Duchenne Muscular Dystrophy
Conditions
Keywords
DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51
Brief summary
This is a multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, and PK of once-weekly IV infusions of eteplirsen in approximately 12 male participants, ages 6 months to 48 months (inclusive), who have genotypically confirmed DMD with a deletion mutation amenable to exon 51 skipping.
Interventions
DRUGEteplirsen
Infusion for intravenous use.
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
6 Months to 48 Months
Healthy volunteers
No
Inclusion criteria
* Male between 6 months to 48 months of age (inclusive) * Diagnosis of DMD with a deletion mutation amenable to exon 51 skipping * Parent(s) or legal guardian(s) who is willing to provide written informed consent
Exclusion criteria
* Received treatment that might have an effect on muscle strength or function within 12 weeks prior to dosing * Received previous or current treatment with any experimental treatment * Clinically significant illness other than DMD * Clinically significant laboratory abnormality * Any other condition that could interfere with the participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO) | Weeks 8, 12, 24, 36, 48, 60, 72, 84, 96 | The ECG was manually reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the centrally read ECG report were clinically significant. Clinical significance was defined as any variation in ECG findings that had medical relevance resulting in an alteration in medical care. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the ECHO report were clinically significant. Clinical significance was defined as any variation in ECHO findings that had medical relevance resulting in an alteration in medical care. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug | Baseline up to Week 100 | TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the study drug. Abnormalities presented at Baseline were considered AEs if they reoccurred after resolution or worsen during the AE collection period. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section. |
| Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality | Baseline up to Week 100 | Clinical laboratory parameters that were evaluated included * Any Grade ≥2 (moderate) or serious event without an alternative etiology that the Investigator deemed was related to study drug * Two consecutive drug-related serum creatinine levels ≥2\*upper limit of normal (ULN) without an alternative etiology * Creatine kinase (CK) levels \>50,000 units/liter (U/L) * A confirmed, unexplained, increase in gamma glutamyl transferase (GGT) \>3\*ULN and either an increase in bilirubin \>2\*ULN or nascent prothrombin time \>2\*ULN concurrently, without an alternative etiology |
| Number of Participants With at Least 1 Markedly Abnormal Vital Sign | Baseline up to Week 100 | The vital sign parameters that were evaluated included blood pressure, heart rate, respiration, and temperature. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section. |
| Abnormal Changes From Baseline or Worsening of Physical Examination Findings | Baseline up to Week 100 | Data not collected during the study for this Outcome Measure. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level) | — |
| Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level) | — |
| Amount of Drug Eliminated in Urine | Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level) | Amount of unchanged drug excreted in urine from time 0 to 4 hours after completion of dosing is reported. |
| Maximum Plasma Concentration (Cmax) of Eteplirsen | Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level) | — |
Countries
Belgium, France, Italy, United Kingdom
Participant flow
Pre-assignment details
Participants with genotypically confirmed Duchenne muscular dystrophy (DMD) featuring a deletion mutation amenable to exon 51 skipping were enrolled into 2 cohorts based on their age.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Eteplirsen was administered once every 7 days by IV infusion starting on Day 1 for up to 96 weeks. The starting dose was 2 mg/kg eteplirsen, with escalation to 4, 10, 20, and 30 mg/kg for 10 weeks, and then participants continued to receive eteplirsen at 30 mg/kg for the duration of the study. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 28.5 months STANDARD_DEVIATION 12.94 |
| Age, Customized 85 years and over | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants |
| Age, Customized Children (2-11 years) | 9 Participants |
| Age, Customized From 65-84 years | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 6 Participants |
| Age, Customized In utero | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 |
| other Total, other adverse events | 9 / 9 | 6 / 6 |
| serious Total, serious adverse events | 0 / 9 | 1 / 6 |
Outcome results
Primary
Abnormal Changes From Baseline or Worsening of Physical Examination Findings
Data not collected during the study for this Outcome Measure. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Time frame: Baseline up to Week 100
Population: The Safety Set included all participants who were enrolled and received at least 1 dose of eteplirsen during the study. Data were not collected for this Outcome Measure.
