Infantile Spasms
Conditions
Keywords
infantile spasms, anticonvulsant, pediatric epilepsy, West Syndrome, epileptic spasms
Brief summary
To allow open-label extension to patients who have completed Protocol 1042-0500
Detailed description
Patient should have completed all scheduled clinical study visits in the double blind, controlled trial (Protocol 1042-0500) and have been deemed eligible (had a response to treatment) by the Investigator. Male or female, with a diagnosis of IS with a video EEG (vEEG) recording confirming the diagnosis. There will be a total of 14 visits over 99(+or-1)week. A 24-hr vEEG is only required if the subject has been spasm-free for more than 24-hrs.
Interventions
DRUGGanaxolone
Sponsors
Marinus Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Months to 24 Months
Healthy volunteers
No
Inclusion criteria
* Have completed all scheduled clinical study visits in the previous Protocol 1042 0500 and have been deemed eligible (no SAEs thought to be drug related and had a response to treatment) by the Investigator. * Be diagnosed with IS regardless of etiology. 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 24 hour 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 AEDs or fewer. * Have a parent/guardian who is properly informed of the nature and potential risks and benefits of the clinical study, is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study.
Exclusion criteria
* Current treatment with more than 2 concomitant AEDs. * 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 MRI. * Have any disease or condition (medical or surgical) at Screening that might compromise the hematologic, cardiovascular, pulmonary, renal, GI, 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 transaminase (AST), alanine transaminase (ALT), or total bilirubin greater than 4 times the upper limit of laboratory normal or any 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 enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Were Free of Spasms | Weeks 4 through Week 96 | Clinical spasms were determined by video-electroencephalography (VEEG). The number of participants with spasm-free duration have been presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Frequency of Individual Spasm | Baseline and Week 4 through Week 32 | Individual Spasm are seizures that may last only a second or two and were determined by a 24-hour video-electroencephalography (vEEG). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment prior to ganaxolone dosing in Protocol 1042-0500. |
| Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Week 4 through Week 32 | 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. |
| Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Week 4 through Week 32 | 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. |
| Change From Baseline in Frequency of Spasm Clusters | Baseline and Week 4 through Week 32 | Infantile spasms that come one after another in a cluster and lasts several minutes are called Spasm Clusters. Spasm clusters were determined by a 24-hour video-electroencephalography (vEEG). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment prior to ganaxolone dosing in Protocol 1042-0500. |
| Number of Participants With Absence of Spasms | Week 4 through Week 32 | Absence of spasms is defined as percentage of total spasm-free days during a visit period=100%. Parents/Guardians or nursing staff maintained a spasm/seizure diary to record the number and type of seizures each day, including spasms, throughout the entire study. The participants achieving absence of spasms have been presented. |
| Developmental Assessment Using Denver-II Developmental Test | Week 8 through Week 32 | 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. |
| Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Weeks 4 through Week 32 | Percentage of total spasm-free days during a visit period is defined as total number of spasm free days as recorded in the Seizure Diary/ total number of days during that period, multiplied by 100. Percentage of cumulative total spasm-free days during a visit period is defined as sum of total number of spasm-free days during this period as recorded in the Seizure Diary/ total number of days in the treatment period, multiplied by 100. |
| Number of Participants With Spasm-free Durations | Week 4 through Week 32 | Spasm-free duration is defined as total number of spasm-free days recorded in the spasm/seizure diary. Parents/Guardians or nursing staff maintained a spasm/seizure diary to record the number and type of seizures each day, including spasms, throughout the entire study. The number of participants with spasm-free duration of at least 24 hours have been presented. |
Countries
United States
Participant flow
Pre-assignment details
Participants who completed the previous double-blind controlled trial (Protocol 1042-0500, NCT00441896) were enrolled in this study. No separate analysis was performed to report results by doses.
