Seizures
Conditions
Keywords
Lennox-Gastaut syndrome, Dravet syndrome, Treatment-resistant seizures
Brief summary
This is a multicenter, open-label trial to assess the long-term safety and efficacy of Cannabidiol Oral Solution as adjunctive therapy for pediatric participants with treatment-resistant seizure disorders, including Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS). All participants have rolled over from previous trials: INS011-14-029 (NCT02324673) and INS011-15-054 (NCT02551731).
Interventions
An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).
Sponsors
INSYS Therapeutics Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Completed activities through Day 11 in INS011-14-029 or Part A (Visit 6) INS011-15-054 * Informed consent/assent (as applicable) was voluntarily provided by the participant and/or parent(s)/caregiver(s) in accordance with applicable laws, regulations, and local requirements * Is medically stable with no anticipated changes in chronic medications in the opinion of the Investigator * Continues to meet protocol-specified criteria for qualification and contraception, including treatment-resistant seizure disorder * In the opinion of the Investigator, the subject and/or parent(s)/caregiver(s) are able to continue keeping accurate seizure diaries
Exclusion criteria
* Inadequate supervision by parent(s)/caregiver(s) * History or current use of dietary supplements, drugs or over-the counter medications outside protocol-specified parameters * Signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise: 1. the safety or well-being of the participant or study staff 2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding) 3. the analysis of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Plasma Levels of Cannabidiol and Its 7-OH Metabolite | Up to Week 50 | — |
| Percentage of Participants With Adverse Events | Up to Week 50 | An Adverse Event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product. It does not necessarily have a causal relationship with this treatment. |
| Percentage of Participants With Serious Adverse Events | Up to Week 50 | A serious adverse event is any untoward medical occurrence ( whether considered to be related to investigational product or not) that at any dose results in death, is life threatening, requires inpatient hospitalization, results in disability/incapacity, is a congenital abnormality/ birth defect, or medically significant as determined by an investigator. |
| Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Up to Week 50 | Laboratory values include chemistry and hematology, and urinary analysis. |
| Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | Up to Week 48 | — |
| Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs | Up to Week 50 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vineland Adaptive Behavior Scales (VABS) | Up to Week 48 | The Vineland Adaptive Behavior Scales measures the personal and social skills of individuals from birth through adulthood. Because adaptive behavior refers to an individual's typical performance of the day-to-day activities required for personal and social sufficiency, these scales assess what a person actually does, rather than what he or she is able to do. The Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) is a measure of adaptive behavior in children, adolescents and adults. It yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. The 4 domains are Communication, Daily Living Skills, Motor Skills, and Maladaptive Behaviour Index. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning. A rise in standard scores from Baseline indicates improvement. The VABS will be completed for all participants. |
| Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) | Up to Week 50 | For subjects 7 years of developmental age or older, the Columbia-Suicide Severity Rating Scale (C-SSRS) will be administered to access suicidality. The appropriate adult version will be used in subjects 12 years of (developmental) age and older. The investigator will determine the participant's developmental age. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression of Severity (CGI-S) | through study completion, up to 48 weeks or marketing approval, whichever is earlier | The severity of the participant's illness is rated on a seven-point scale, where 1=normal, not at all ill, and 7=among the most extremely ill patients. This rating is based upon observed and reported symptoms, behavior, and function in the past seven days. The score reflects the average severity level across the seven days. The CGI-S will be completed for all participants, regardless of chronological and developmental age. |
| Impact of Pediatric Epilepsy Scale (IPES) | through study completion, up to 48 weeks or marketing approval, whichever is earlier | The IPES assesses the impact on academic achievement, participation in activities, health, relationships with family and with peers and siblings, social activities, self-esteem, and the caregiver's hopes for their child's future. It takes about 3 minutes for the parent to complete. Each of the 11 items is given a severity score of 0 (not at all) to 3 (a lot). The higher the score, the higher is the impact of epilepsy on that item. The highest total score possible is 33 (range 0-33). The Impact of Pediatric Epilepsy Scale (IPES) is validated for subjects who are 2 to 16 years of age. Due to developmental delay characteristic of the study population, subjects through 18 years of chronological age will complete the IPES. Subjects over 18 years of chronological age will not complete the IPES. |
| Clinical Global Impression of Improvement (CGI-I) | through study completion, up to 48 weeks or marketing approval, whichever is earlier | The participant's overall clinical condition is compared to the one week period just before the start of medication (the baseline visit). The participant's condition is compared to the patient's condition at admission to the project \[prior to starting treatment\] on a 7-point scale, where 1=very much improved since the initiation of treatment; and 7=very much worse since the initiation of treatment. The CGI-I will be completed for all participants, regardless of chronological and developmental age. |
| Change From Baseline in Frequency of Seizures as a Measure of Seizure Control | through study completion, up to 48 weeks or marketing approval, whichever is earlier | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infants Participants 1 to \<2 years of age.Participants who completed INS011-14-029 initiated this study on the dose with which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant.
