 28.96 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 Percent Change from Baseline | 11.9 % change from Baseline | Standard Deviation 20.52 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 Percent Change from Baseline | 2.7 % change from Baseline | Standard Deviation 23.76 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 Percent Change from Baseline | 6.8 % change from Baseline | Standard Deviation 24.06 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 Percent Change from Baseline | 2.2 % change from Baseline | Standard Deviation 26.44 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 Percent Change from Baseline | -22.5 % change from Baseline | Standard Deviation 15.27 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 Percent Change from Baseline | -8.0 % change from Baseline | Standard Deviation 23.93 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 Percent Change from Baseline | 2.7 % change from Baseline | Standard Deviation 19.03 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Day 1 Percent Change from Baseline | -6.7 % change from Baseline | Standard Deviation 53.72 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 4 Percent Change from Baseline | 14.5 % change from Baseline | Standard Deviation 32.98 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides | Week 2 Percent Change from Baseline | -27.7 % change from Baseline | Standard Deviation 26.5 |
Secondary
Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline, Week 2
Population: Safety Population: All subject who receive at least dose of vamorolone study medication will be included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose | -1.8 Week 2 % change from Baseline | Standard Deviation 13.07 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose | -4.2 Week 2 % change from Baseline | Standard Deviation 13.98 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose | 0.8 Week 2 % change from Baseline | Standard Deviation 9.76 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose | -1.2 Week 2 % change from Baseline | Standard Deviation 9.8 |
Secondary
Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline, Week 2
Population: Safety Population: All subject who receive at least dose of vamorolone study medication will be included in the safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Baseline | 87.5 mg/ dL | Standard Deviation 9.44 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Week 2 Change from Baseline | -2.2 mg/ dL | Standard Deviation 10.46 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Week 2 | 85.3 mg/ dL | Standard Deviation 9.29 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Baseline | 88.9 mg/ dL | Standard Deviation 18.71 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Week 2 Change from Baseline | -5.8 mg/ dL | Standard Deviation 18.92 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Week 2 | 83.1 mg/ dL | Standard Deviation 6.69 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Week 2 | 89.5 mg/ dL | Standard Deviation 5.2 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Baseline | 89.3 mg/ dL | Standard Deviation 7.91 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Week 2 Change from Baseline | 0.2 mg/ dL | Standard Deviation 8.79 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Baseline | 92.3 mg/ dL | Standard Deviation 8.19 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Week 2 Change from Baseline | -1.3 mg/ dL | Standard Deviation 9.41 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose | Week 2 | 89.2 mg/ dL | Standard Deviation 11.12 |
Secondary
Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline, Week 2
Population: Safety Population All subjects who receive at least one dose of vamorolone study medication will be included in the Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | -5.54 Week 2 % change from Baseline | Standard Deviation 32.622 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | 26.07 Week 2 % change from Baseline | Standard Deviation 76.483 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | 42.85 Week 2 % change from Baseline | Standard Deviation 107.337 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | 83.55 Week 2 % change from Baseline | Standard Deviation 117.064 |
Secondary
Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline , Week 2
Population: Safety Population All subjects who receive at least one dose of vamorolone study medication will be included in the Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Baseline | 5.54 µIU/mL | Standard Deviation 3.651 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Week 2 Change from Baseline | -0.65 µIU/mL | Standard Deviation 2.913 |
| Dose Level Group 1 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Week 2 | 5.29 µIU/mL | Standard Deviation 2.671 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Baseline | 3.09 µIU/mL | Standard Deviation 2.033 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Week 2 Change from Baseline | 0.34 µIU/mL | Standard Deviation 1.289 |
| Dose Level Group 2 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Week 2 | 3.22 µIU/mL | Standard Deviation 1.924 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Week 2 | 3.87 µIU/mL | Standard Deviation 2.118 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Baseline | 3.40 µIU/mL | Standard Deviation 1.548 |