Participants by arm
| Arm | Count |
|---|---|
| Ganaxolone Participants were administered a maximum dose of 54 mg/kg/day ganaxolone oral suspension. The investigator could adjust (increase or decrease) the dose of ganaxolone by 3 mg/kg t.i.d. (total daily dose adjustment = 9 mg/kg) until the optimal dose for efficacy and tolerability was achieved. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 2 |
| Overall Study | Discretion of the Investigator/Sponsor | 1 |
| Overall Study | Insufficient Clinical Response | 10 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Other | 21 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Ganaxolone |
|---|---|
| Age, Continuous | 13.4 months STANDARD_DEVIATION 6.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 54 |
| other Total, other adverse events | 47 / 54 |
| serious Total, serious adverse events | 24 / 54 |
Outcome results
Primary
Percentage of Participants Who Were Free of Spasms
Clinical spasms were determined by video-electroencephalography (VEEG). The number of participants with spasm-free duration have been presented.
Time frame: Weeks 4 through Week 96
Population: ITT Population included all participants who received at least 1 dose of open-label study medication. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ganaxolone | Percentage of Participants Who Were Free of Spasms | 100 percentage of participants |
Secondary
Change From Baseline in Frequency of Individual Spasm
Individual Spasm are seizures that may last only a second or two and were determined by a 24-hour video-electroencephalography (vEEG). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment prior to ganaxolone dosing in Protocol 1042-0500.
Time frame: Baseline and Week 4 through Week 32
Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ganaxolone | Change From Baseline in Frequency of Individual Spasm | Individual Spasms - Week 14 | -20.8 Individual spasms per day | Standard Deviation 31.21 |
| Ganaxolone | Change From Baseline in Frequency of Individual Spasm | Individual Spasms - Week 20 | -15.8 Individual spasms per day | Standard Deviation 52.46 |
| Ganaxolone | Change From Baseline in Frequency of Individual Spasm | Individual Spasms - Week 26 | -19.9 Individual spasms per day | Standard Deviation 39.27 |
| Ganaxolone | Change From Baseline in Frequency of Individual Spasm | Individual Spasms - Week 4 | -6.8 Individual spasms per day | Standard Deviation 40.7 |
| Ganaxolone | Change From Baseline in Frequency of Individual Spasm | Individual Spasms - Week 8 | -17.4 Individual spasms per day | Standard Deviation 31.28 |
| Ganaxolone | Change From Baseline in Frequency of Individual Spasm | Individual Spasms - Week 32 | -17.7 Individual spasms per day | Standard Deviation 36.35 |
Secondary
Change From Baseline in Frequency of Spasm Clusters
Infantile spasms that come one after another in a cluster and lasts several minutes are called Spasm Clusters. Spasm clusters were determined by a 24-hour video-electroencephalography (vEEG). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment prior to ganaxolone dosing in Protocol 1042-0500.
Time frame: Baseline and Week 4 through Week 32
Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ganaxolone | Change From Baseline in Frequency of Spasm Clusters | Spasm Clusters - Week 4 | -2.9 Spasm clusters per day | Standard Deviation 7.94 |
| Ganaxolone | Change From Baseline in Frequency of Spasm Clusters | Spasm Clusters - Week 14 | -4.1 Spasm clusters per day | Standard Deviation 9.12 |
| Ganaxolone | Change From Baseline in Frequency of Spasm Clusters | Spasm Clusters - Week 20 | -5.8 Spasm clusters per day | Standard Deviation 8.58 |
| Ganaxolone | Change From Baseline in Frequency of Spasm Clusters | Spasm Clusters - Week 8 | -4.1 Spasm clusters per day | Standard Deviation 8.35 |
| Ganaxolone | Change From Baseline in Frequency of Spasm Clusters | Spasm Clusters - Week 26 | -5.6 Spasm clusters per day | Standard Deviation 7.98 |
| Ganaxolone | Change From Baseline in Frequency of Spasm Clusters | Spasm Clusters - Week 32 | -5.3 Spasm clusters per day | Standard Deviation 9.96 |
Secondary
Developmental Assessment Using Denver-II Developmental Test
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: Week 8 through Week 32
Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 20- Personal Social | -2.82 Scores on a scale | Standard Deviation 6.081 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 8 - Personal Social | -0.72 Scores on a scale | Standard Deviation 3.899 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 8 - Fine Motor-Adaptive | -1.56 Scores on a scale | Standard Deviation 3.131 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 8 - Language | -1.45 Scores on a scale | Standard Deviation 2.798 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 8 - Gross Motor | -1.05 Scores on a scale | Standard Deviation 2.285 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 20- Fine Motor-Adaptive | -3.73 Scores on a scale | Standard Deviation 5.123 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 20- Language | -2.39 Scores on a scale | Standard Deviation 5.615 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 20 - Gross Motor | -2.69 Scores on a scale | Standard Deviation 3.584 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 32-Personal Social | -4.86 Scores on a scale | Standard Deviation 5.659 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 32-Fine Motor-Adaptive | -6.80 Scores on a scale | Standard Deviation 4.952 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 32-Language | -6.58 Scores on a scale | Standard Deviation 4.336 |
| Ganaxolone | Developmental Assessment Using Denver-II Developmental Test | Week 32-Gross Motor | -6.13 Scores on a scale | Standard Deviation 4.509 |