Primary
Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO)
The ECG was manually reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the centrally read ECG report were clinically significant. Clinical significance was defined as any variation in ECG findings that had medical relevance resulting in an alteration in medical care. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the ECHO report were clinically significant. Clinical significance was defined as any variation in ECHO findings that had medical relevance resulting in an alteration in medical care. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Time frame: Weeks 8, 12, 24, 36, 48, 60, 72, 84, 96
Population: The Safety Set included all participants who were enrolled and received at least 1 dose of eteplirsen during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Age 24 to 48 Months | Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO) | 4 Participants |
| Cohort 2: Age 6 to <24 Months | Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO) | 5 Participants |
Primary
Number of Participants With at Least 1 Markedly Abnormal Vital Sign
The vital sign parameters that were evaluated included blood pressure, heart rate, respiration, and temperature. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Time frame: Baseline up to Week 100
Population: The Safety Set included all participants who were enrolled and received at least 1 dose of eteplirsen during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Age 24 to 48 Months | Number of Participants With at Least 1 Markedly Abnormal Vital Sign | 9 Participants |
| Cohort 2: Age 6 to <24 Months | Number of Participants With at Least 1 Markedly Abnormal Vital Sign | 6 Participants |
Primary
Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality
Clinical laboratory parameters that were evaluated included * Any Grade ≥2 (moderate) or serious event without an alternative etiology that the Investigator deemed was related to study drug * Two consecutive drug-related serum creatinine levels ≥2\*upper limit of normal (ULN) without an alternative etiology * Creatine kinase (CK) levels \>50,000 units/liter (U/L) * A confirmed, unexplained, increase in gamma glutamyl transferase (GGT) \>3\*ULN and either an increase in bilirubin \>2\*ULN or nascent prothrombin time \>2\*ULN concurrently, without an alternative etiology
Time frame: Baseline up to Week 100
Population: The Safety Set included all participants who were enrolled and received at least 1 dose of eteplirsen during the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Age 24 to 48 Months | Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality | 9 Participants |
| Cohort 2: Age 6 to <24 Months | Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality | 6 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the study drug. Abnormalities presented at Baseline were considered AEs if they reoccurred after resolution or worsen during the AE collection period. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Time frame: Baseline up to Week 100
Population: The Safety Set included all participants who were enrolled and received at least 1 dose of eteplirsen during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Age 24 to 48 Months | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug | TEAE | 9 Participants |
| Cohort 1: Age 24 to 48 Months | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug | SAE | 0 Participants |
| Cohort 1: Age 24 to 48 Months | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug | AE leading to discontinuation from study drug | 0 Participants |
| Cohort 2: Age 6 to <24 Months | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug | TEAE | 6 Participants |
| Cohort 2: Age 6 to <24 Months | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug | SAE | 1 Participants |
| Cohort 2: Age 6 to <24 Months | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug | AE leading to discontinuation from study drug | 0 Participants |
Secondary
Amount of Drug Eliminated in Urine
Amount of unchanged drug excreted in urine from time 0 to 4 hours after completion of dosing is reported.
Time frame: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Population: The Safety Set was used for PK analysis and included all participants who were enrolled and received at least 1 dose of eteplirsen during the study. PK data were not collected for participants who received 4 mg of eteplirsen. Here, 'Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies number of participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Age 24 to 48 Months | Amount of Drug Eliminated in Urine | 10 mg/kg (Week 6) | 56000 μg | Standard Deviation 73300 |
| Cohort 1: Age 24 to 48 Months | Amount of Drug Eliminated in Urine | 30 mg/kg (Week 10) | 263000 μg | Standard Deviation 209000 |
| Cohort 1: Age 24 to 48 Months | Amount of Drug Eliminated in Urine | 20 mg/kg (Week 8) | 102000 μg | Standard Deviation 108000 |
| Cohort 1: Age 24 to 48 Months | Amount of Drug Eliminated in Urine | 30 mg/kg (Week 24) | 239000 μg | Standard Deviation 140000 |
| Cohort 1: Age 24 to 48 Months | Amount of Drug Eliminated in Urine | 2 mg/kg dose (Week 2) | 7720 μg | Standard Deviation 9060 |
| Cohort 2: Age 6 to <24 Months | Amount of Drug Eliminated in Urine | 30 mg/kg (Week 24) | 147000 μg | Standard Deviation 132000 |
| Cohort 2: Age 6 to <24 Months | Amount of Drug Eliminated in Urine | 2 mg/kg dose (Week 2) | 1430 μg | Standard Deviation 1390 |
| Cohort 2: Age 6 to <24 Months | Amount of Drug Eliminated in Urine | 10 mg/kg (Week 6) | 28700 μg | Standard Deviation 24100 |
| Cohort 2: Age 6 to <24 Months | Amount of Drug Eliminated in Urine | 20 mg/kg (Week 8) | 65600 μg | Standard Deviation 47900 |
| Cohort 2: Age 6 to <24 Months | Amount of Drug Eliminated in Urine | 30 mg/kg (Week 10) | 94700 μg | Standard Deviation 68500 |