| Dose Level Group 3 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Week 2 Change from Baseline | 0.47 µIU/mL | Standard Deviation 2.777 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Baseline | 3.96 µIU/mL | Standard Deviation 2.027 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Week 2 Change from Baseline | 2.78 µIU/mL | Standard Deviation 4.651 |
| Dose Level Group 4 | Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin | Week 2 | 6.73 µIU/mL | Standard Deviation 4.599 |
Secondary
Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline, Day 1, Week 2, Week 4
Population: Safety Population: All subjects who receive at least one dose of vamorolone study medication will be included in the Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 Percent Change from Baseline | 3.95 % change from Baseline | Standard Deviation 22.015 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 Percent Change from Baseline | 2.72 % change from Baseline | Standard Deviation 14.063 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 Percent Change from Baseline | 2.48 % change from Baseline | Standard Deviation 16.756 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 Percent Change from Baseline | 1.41 % change from Baseline | Standard Deviation 15.449 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 Percent Change from Baseline | 20.91 % change from Baseline | Standard Deviation 28.644 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 Percent Change from Baseline | -0.07 % change from Baseline | Standard Deviation 22.408 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 Percent Change from Baseline | -7.81 % change from Baseline | Standard Deviation 23.664 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 Percent Change from Baseline | -12.63 % change from Baseline | Standard Deviation 25.02 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 Percent Change from Baseline | 18.74 % change from Baseline | Standard Deviation 25.095 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 Percent Change from Baseline | -25.05 % change from Baseline | Standard Deviation 20.228 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 Percent Change from Baseline | -2.43 % change from Baseline | Standard Deviation 25.932 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 Percent Change from Baseline | -33.87 % change from Baseline | Standard Deviation 12.548 |
Secondary
Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin
Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-\< 7 years with DMD.
Time frame: Baseline, Day 1, Week 2, Week 4
Population: Safety Population: All subjects who receive at least one dose of vamorolone study medication will be included in the Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Baseline | 37.94 ng/mL | Standard Deviation 11.622 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 | 39.20 ng/mL | Standard Deviation 14.136 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 Change from Baseline | 0.58 ng/mL | Standard Deviation 5.986 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 | 39.37 ng/mL | Standard Deviation 14.189 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 Change from Baseline | 1.26 ng/mL | Standard Deviation 5.65 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 Change from Baseline | 1.43 ng/mL | Standard Deviation 8.197 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 | 38.53 ng/mL | Standard Deviation 12.025 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 | 42.24 ng/mL | Standard Deviation 8.426 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 | 35.10 ng/mL | Standard Deviation 8.238 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 Change from Baseline | 0.23 ng/mL | Standard Deviation 5.304 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 Change from Baseline | -0.56 ng/mL | Standard Deviation 7.934 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 Change from Baseline | 6.58 ng/mL | Standard Deviation 9.341 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 | 35.89 ng/mL | Standard Deviation 7.526 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Baseline | 35.66 ng/mL | Standard Deviation 6.8 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 | 37.51 ng/mL | Standard Deviation 8.624 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Baseline | 41.17 ng/mL | Standard Deviation 5.617 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 | 34.93 ng/mL | Standard Deviation 6.881 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 Change from Baseline | -6.23 ng/mL | Standard Deviation 10.93 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 Change from Baseline | -3.66 ng/mL | Standard Deviation 9.818 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 | 47.91 ng/mL | Standard Deviation 6.648 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 Change from Baseline | 6.74 ng/mL | Standard Deviation 9.747 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 Change from Baseline | -11.37 ng/mL | Standard Deviation 9.137 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 Change from Baseline | -1.55 ng/mL | Standard Deviation 11.176 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 4 | 42.81 ng/mL | Standard Deviation 10.851 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Day 1 | 33.52 ng/mL | Standard Deviation 9.135 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Baseline | 44.36 ng/mL | Standard Deviation 5.979 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 Change from Baseline | -15.32 ng/mL | Standard Deviation 6.45 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin | Week 2 | 29.04 ng/mL | Standard Deviation 4.853 |