Secondary
Number of Participants With Absence of Spasms
Absence of spasms is defined as percentage of total spasm-free days during a visit period=100%. Parents/Guardians or nursing staff maintained a spasm/seizure diary to record the number and type of seizures each day, including spasms, throughout the entire study. The participants achieving absence of spasms have been presented.
Time frame: Week 4 through Week 32
Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ganaxolone | Number of Participants With Absence of Spasms | Achieved absence of spasms at Week 4 | 2 Participants |
| Ganaxolone | Number of Participants With Absence of Spasms | Achieved absence of spasms at Week 8 | 3 Participants |
| Ganaxolone | Number of Participants With Absence of Spasms | Achieved absence of spasms at Week 14 | 3 Participants |
| Ganaxolone | Number of Participants With Absence of Spasms | Achieved absence of spasms at Week 20 | 4 Participants |
| Ganaxolone | Number of Participants With Absence of Spasms | Achieved absence of spasms at Week 26 | 5 Participants |
| Ganaxolone | Number of Participants With Absence of Spasms | Achieved absence of spasms at Week 32 | 1 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: Week 4 through Week 32
Population: ITT population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's -Week 4 - Slight Improvement | 16 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's- Week 4 - No change from Baseline | 6 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 4 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 8 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's- Week 4 - Marked Improvement | 11 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 4 - Moderate Improvement | 11 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 4 - Slight Worsening | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 4 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 8 - Marked Improvement | 7 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's- Week 8 - Moderate Improvement | 12 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's -Week 8 - Slight Improvement | 18 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's- Week 8 - No change from Baseline | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 8 - Slight Worsening | 2 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 8 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's- Week 14 - Marked Improvement | 8 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 14 - Moderate Improvement | 13 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's -Week 14 - Slight Improvement | 14 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 14 - No change from Baseline | 2 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 14 - Slight Worsening | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 14 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 14 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 20 - Marked Improvement | 9 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 20 - Moderate Improvement | 13 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's -Week 20 - Slight Improvement | 10 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's- Week 20 - No change from Baseline | 3 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's- Week 20 - Slight Worsening | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 20 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 20 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's- Week 26 - Marked Improvement | 9 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's- Week 26 - Moderate Improvement | 12 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's -Week 26 - Slight Improvement | 7 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 26 - No change from Baseline | 3 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 26 - Slight Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 26 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 26 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 32 - Marked Improvement | 8 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 32 - Moderate Improvement | 7 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's-Week 32 - Slight Improvement | 8 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 32 - No change from Baseline | 2 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 32 - Slight Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 32 - Moderate Worsening | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment | Caregiver's - Week 32 - Marked Worsening | 0 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: Week 4 through Week 32
Population: ITT population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's- Week 4 - Marked Improvement | 7 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 4 - Moderate Improvement | 15 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 4 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 8 - Marked Improvement | 6 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's- Week 8 - Moderate Improvement | 12 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's -Week 8 - Slight Improvement | 19 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 14 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 20 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 20 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's- Week 26 - Marked Improvement | 5 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 26 - No change from Baseline | 4 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 26 - Slight Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's -Week 4 - Slight Improvement | 18 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's- Week 4 - No change from Baseline | 4 