Infantile Spasms
Conditions
Keywords
infantile spasms, anticonvulsant, pediatric epilepsy, West Syndrome, epileptic spasms
Brief summary
The study consists of cohorts where participants are randomized, in a 2:1 ratio, to 1 of 2 sequences, A and B. In each cohort, Sequence A, comprised of participants, who will receive ascending doses of ganaxolone and ascending doses of placebo. Sequence B, comprised of participants, who will receive ascending doses of placebo and ascending doses of ganaxolone. The dosing level in each subsequent cohort will be based upon experience gained from previous cohorts.
Detailed description
Male or female, 4 to 24 months of age (inclusive) with a diagnosis of IS with a 24 hour video EEG (vEEG) recording confirming the diagnosis and previously treated with 3 or fewer antiepileptic drugs (AEDs) are eligible for the study. The subject is able to continue treatment with concomitant AEDs (no more than 2; adrenocorticotropic hormone \[ACTH\], corticosteroids, felbamate, and vigabatrin are not allowed concomitantly). A ketogenic diet is permitted if it can be maintained for the duration of the study. There will be a total of three weekly 24-hr video EEGs (baseline, end of weeks 1 and 2 of treatment). Dosing titration begins the day after each video EEG during the inpatient stay. All subjects will be receiving ganaxolone the day after the second video EEG. A Data Monitoring Board (DMB) will determine whether successive cohorts of subjects can be dosed at an increased dose level; up to a maximum of 6 cohorts.
Interventions
DRUGGanaxolone
OTHERPlacebo
Sponsors
Marinus Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Months to 24 Months
Healthy volunteers
No
Inclusion criteria
* Be diagnosed with IS (regardless of etiology- except for a progressive neurologic illness). Diagnostic Criteria: Seizures consisting of single or repetitive short muscular contractions leading to flexion or extension. Spasms may be characterized as tonic or myoclonic contractions, may occur singly or in clusters, and typically occur bilaterally and symmetrically. The EEG pattern must be consistent with the diagnosis of IS (hypsarrhythmia, modified hypsarrhythmia, multifocal spike wave discharges, etc). * Have a vEEG recording confirming the diagnosis of IS. * Have had a magnetic resonance imaging (MRI) performed to determine any possible causes of IS. * Have been previously treated with 3 or fewer AEDs. * If being treated with concomitant AEDs * Current AEDs have been at a constant daily dose for at least 2 weeks; Note: Subjects with minor dose adjustments may be allowed to enter the study after shorter periods after detailed discussion with the medical monitor. * Have a stable clinical response/plateau for at least 2 weeks * Are able to continue treatment with no more than 2 concomitant AEDs (ACTH, corticosteroids, felbamate, and vigabatrin are not allowed concomitantly). * A ketogenic diet is permitted if it can be maintained for the duration of the study. * Be a male or female, 4 to 24 months of age (inclusive) * Have a Parent/Guardian who is properly informed of the nature and risks of the clinical study, who is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study * Be able to participate for the full term of the clinical study.
Exclusion criteria
* Treatment with corticosteroids, ACTH, vigabatrin, felbamate, or any AED not approved by Regulatory Agencies, 2 weeks prior to randomization. * Treatment with more than two AEDs at baseline. * Have an active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive (with the exception of tuberous sclerosis) as evaluated by brain imaging (MRI). * Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk. * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin greater than four times the upper limit of normal (ULN) or clinical laboratory value deemed clinically significant by the Investigator. * History of recurrent status epilepticus. * Have been exposed to any other investigational drug within 30 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Frequency of Spasm Clusters at Day 10 | Baseline (Day 0) and Day 10 | Spasm clusters were determined by a 24-hour video-electroencephalography (vEEG) at Day 10. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment before study drug infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Absence of Hypsarrhythmia | Day 10 and Day 20 | Absence of hypsarrhythmia was determined by 24-hour vEEG at Day 10 and Day 20. |
| Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Baseline (Day 0), Day 10 and Day 20 | The investigators rated the participants' overall clinical status based on 7 clinical factors: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale (\[1\] marked improvement, \[2\] moderate improvement, \[3\] slight improvement, \[4\] no change from Baseline, \[5\] slight worsening, \[6\] moderate worsening, or \[7\] marked worsening). Higher score indicated worse symptoms. The investigators assessed the participants' status compared to their condition prior to initiating study medication. |
| Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Baseline (Day 0), Day10 and Day 20 | Caregiver global assessment of seizure severity and response to treatment rated the participants' based on 7 clinical factors: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale (\[1\] marked improvement, \[2\] moderate improvement, \[3\] slight improvement, \[4\] no change from Baseline, \[5\] slight worsening, \[6\] moderate worsening, or \[7\] marked worsening). Higher score indicated worse symptoms. The assessment compared the participants' current status to their condition prior to initiating study medication. |
| Change From Baseline in Frequency of Spasm Clusters at Day 20 | Baseline (Day 0) and Day 20 | Spasm clusters were determined by a 24-hour vEEG at Day 20. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment before study drug infusion. |
| Number of Participants With Seizure-free Days | From Day 8 to Day 10 and From Day 18 to Day 20 | Seizure-free days were measured using data obtained from participants' daily dairy. Participants without seizures have been reported. |
| Number of Responders | Day 10 and Day 20 | A responder is defined as a participant experiencing a greater than equal to (\>=) 50 percent (%) decrease in spasm frequency. Test for responders was conducted by vEEG for up to 24 hours at Day 10 and Day 20 |
| Developmental Assessment Using Denver-II Developmental Test at Day 20 | At Day 20 | Denver-II Developmental Test measures a child's development in several areas:Personal-Social,Fine Motor-Adaptive,Language,and Gross Motor,from birth to 6 years old.It consists of 125 items that are organized into subscales and scored as pass,fail,or refused.To evaluate a child's progress,test compares their performance to a normative sample of children of same age.For each item,age at which 90% of children in normative sample pass it is determined.Derived score for each subscale is sum of item scores and represents difference between child's chronological age and age at which 90% of children in normative sample pass the items in that subscale.A higher derived score on a subscale indicates better performance on items in that subscale relative to other children of same age who have taken the test.Among subscales,Personal-Social subscale ranges from -16 months to 24 months;others range from - 12 months to 24 months.All subscales have a population mean of 0 and a standard deviation of 3. |
| Number of Participants With Spasm-free Durations | Day 10 and Day 20 | Clinical spasms were determined by vEEG for at least 24 hours at Day 10 and Day 20. The number of participants with spasm-free duration have been presented. |
Countries
United States
Participant flow
Recruitment details
This was a randomized, placebo-controlled, double-blind, dose-ranging study in which participants were randomized to ganaxolone:placebo in a 2:1 ratio into one of 5 cohorts. The primary focus of the study was to explore the dosing and titration schedule to help determine how rapidly infants can be titrated to a Maximum tolerated dose (MTD) to control spasms.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone Participants were administered oral suspension of ganaxolone followed by placebo and then ganaxolone using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 1 received starting doses of 3 mg/kg tid with maximum allowable doses of 36 mg/kg/day (12 mg/kg tid). | 6 |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo Participants were administered placebo followed by oral suspension of ganaxolone and then placebo using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 1 received starting doses of 3 mg/kg tid with maximum allowable doses of 36 mg/kg/day (12 mg/kg tid). | 3 |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone Participants were administered oral suspension of ganaxolone followed by placebo and then ganaxolone using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 2 received starting doses of 6 mg/kg tid with maximum allowable doses of 45 mg/kg/day (15 mg/kg tid). | 7 |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo Participants were administered placebo followed by oral suspension of ganaxolone and then placebo using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 2 received starting doses of 6 mg/kg tid with maximum allowable doses of 45 mg/kg/day (15 mg/kg tid). | 4 |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone Participants were administered oral suspension of ganaxolone followed by placebo and then ganaxolone using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 3 received starting doses of 9 mg/kg tid with maximum allowable doses of 54 mg/kg/day (18 mg/kg tid). | 11 |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo Participants were administered placebo followed by oral suspension of ganaxolone and then placebo using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 