Participants who enrolled from INS011-15-054 continued treatment with the dose at which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant.
The total daily dose (mg/kg/day) will be evenly split between morning and evening doses (12 hours apart). If tolerability issues arise, the participant's dose may be changed at the investigator's discretion. | 9 |
| Children Participants 2 to \<12 years of age.Participants who completed INS011-14-029 initiated this study on the dose with which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant.
Participants who enrolled from INS011-15-054 continued treatment with the dose at which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant.
The total daily dose (mg/kg/day) will be evenly split between morning and evening doses (12 hours apart). If tolerability issues arise, the participant's dose may be changed at the investigator's discretion. | 26 |
| Adolescents Participants 12 to \<17 years of age.Participants who completed INS011-14-029 initiated this study on the dose with which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant.
Participants who enrolled from INS011-15-054 continued treatment with the dose at which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant.
The total daily dose (mg/kg/day) will be evenly split between morning and evening doses (12 hours apart). If tolerability issues arise, the participant's dose may be changed at the investigator's discretion. | 17 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Guardian decision to withdraw | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Infants | Total | Adolescents | Children |
|---|---|---|---|---|
| Age, Continuous | 1.00 Years STANDARD_DEVIATION 0 | 8.1 Years STANDARD_DEVIATION 5.07 | 13.9 Years STANDARD_DEVIATION 1.58 | 6.7 Years STANDARD_DEVIATION 2.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 47 Participants | 16 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 8 Participants | 43 Participants | 16 Participants | 19 Participants |
| Region of Enrollment United States | 9 participants | 52 participants | 17 participants | 26 participants |
| Sex: Female, Male Female | 4 Participants | 24 Participants | 9 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 28 Participants | 8 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 9 | 0 / 26 | 0 / 17 |
| other Total, other adverse events | 8 / 9 | 24 / 26 | 15 / 17 |
| serious Total, serious adverse events | 7 / 9 | 10 / 26 | 0 / 17 |
Outcome results
Primary
Change From Baseline in Trough Plasma Levels of Cannabidiol and Its 7-OH Metabolite
Time frame: Up to Week 50
Population: Insufficient data was collected to perform study analysis.
Primary
Percentage of Participants With Adverse Events
An Adverse Event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product. It does not necessarily have a causal relationship with this treatment.
Time frame: Up to Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infants | Percentage of Participants With Adverse Events | 88.9 Percentage of participants |
| Children | Percentage of Participants With Adverse Events | 92.3 Percentage of participants |
| Adolescents | Percentage of Participants With Adverse Events | 88.2 Percentage of participants |
| All Participants | Percentage of Participants With Adverse Events | 90.4 Percentage of participants |
Primary
Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings
Time frame: Up to Week 48
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infants | Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Percentage of participants |
| Children | Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Percentage of participants |
| Adolescents | Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Percentage of participants |
Primary
Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values
Laboratory values include chemistry and hematology, and urinary analysis.
Time frame: Up to Week 50
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infants | Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Blood Chemistry | 0 Percentage of participants |
| Infants | Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Hematology | 0 Percentage of participants |
| Infants | Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Urinalysis | 0 Percentage of participants |
| Children | Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Blood Chemistry | 0 Percentage of participants |
| Children | Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Hematology | 0 Percentage of participants |
| Children | Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Urinalysis | 0 Percentage of participants |
| Adolescents | Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Hematology | 0 Percentage of participants |
| Adolescents | Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Urinalysis | 0 Percentage of participants |
| Adolescents | Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Blood Chemistry | 0 Percentage of participants |
Primary
Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Up to Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infants | Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Percentage of participants |
| Children | Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Percentage of participants |
| Adolescents | Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Percentage of participants |
Primary
Percentage of Participants With Serious Adverse Events
A serious adverse event is any untoward medical occurrence ( whether considered to be related to investigational product or not) that at any dose results in death, is life threatening, requires inpatient hospitalization, results in disability/incapacity, is a congenital abnormality/ birth defect, or medically significant as determined by an investigator.