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 4 - Moderate Worsening | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 4 - Slight Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's- Week 8 - No change from Baseline | 3 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 8 - Slight Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 8 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 8 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's- Week 14 - Marked Improvement | 6 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 14 - Moderate Improvement | 16 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's -Week 14 - Slight Improvement | 15 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 14 - No change from Baseline | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 14 - Slight Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 14 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 20 - Marked Improvement | 7 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 20 - Moderate Improvement | 14 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's -Week 20 - Slight Improvement | 11 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's- Week 20 - No change from Baseline | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's- Week 20 - Slight Worsening | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's- Week 26 - Moderate Improvement | 14 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's -Week 26 - Slight Improvement | 9 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 26 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 26 - Marked Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 32 - Marked Improvement | 6 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 32 - Moderate Improvement | 9 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's -Week 32 - Slight Improvement | 8 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 32 - No change from Baseline | 3 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 32 - Slight Worsening | 1 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 32 - Moderate Worsening | 0 participants |
| Ganaxolone | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment | Investigator's - Week 32 - Marked Worsening | 0 participants |
Secondary
Number of Participants With Spasm-free Durations
Spasm-free duration is defined as total number of spasm-free days recorded in the spasm/seizure diary. Parents/Guardians or nursing staff maintained a spasm/seizure diary to record the number and type of seizures each day, including spasms, throughout the entire study. The number of participants with spasm-free duration of at least 24 hours have been presented.
Time frame: Week 4 through Week 32
Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ganaxolone | Number of Participants With Spasm-free Durations | Spasm Free at Week 4 | 19 Participants |
| Ganaxolone | Number of Participants With Spasm-free Durations | Spasm Free at Week 8 | 18 Participants |
| Ganaxolone | Number of Participants With Spasm-free Durations | Spasm Free at Week 14 | 18 Participants |
| Ganaxolone | Number of Participants With Spasm-free Durations | Spasm Free at Week 20 | 18 Participants |
| Ganaxolone | Number of Participants With Spasm-free Durations | Spasm Free at Week 26 | 17 Participants |
| Ganaxolone | Number of Participants With Spasm-free Durations | Spasm Free at Week 32 | 13 Participants |
Secondary
Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary.
Percentage of total spasm-free days during a visit period is defined as total number of spasm free days as recorded in the Seizure Diary/ total number of days during that period, multiplied by 100. Percentage of cumulative total spasm-free days during a visit period is defined as sum of total number of spasm-free days during this period as recorded in the Seizure Diary/ total number of days in the treatment period, multiplied by 100.
Time frame: Weeks 4 through Week 32
Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Total Spasm-free days during Week 4 visit | 11.10 Percentage of Days | Standard Deviation 23.657 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Total Spasm-free days during Week 8 visit | 18.74 Percentage of Days | Standard Deviation 32.654 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Total Spasm-free days during Week 14 visit | 20.74 Percentage of Days | Standard Deviation 34.817 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Total Spasm-free days during Week 20 visit | 28.79 Percentage of Days | Standard Deviation 40.163 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Total Spasm-free days during Week 26 visit | 28.73 Percentage of Days | Standard Deviation 39.711 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Total Spasm-free days during week 32 visit | 27.99 Percentage of Days | Standard Deviation 39.259 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Cumulative Spasm-free days during Week 4 visit | 10.86 Percentage of Days | Standard Deviation 20.374 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Cumulative Spasm-free days during Week 8 visit | 13.82 Percentage of Days | Standard Deviation 23.433 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Cumulative Spasm-free days during Week 14 visit | 15.70 Percentage of Days | Standard Deviation 25.769 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Cumulative Spasm-free days during Week 20 visit | 19.97 Percentage of Days | Standard Deviation 28.501 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Cumulative Spasm-free days during Week 26 visit | 22.07 Percentage of Days | Standard Deviation 31.105 |
| Ganaxolone | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. | Cumulative Spasm-free days during Week 32 visit | 22.99 Percentage of Days | Standard Deviation 30.14 |