3 received starting doses of 9 mg/kg tid with maximum allowable doses of 54 mg/kg/day (18 mg/kg tid). | 3 |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone Participants were administered oral suspension of ganaxolone followed by placebo and then ganaxolone using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 4 received starting doses of 12 mg/kg tid with maximum allowable doses of 54 mg/kg/day (18 mg/kg tid). | 7 |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo Participants were administered placebo followed by oral suspension of ganaxolone and then placebo using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 4 received starting doses of 12 mg/kg tid with maximum allowable doses of 54 mg/kg/day (18 mg/kg tid). | 5 |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone Participants were administered oral suspension of ganaxolone followed by placebo and then ganaxolone using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 5 received starting doses of 18 mg/kg tid with maximum allowable doses of 54 mg/kg/day (18 mg/kg tid). | 6 |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo Participants were administered placebo followed by oral suspension of ganaxolone and then placebo using an oral dosing syringe by hospital staff/parents/guardians tid. Each dose was separated by a minimum of 4 hours and a maximum of 8 hours. Participants in Cohort 5 received starting doses of 18 mg/kg tid with maximum allowable doses of 54 mg/kg/day (18 mg/kg tid). | 4 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Other | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 8.2 Months STANDARD_DEVIATION 2.48 | 20.3 Months STANDARD_DEVIATION 3.06 | 13.4 Months STANDARD_DEVIATION 4.89 | 23.0 Months STANDARD_DEVIATION 12.25 | 11.2 Months STANDARD_DEVIATION 5.47 | 14.0 Months STANDARD_DEVIATION 6.93 | 10.3 Months STANDARD_DEVIATION 4.96 | 13.2 Months STANDARD_DEVIATION 3.03 | 11.3 Months STANDARD_DEVIATION 3.27 | 11.5 Months STANDARD_DEVIATION 7.55 | 12.7 Months STANDARD_DEVIATION 6.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 10 Participants | 1 Participants | 5 Participants | 4 Participants | 6 Participants | 4 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 7 Participants | 1 Participants | 6 Participants | 3 Participants | 5 Participants | 3 Participants | 1 Participants | 3 Participants | 34 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 5 Participants | 1 Participants | 6 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 32 Participants |
| Sex: Female, Male Male | 3 Participants | 0 Participants | 2 Participants | 3 Participants | 5 Participants | 1 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 7 | 0 / 4 | 0 / 11 | 0 / 3 | 0 / 7 | 0 / 5 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 6 / 6 | 3 / 3 | 5 / 7 | 1 / 4 | 9 / 11 | 1 / 3 | 4 / 7 | 2 / 5 | 4 / 6 | 4 / 4 |
| serious Total, serious adverse events | 2 / 6 | 0 / 3 | 0 / 7 | 0 / 4 | 0 / 11 | 0 / 3 | 2 / 7 | 0 / 5 | 0 / 6 | 0 / 4 |
Outcome results
Primary
Change From Baseline in Frequency of Spasm Clusters at Day 10
Spasm clusters were determined by a 24-hour video-electroencephalography (vEEG) at Day 10. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment before study drug infusion.
Time frame: Baseline (Day 0) and Day 10
Population: Efficacy Population included all randomized participants who received at least 1 evaluation of efficacy at both Baseline (Day 0) and at either Visit 5 (Day 10) or Visit 8 (Day 20). Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 10 | 1.0 Spasm clusters per day | Standard Deviation 20.06 |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 10 | 2.7 Spasm clusters per day | Standard Deviation 6.66 |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 10 | -5.4 Spasm clusters per day | Standard Deviation 10.97 |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 10 | -1.0 Spasm clusters per day | Standard Deviation 1.83 |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 10 | -1.4 Spasm clusters per day | Standard Deviation 13.69 |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 10 | -5.3 Spasm clusters per day | Standard Deviation 10.12 |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 10 | -3.7 Spasm clusters per day | Standard Deviation 4.92 |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 10 | 0.2 Spasm clusters per day | Standard Deviation 13.12 |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 10 | -3.2 Spasm clusters per day | Standard Deviation 5.02 |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 10 | -1.7 Spasm clusters per day | Standard Deviation 7.64 |
p-value: 0.7391ANCOVA
p-value: 0.537ANCOVA
p-value: 0.908ANCOVA
p-value: 0.2539ANCOVA
p-value: 0.6657ANCOVA
Secondary
Change From Baseline in Frequency of Spasm Clusters at Day 20
Spasm clusters were determined by a 24-hour vEEG at Day 20. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment before study drug infusion.