Secondary
Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma
Time frame: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Population: The Safety Set was used for PK analysis and included all participants who were enrolled and received at least 1 dose of eteplirsen during the study. PK data were not collected for participants who received 4 mg of eteplirsen. Here, 'Number Analyzed' signifies number of participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Age 24 to 48 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 10 mg/kg (Week 6) | 56.1 μg*hr/mL | Geometric Coefficient of Variation 57.2 |
| Cohort 1: Age 24 to 48 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 30 mg/kg (Week 10) | 119 μg*hr/mL | Geometric Coefficient of Variation 30.8 |
| Cohort 1: Age 24 to 48 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 20 mg/kg (Week 8) | 92.1 μg*hr/mL | Geometric Coefficient of Variation 94.7 |
| Cohort 1: Age 24 to 48 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 30 mg/kg (Week 24) | 100 μg*hr/mL | Geometric Coefficient of Variation 42.5 |
| Cohort 1: Age 24 to 48 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 2 mg/kg (Week 2) | 13.8 μg*hr/mL | Geometric Coefficient of Variation 118 |
| Cohort 2: Age 6 to <24 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 30 mg/kg (Week 24) | 89.6 μg*hr/mL | Geometric Coefficient of Variation 43.8 |
| Cohort 2: Age 6 to <24 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 2 mg/kg (Week 2) | 6.13 μg*hr/mL | Geometric Coefficient of Variation 73.1 |
| Cohort 2: Age 6 to <24 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 10 mg/kg (Week 6) | 27.8 μg*hr/mL | Geometric Coefficient of Variation 113 |
| Cohort 2: Age 6 to <24 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 20 mg/kg (Week 8) | 81.4 μg*hr/mL | Geometric Coefficient of Variation 89.6 |
| Cohort 2: Age 6 to <24 Months | Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma | 30 mg/kg (Week 10) | 85.0 μg*hr/mL | Geometric Coefficient of Variation 114 |
Secondary
Maximum Plasma Concentration (Cmax) of Eteplirsen
Time frame: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Population: The Safety Set was used for pharmacokinetic(s) (PK) analysis and included all participants who were enrolled and received at least 1 dose of eteplirsen during the study. PK data were not collected for participants who received 4 mg of eteplirsen. Here, 'Number Analyzed' signifies number of participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Age 24 to 48 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 6 (10 mg/kg) | 46.5 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 72.3 |
| Cohort 1: Age 24 to 48 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 10 (30 mg/kg) | 93.7 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 55.5 |
| Cohort 1: Age 24 to 48 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 8 (20 mg/kg) | 63.3 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 123 |
| Cohort 1: Age 24 to 48 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 24 (30 mg/kg) | 78.2 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 92.2 |
| Cohort 1: Age 24 to 48 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 2 (2 mg/kg) | 9.67 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 75.9 |
| Cohort 2: Age 6 to <24 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 24 (30 mg/kg) | 59.7 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 82.7 |
| Cohort 2: Age 6 to <24 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 2 (2 mg/kg) | 4.22 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 120 |
| Cohort 2: Age 6 to <24 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 6 (10 mg/kg) | 17.2 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 192 |
| Cohort 2: Age 6 to <24 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 8 (20 mg/kg) | 85.0 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 67.6 |
| Cohort 2: Age 6 to <24 Months | Maximum Plasma Concentration (Cmax) of Eteplirsen | Week 10 (30 mg/kg) | 63.8 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 124 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen
Time frame: Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Population: The Safety Set was used for PK analysis and included all participants who were enrolled and received at least 1 dose of eteplirsen during the study. PK data were not collected for participants who received 4 mg of eteplirsen. Here, 'Number Analyzed' signifies number of participants evaluable at the specified timepoint.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Age 24 to 48 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 10 mg/kg (Week 6) | 0.58 hours (hr) |
| Cohort 1: Age 24 to 48 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 30 mg/kg (Week 10) | 0.58 hours (hr) |
| Cohort 1: Age 24 to 48 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 20 mg/kg (Week 8) | 0.78 hours (hr) |
| Cohort 1: Age 24 to 48 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 30 mg/kg (Week 24) | 0.63 hours (hr) |
| Cohort 1: Age 24 to 48 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 2 mg/kg (Week 2) | 0.58 hours (hr) |
| Cohort 2: Age 6 to <24 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 30 mg/kg (Week 24) | 0.72 hours (hr) |
| Cohort 2: Age 6 to <24 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 2 mg/kg (Week 2) | 0.58 hours (hr) |
| Cohort 2: Age 6 to <24 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 10 mg/kg (Week 6) | 0.72 hours (hr) |
| Cohort 2: Age 6 to <24 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 20 mg/kg (Week 8) | 0.73 hours (hr) |
| Cohort 2: Age 6 to <24 Months | Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen | 30 mg/kg (Week 10) | 0.92 hours (hr) |