Time frame: Up to Week 50
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Infants | Percentage of Participants With Serious Adverse Events | 77.8 Percentage of participants |
| Children | Percentage of Participants With Serious Adverse Events | 38.5 Percentage of participants |
| Adolescents | Percentage of Participants With Serious Adverse Events | 0 Percentage of participants |
| All Participants | Percentage of Participants With Serious Adverse Events | 32.7 Percentage of participants |
Secondary
Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS)
For subjects 7 years of developmental age or older, the Columbia-Suicide Severity Rating Scale (C-SSRS) will be administered to access suicidality. The appropriate adult version will be used in subjects 12 years of (developmental) age and older. The investigator will determine the participant's developmental age.
Time frame: Up to Week 50
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Infants | Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Infants | Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
| Children | Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Children | Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
| Adolescents | Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Ideation | 0 Participants |
| Adolescents | Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) | Suicidal Behavior | 0 Participants |
Secondary
Vineland Adaptive Behavior Scales (VABS)
The Vineland Adaptive Behavior Scales measures the personal and social skills of individuals from birth through adulthood. Because adaptive behavior refers to an individual's typical performance of the day-to-day activities required for personal and social sufficiency, these scales assess what a person actually does, rather than what he or she is able to do. The Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) is a measure of adaptive behavior in children, adolescents and adults. It yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. The 4 domains are Communication, Daily Living Skills, Motor Skills, and Maladaptive Behaviour Index. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning. A rise in standard scores from Baseline indicates improvement. The VABS will be completed for all participants.
Time frame: Up to Week 48
Population: The Safety Analysis Population (SAF) consisted of all participants in the enrolled population group (ENR) who received at least one dose of the investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infants | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Fine (Day 1) | 4.2 Score on a scale | Standard Deviation 9.72 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Domestic (Week 48) | 0.8 Score on a scale | Standard Deviation 2.12 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Internalizing (Wk 48) | 1.0 Score on a scale | Standard Deviation 2 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Socialization: Play and Leisure Time (Week 48) | 6.4 Score on a scale | Standard Deviation 10.16 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Personal (Day 1) | 3.6 Score on a scale | Standard Deviation 6.65 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Communication: Receptive (Week 48) | 11.5 Score on a scale | Standard Deviation 8.73 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Socialization: Play and Leisure Time (Week 36) | 6.6 Score on a scale | Standard Deviation 10.55 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Personal (Week 36) | 5.0 Score on a scale | Standard Deviation 8.93 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Communication: Expressive (Day 1) | 6.8 Score on a scale | Standard Deviation 7.34 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Socialization: Play and Leisure Time (Day 1) | 5.3 Score on a scale | Standard Deviation 9.53 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Personal (Week 48) | 5.6 Score on a scale | Standard Deviation 8.09 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Internalizing (Wk 36) | 0.0 Score on a scale | Standard Deviation 0 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Socialization: Interpersonal Relationships (Wk 48) | 14.0 Score on a scale | Standard Deviation 12.62 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Socialization: Coping Skills (Day 1) | 2.1 Score on a scale | Standard Deviation 2.67 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Communication: Written (Day 1) | 0.0 Score on a scale | Standard Deviation 0 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Socialization: Interpersonal Relationships (Wk 36) | 11.9 Score on a scale | Standard Deviation 10.67 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Socialization: Coping Skills (Week 36) | 2.6 Score on a scale | Standard Deviation 3.99 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Communication: Expressive (Week 48) | 9.9 Score on a scale | Standard Deviation 9.3 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Socialization: Interpersonal Relationships (Day 1) | 9.4 Score on a scale | Standard Deviation 10.14 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Socialization: Coping Skills (Week 48) | 3.1 Score on a scale | Standard Deviation 4.32 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Externalizing (Wk 48) | 0.0 Score on a scale | Standard Deviation 0 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Communication: Written (Week 36) | 1.3 Score on a scale | Standard Deviation 2.31 