Time frame: Baseline (Day 0) and Day 20
Population: Efficacy Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 20 | -3.2 Spasm clusters per day | Standard Deviation 10.91 |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 20 | 6.0 Spasm clusters per day | Standard Deviation 11.53 |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 20 | -5.0 Spasm clusters per day | Standard Deviation 7.55 |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 20 | -1.5 Spasm clusters per day | Standard Deviation 3.11 |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 20 | -1.1 Spasm clusters per day | Standard Deviation 11.21 |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 20 | -12.7 Spasm clusters per day | Standard Deviation 26.27 |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 20 | -4.4 Spasm clusters per day | Standard Deviation 6.63 |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 20 | -1.2 Spasm clusters per day | Standard Deviation 13.85 |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Change From Baseline in Frequency of Spasm Clusters at Day 20 | -3.2 Spasm clusters per day | Standard Deviation 4.92 |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Change From Baseline in Frequency of Spasm Clusters at Day 20 | -5.3 Spasm clusters per day | Standard Deviation 7.57 |
p-value: 0.4249ANCOVA
p-value: 0.4177ANCOVA
p-value: 0.3033ANCOVA
p-value: 0.3014ANCOVA
p-value: 0.1839ANCOVA
Secondary
Developmental Assessment Using Denver-II Developmental Test at Day 20
Denver-II Developmental Test measures a child's development in several areas:Personal-Social,Fine Motor-Adaptive,Language,and Gross Motor,from birth to 6 years old.It consists of 125 items that are organized into subscales and scored as pass,fail,or refused.To evaluate a child's progress,test compares their performance to a normative sample of children of same age.For each item,age at which 90% of children in normative sample pass it is determined.Derived score for each subscale is sum of item scores and represents difference between child's chronological age and age at which 90% of children in normative sample pass the items in that subscale.A higher derived score on a subscale indicates better performance on items in that subscale relative to other children of same age who have taken the test.Among subscales,Personal-Social subscale ranges from -16 months to 24 months;others range from - 12 months to 24 months.All subscales have a population mean of 0 and a standard deviation of 3.
Time frame: At Day 20
Population: Efficacy Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -4.38 Scores on a scale | Standard Deviation 1.834 |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -1.36 Scores on a scale | Standard Deviation 2.681 |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -3.96 Scores on a scale | Standard Deviation 2.532 |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -5.48 Scores on a scale | Standard Deviation 1.618 |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -14.63 Scores on a scale | Standard Deviation 2.409 |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -12.33 Scores on a scale | Standard Deviation 4.196 |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -16.90 Scores on a scale | Standard Deviation 2.563 |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -13.63 Scores on a scale | Standard Deviation 2.079 |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -7.49 Scores on a scale | Standard Deviation 5.414 |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -8.79 Scores on a scale | Standard Deviation 5.874 |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -7.23 Scores on a scale | Standard Deviation 7.02 |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -7.16 Scores on a scale | Standard Deviation 5.298 |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -7.00 Scores on a scale | Standard Deviation 5.828 |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -5.17 Scores on a scale | Standard Deviation 3.017 |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -8.73 Scores on a scale | Standard Deviation 6.071 |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -7.70 Scores on a scale | Standard Deviation 5.624 |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -7.76 Scores on a scale | Standard Deviation 3.727 |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -6.40 Scores on a scale | Standard Deviation 4.224 |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -5.58 Scores on a scale | Standard Deviation 3.329 |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -5.82 Scores on a scale | Standard Deviation 3.88 |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -4.95 Scores on a scale | Standard Deviation 0.778 |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -3.00 Scores on a scale | Standard Deviation 2.546 |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -5.05 Scores on a scale | Standard Deviation 2.051 |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -5.35 Scores on a scale | Standard Deviation 0.354 |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -6.09 Scores on a scale | Standard Deviation 4.674 |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -6.16 Scores on a scale | Standard Deviation 4.484 |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -5.99 Scores on a scale | Standard Deviation 4.354 |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -6.89 Scores on a scale | Standard Deviation 4.282 |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -10.24 Scores on a scale | Standard Deviation 6.08 |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -10.22 Scores on a scale | Standard Deviation 4.925 |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -8.22 Scores on a scale | Standard Deviation 5.644 |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -8.74 Scores on a scale | Standard Deviation 5.546 |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -7.72 Scores on a scale | Standard Deviation 4.581 |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -8.76 Scores on a scale | Standard Deviation 3.26 |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -8.32 Scores on a scale | Standard Deviation 3.637 |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -7.44 Scores on a scale | Standard Deviation 3.089 |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Language at Day 20 | -10.77 Scores on a scale | Standard Deviation 7.223 |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Personal Social at Day 20 | -12.93 Scores on a scale | Standard Deviation 7.336 |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Fine Motor Adaptive at Day 20 | -12.87 Scores on a scale | Standard Deviation 7.731 |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Developmental Assessment Using Denver-II Developmental Test at Day 20 | Gross Motor at Day 20 | -13.43 Scores on a scale | Standard Deviation 8.618 |
Secondary
Number of Participants With Absence of Hypsarrhythmia
Absence of hypsarrhythmia was determined by 24-hour vEEG at Day 10 and Day 20.