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Communication: Expressive (Week 36) | 8.3 Score on a scale | Standard Deviation 9.03 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Externalizing (Wk 36) | 0.0 Score on a scale | Standard Deviation 0 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Communication: Written (Week 48) | 0.0 Score on a scale | Standard Deviation 0 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: MBI Score (Week 48) | 1.0 Score on a scale | Standard Deviation 2 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Gross (Week 48) | 12.8 Score on a scale | Standard Deviation 22.42 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Community (Day 1) | 0.4 Score on a scale | Standard Deviation 1.33 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Communication: Receptive (Day 1) | 6.0 Score on a scale | Standard Deviation 7.35 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Gross (Week 36) | 11.0 Score on a scale | Standard Deviation 22.96 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Community (Week 36) | 0.6 Score on a scale | Standard Deviation 1.51 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Other (Week 48) | 0.0 Score on a scale | Standard Deviation 0 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Gross (Day 1) | 8.0 Score on a scale | Standard Deviation 18.45 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Community (Week 48) | 1.0 Score on a scale | Standard Deviation 2.14 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: MBI Score (Week 36) | 0.0 Score on a scale | Standard Deviation 0 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Fine (Week 48) | 6.0 Score on a scale | Standard Deviation 8.67 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Domestic (Day 1) | 0.4 Score on a scale | Standard Deviation 1.33 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Communication: Receptive (Week 36) | 8.6 Score on a scale | Standard Deviation 7.23 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Fine (Week 36) | 5.1 Score on a scale | Standard Deviation 12.29 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Domestic (Week 36) | 0.9 Score on a scale | Standard Deviation 2.27 |
| Infants | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Other (Week 36) | 0.0 Score on a scale | Standard Deviation 0 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Communication: Receptive (Week 48) | 20.6 Score on a scale | Standard Deviation 13.15 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Communication: Expressive (Day 1) | 40.4 Score on a scale | Standard Deviation 37.53 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Communication: Expressive (Week 36) | 51.7 Score on a scale | Standard Deviation 41.79 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Communication: Expressive (Week 48) | 48.6 Score on a scale | Standard Deviation 38.91 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Communication: Receptive (Day 1) | 17.4 Score on a scale | Standard Deviation 13.1 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Communication: Receptive (Week 36) | 21.1 Score on a scale | Standard Deviation 13.15 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Communication: Written (Day 1) | 9.2 Score on a scale | Standard Deviation 13.47 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Communication: Written (Week 36) | 11.8 Score on a scale | Standard Deviation 15.98 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Communication: Written (Week 48) | 10.8 Score on a scale | Standard Deviation 13.88 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Community (Day 1) | 13.8 Score on a scale | Standard Deviation 18.62 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Community (Week 36) | 17.8 Score on a scale | Standard Deviation 19.99 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Community (Week 48) | 16.6 Score on a scale | Standard Deviation 21.29 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Domestic (Day 1) | 9.1 Score on a scale | Standard Deviation 11.85 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Domestic (Week 36) | 9.6 Score on a scale | Standard Deviation 12.45 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Domestic (Week 48) | 9.9 Score on a scale | Standard Deviation 13.43 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Personal (Day 1) | 31.7 Score on a scale | Standard Deviation 29.37 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Personal (Week 36) | 39.2 Score on a scale | Standard Deviation 29.64 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Personal (Week 48) | 36.2 Score on a scale | Standard Deviation 30.66 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Socialization: Coping Skills (Day 1) | 14.6 Score on a scale | Standard Deviation 18.34 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Socialization: Coping Skills (Week 36) | 16.2 Score on a scale | Standard Deviation 16.37 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Socialization: Coping Skills (Week 48) | 15.0 Score on a scale | Standard Deviation 17.08 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Socialization: Interpersonal Relationships (Day 1) | 28.9 Score on a scale | Standard Deviation 22.93 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Socialization: Interpersonal Relationships (Wk 36) | 35.7 Score on a scale | Standard Deviation 21.85 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Socialization: Interpersonal Relationships (Wk 48) | 33.3 