Time frame: Day 10 and Day 20
Population: Efficacy Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 1 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 1 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 2 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 2 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 2 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 2 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 2 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 2 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 2 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 2 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 1 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 3 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Absence of Hypsarrhythmia | Day 20 | 0 Participants |
Secondary
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver global assessment of seizure severity and response to treatment rated the participants' based on 7 clinical factors: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale (\[1\] marked improvement, \[2\] moderate improvement, \[3\] slight improvement, \[4\] no change from Baseline, \[5\] slight worsening, \[6\] moderate worsening, or \[7\] marked worsening). Higher score indicated worse symptoms. The assessment compared the participants' current status to their condition prior to initiating study medication.
Time frame: Baseline (Day 0), Day10 and Day 20
Population: Efficacy population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 2 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 4 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 1 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 1 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 1 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 2 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 2 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 1 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 2 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 1 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 2 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 3 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 1 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 4 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 1 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 2 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 2 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 2 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 1 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 2 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 6 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 5 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 4 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 1 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 2 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 1 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 1 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 2 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 2 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 2 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 3 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 1 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 2 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 3 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 2 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 1 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 1 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 3 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 3 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 2 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 2 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 3 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 1 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 1 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 4 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 10 | 2 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Slight improvement at Day 10 | 1 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | No change from Baseline at Day 20 | 3 Participants |
Secondary
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
The investigators rated the participants' overall clinical status based on 7 clinical factors: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale (\[1\] marked improvement, \[2\] moderate improvement, \[3\] slight improvement, \[4\] no change from Baseline, \[5\] slight worsening, \[6\] moderate worsening, or \[7\] marked worsening). Higher score indicated worse symptoms. The investigators assessed the participants' status compared to their condition prior to initiating study medication.
Time frame: Baseline (Day 0), Day 10 and Day 20
Population: Efficacy Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 1 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 1 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 1 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 2 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 2 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 4 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 3 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 2 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 1 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 1 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 2 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 2 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 3 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 4 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 1 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 1 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 3 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 1 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 2 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 2 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 1 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 2 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 7 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 6 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 1 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 1 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 3 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 2 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 2 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 1 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 2 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 2 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 3 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 4 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 1 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 3 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 3 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 2 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 3 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 2 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 4 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 1 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 1 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 10 | 3 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight improvement at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | No change from Baseline at Day 20 | 2 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Slight worsening at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 10 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Marked improvement at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Severe worsening at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Moderate improvement at Day 20 | 1 Participants |
Secondary
Number of Participants With Seizure-free Days
Seizure-free days were measured using data obtained from participants' daily dairy. Participants without seizures have been reported.
Time frame: From Day 8 to Day 10 and From Day 18 to Day 20
Population: Efficacy Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 6 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 6 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 1 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 2 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 6 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 6 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 4 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 3 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 10 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 10 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 3 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 3 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 6 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 6 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 5 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 5 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 6 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 6 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 18 to Day 20 | 3 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Seizure-free Days | From Day 8 to Day 10 | 3 Participants |
Secondary
Number of Participants With Spasm-free Durations
Clinical spasms were determined by vEEG for at least 24 hours at Day 10 and Day 20. The number of participants with spasm-free duration have been presented.
Time frame: Day 10 and Day 20
Population: Efficacy Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 3 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 3 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 1 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 1 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 2 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 3 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 2 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 2 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 2 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 2 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 1 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 0 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 3 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 1 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 0 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 1 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 1 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 20 | 0 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Participants With Spasm-free Durations | Spasm-free Durations at Day 10 | 0 Participants |
Secondary
Number of Responders
A responder is defined as a participant experiencing a greater than equal to (\>=) 50 percent (%) decrease in spasm frequency. Test for responders was conducted by vEEG for up to 24 hours at Day 10 and Day 20
Time frame: Day 10 and Day 20
Population: Efficacy Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 20 | 2 Participants |
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 10 | 2 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 20 | 0 Participants |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 10 | 1 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 20 | 4 Participants |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 10 | 3 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 20 | 2 Participants |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 10 | 0 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 10 | 3 Participants |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 20 | 3 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 10 | 0 Participants |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 20 | 1 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 10 | 2 Participants |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 20 | 4 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 20 | 1 Participants |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 10 | 2 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 10 | 2 Participants |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | Number of Responders | Day 20 | 1 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 20 | 1 Participants |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | Number of Responders | Day 10 | 1 Participants |