Score on a scale | Standard Deviation 22.67 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Socialization: Play and Leisure Time (Day 1) | 20.5 Score on a scale | Standard Deviation 20.11 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Socialization: Play and Leisure Time (Week 36) | 24.4 Score on a scale | Standard Deviation 19.77 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Socialization: Play and Leisure Time (Week 48) | 21.8 Score on a scale | Standard Deviation 18.96 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Fine (Day 1) | 26.7 Score on a scale | Standard Deviation 27.29 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Fine (Week 36) | 33.6 Score on a scale | Standard Deviation 27.38 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Fine (Week 48) | 32.2 Score on a scale | Standard Deviation 27.56 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Gross (Day 1) | 42.5 Score on a scale | Standard Deviation 31.9 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Gross (Week 36) | 46.5 Score on a scale | Standard Deviation 32.43 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Gross (Week 48) | 46.6 Score on a scale | Standard Deviation 32.44 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Externalizing (Day 1) | 3.5 Score on a scale | Standard Deviation 3.51 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Externalizing (Wk 36) | 4.5 Score on a scale | Standard Deviation 4.81 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Externalizing (Wk 48) | 4.4 Score on a scale | Standard Deviation 4.1 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Internalizing (Day 1) | 5.2 Score on a scale | Standard Deviation 4.01 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Internalizing (Wk 36) | 5.4 Score on a scale | Standard Deviation 3.06 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Internalizing (Wk 48) | 5.3 Score on a scale | Standard Deviation 4.1 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: MBI Score (Day 1) | 14.8 Score on a scale | Standard Deviation 7.53 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: MBI Score (Week 36) | 16.6 Score on a scale | Standard Deviation 8.65 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: MBI Score (Week 48) | 16.1 Score on a scale | Standard Deviation 9.17 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Other (Day 1) | 6.2 Score on a scale | Standard Deviation 4.17 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Other (Week 36) | 6.7 Score on a scale | Standard Deviation 4.01 |
| Children | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Other (Week 48) | 6.5 Score on a scale | Standard Deviation 3.3 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Fine (Week 36) | 20.9 Score on a scale | Standard Deviation 24.32 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Community (Week 48) | 18.8 Score on a scale | Standard Deviation 29.07 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Communication: Expressive (Week 36) | 36.0 Score on a scale | Standard Deviation 41.63 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Fine (Week 48) | 24.0 Score on a scale | Standard Deviation 25.21 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Community (Week 36) | 18.8 Score on a scale | Standard Deviation 26.58 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: MBI Score (Day 1) | 13.0 Score on a scale | Standard Deviation 8.75 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Gross (Day 1) | 31.0 Score on a scale | Standard Deviation 29.57 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Community (Day 1) | 19.1 Score on a scale | Standard Deviation 26.03 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Communication: Receptive (Day 1) | 18.8 Score on a scale | Standard Deviation 14.88 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Gross (Week 36) | 31.9 Score on a scale | Standard Deviation 26.74 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Communication: Written (Week 48) | 10.5 Score on a scale | Standard Deviation 17.15 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Other (Week 48) | 4.3 Score on a scale | Standard Deviation 3.88 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Gross (Week 48) | 33.3 Score on a scale | Standard Deviation 29.03 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: MBI Score (Week 36) | 10.8 Score on a scale | Standard Deviation 9.04 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Externalizing (Day 1) | 3.5 Score on a scale | Standard Deviation 3.1 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Communication: Written (Week 36) | 12.8 Score on a scale | Standard Deviation 17.33 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Communication: Expressive (Week 48) | 34.3 Score on a scale | Standard Deviation 40.62 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Externalizing (Wk 36) | 3.1 Score on a scale | Standard Deviation 3.42 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Communication: Written (Day 1) | 12.9 Score on a scale | Standard Deviation 17.09 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Other (Week 36) | 4.1 Score on a scale | Standard Deviation 3.6 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Externalizing (Wk 48) | 2.2 Score on a scale | Standard Deviation 2.95 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Socialization: Coping Skills (Week 48) | 15.9 Score on a scale | Standard Deviation 20.63 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Socialization: Coping Skills (Week 36) | 16.7 Score on a scale | Standard Deviation 20.81 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: MBI Score (Week 48) | 10.2 Score on a scale | Standard Deviation 8.47 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Socialization: Interpersonal Relationships (Day 1) | 31.1 Score on a scale | Standard Deviation 25.41 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Socialization: Coping Skills (Day 1) | 16.9 Score on a scale | Standard Deviation 20.33 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Internalizing (Day 1) | 3.6 Score on a scale | Standard Deviation 3.24 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Socialization: Interpersonal Relationships (Wk 36) | 25.8 Score on a scale | Standard Deviation 22.75 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Personal (Week 48) | 25.4 Score on a scale | Standard Deviation 29.78 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Communication: Receptive (Week 48) | 16.8 Score on a scale | Standard Deviation 14.62 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Socialization: Interpersonal Relationships (Wk 48) | 26.7 Score on a scale | Standard Deviation 24.35 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Personal (Week 36) | 26.2 Score on a scale | Standard Deviation 29.19 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Communication: Expressive (Day 1) | 40.3 Score on a scale | Standard Deviation 42.76 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Socialization: Play and Leisure Time (Day 1) | 19.7 Score on a scale | Standard Deviation 20.62 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Personal (Day 1) | 28.6 Score on a scale | Standard Deviation 27.98 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Internalizing (Wk 36) | 3.7 Score on a scale | Standard Deviation 3.63 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Socialization: Play and Leisure Time (Week 36) | 19.6 Score on a scale | Standard Deviation 22.71 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Domestic (Week 48) | 9.2 Score on a scale | Standard Deviation 15.71 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Communication: Receptive (Week 36) | 15.7 Score on a scale | Standard Deviation 15.95 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Socialization: Play and Leisure Time (Week 48) | 17.9 Score on a scale | Standard Deviation 22.66 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Domestic (Week 36) | 10.7 Score on a scale | Standard Deviation 16.42 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Other (Day 1) | 6.2 Score on a scale | Standard Deviation 4.76 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Motor Skills: Fine (Day 1) | 23.1 Score on a scale | Standard Deviation 26.2 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Daily Living Skills: Domestic (Day 1) | 9.7 Score on a scale | Standard Deviation 15.7 |
| Adolescents | Vineland Adaptive Behavior Scales (VABS) | Maladaptive Behavior Index: Internalizing (Wk 48) | 3.6 Score on a scale | Standard Deviation 3.62 |
Other Pre-specified
Change From Baseline in Frequency of Seizures as a Measure of Seizure Control
Time frame: through study completion, up to 48 weeks or marketing approval, whichever is earlier
Other Pre-specified
Clinical Global Impression of Improvement (CGI-I)
The participant's overall clinical condition is compared to the one week period just before the start of medication (the baseline visit). The participant's condition is compared to the patient's condition at admission to the project \[prior to starting treatment\] on a 7-point scale, where 1=very much improved since the initiation of treatment; and 7=very much worse since the initiation of treatment. The CGI-I will be completed for all participants, regardless of chronological and developmental age.
Time frame: through study completion, up to 48 weeks or marketing approval, whichever is earlier
Other Pre-specified
Clinical Global Impression of Severity (CGI-S)
The severity of the participant's illness is rated on a seven-point scale, where 1=normal, not at all ill, and 7=among the most extremely ill patients. This rating is based upon observed and reported symptoms, behavior, and function in the past seven days. The score reflects the average severity level across the seven days. The CGI-S will be completed for all participants, regardless of chronological and developmental age.
Time frame: through study completion, up to 48 weeks or marketing approval, whichever is earlier
Other Pre-specified
Impact of Pediatric Epilepsy Scale (IPES)
The IPES assesses the impact on academic achievement, participation in activities, health, relationships with family and with peers and siblings, social activities, self-esteem, and the caregiver's hopes for their child's future. It takes about 3 minutes for the parent to complete. Each of the 11 items is given a severity score of 0 (not at all) to 3 (a lot). The higher the score, the higher is the impact of epilepsy on that item. The highest total score possible is 33 (range 0-33). The Impact of Pediatric Epilepsy Scale (IPES) is validated for subjects who are 2 to 16 years of age. Due to developmental delay characteristic of the study population, subjects through 18 years of chronological age will complete the IPES. Subjects over 18 years of chronological age will not complete the IPES.
Time frame: through study completion, up to 48 weeks or marketing approval, whichever is earlier