Trial Outcomes & Findings for Open-label Extension to Protocol 1042-0500 (NCT NCT00442104)
NCT ID: NCT00442104
Last Updated: 2024-05-28
Results Overview
Clinical spasms were determined by video-electroencephalography (VEEG). The number of participants with spasm-free duration have been presented.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
54 participants
Primary outcome timeframe
Weeks 4 through Week 96
Results posted on
2024-05-28
Participant Flow
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.
Participant milestones
| Measure |
Ganaxolone
Participants were administered a maximum dose of 54 milligrams per kilogram (mg/kg)/day ganaxolone oral suspension. The investigator could adjust (increase or decrease) the dose of ganaxolone by 3 mg/kg three times a day (total daily dose adjustment = 9 mg/kg) until the optimal dose for efficacy and tolerability was achieved
|
|---|---|
|
Overall Study
STARTED
|
54
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
47
|
Reasons for withdrawal
| Measure |
Ganaxolone
Participants were administered a maximum dose of 54 milligrams per kilogram (mg/kg)/day ganaxolone oral suspension. The investigator could adjust (increase or decrease) the dose of ganaxolone by 3 mg/kg three times a day (total daily dose adjustment = 9 mg/kg) until the optimal dose for efficacy and tolerability was achieved
|
|---|---|
|
Overall Study
Adverse Event
|
5
|
|
Overall Study
Death
|
2
|
|
Overall Study
Lost to Follow-up
|
3
|
|
Overall Study
Withdrawal by Subject
|
5
|
|
Overall Study
Insufficient Clinical Response
|
10
|
|
Overall Study
Other
|
21
|
|
Overall Study
Discretion of the Investigator/Sponsor
|
1
|
Baseline Characteristics
Open-label Extension to Protocol 1042-0500
Baseline characteristics by cohort
| Measure |
Ganaxolone
n=54 Participants
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.
|
|---|---|
|
Age, Continuous
|
13.4 months
STANDARD_DEVIATION 6.38 • n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
47 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
33 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Weeks 4 through Week 96Population: 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.
Clinical spasms were determined by video-electroencephalography (VEEG). The number of participants with spasm-free duration have been presented.
Outcome measures
| Measure |
Ganaxolone
n=7 Participants
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.
|
|---|---|
|
Percentage of Participants Who Were Free of Spasms
|
100 percentage of participants
Interval 59.0 to 100.0
|
SECONDARY outcome
Timeframe: Baseline and Week 4 through Week 32Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
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.
Outcome measures
| Measure |
Ganaxolone
n=40 Participants
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.
|
|---|---|
|
Change From Baseline in Frequency of Spasm Clusters
Spasm Clusters - Week 4
|
-2.9 Spasm clusters per day
Standard Deviation 7.94
|
|
Change From Baseline in Frequency of Spasm Clusters
Spasm Clusters - Week 8
|
-4.1 Spasm clusters per day
Standard Deviation 8.35
|
|
Change From Baseline in Frequency of Spasm Clusters
Spasm Clusters - Week 14
|
-4.1 Spasm clusters per day
Standard Deviation 9.12
|
|
Change From Baseline in Frequency of Spasm Clusters
Spasm Clusters - Week 20
|
-5.8 Spasm clusters per day
Standard Deviation 8.58
|
|
Change From Baseline in Frequency of Spasm Clusters
Spasm Clusters - Week 26
|
-5.6 Spasm clusters per day
Standard Deviation 7.98
|
|
Change From Baseline in Frequency of Spasm Clusters
Spasm Clusters - Week 32
|
-5.3 Spasm clusters per day
Standard Deviation 9.96
|
SECONDARY outcome
Timeframe: Baseline and Week 4 through Week 32Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
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.
Outcome measures
| Measure |
Ganaxolone
n=39 Participants
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.
|
|---|---|
|
Change From Baseline in Frequency of Individual Spasm
Individual Spasms - Week 14
|
-20.8 Individual spasms per day
Standard Deviation 31.21
|
|
Change From Baseline in Frequency of Individual Spasm
Individual Spasms - Week 32
|
-17.7 Individual spasms per day
Standard Deviation 36.35
|
|
Change From Baseline in Frequency of Individual Spasm
Individual Spasms - Week 4
|
-6.8 Individual spasms per day
Standard Deviation 40.70
|
|
Change From Baseline in Frequency of Individual Spasm
Individual Spasms - Week 8
|
-17.4 Individual spasms per day
Standard Deviation 31.28
|
|
Change From Baseline in Frequency of Individual Spasm
Individual Spasms - Week 20
|
-15.8 Individual spasms per day
Standard Deviation 52.46
|
|
Change From Baseline in Frequency of Individual Spasm
Individual Spasms - Week 26
|
-19.9 Individual spasms per day
Standard Deviation 39.27
|
SECONDARY outcome
Timeframe: Week 4 through Week 32Population: ITT population. Only those participants with data available at the indicated time point were analyzed.
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.
Outcome measures
| Measure |
Ganaxolone
n=45 Participants
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.
|
|---|---|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's- Week 4 - Marked Improvement
|
11 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 4 - Moderate Improvement
|
11 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's -Week 4 - Slight Improvement
|
16 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's- Week 4 - No change from Baseline
|
6 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 4 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 4 - Slight Worsening
|
1 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 4 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 8 - Marked Improvement
|
7 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's- Week 8 - Moderate Improvement
|
12 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's -Week 8 - Slight Improvement
|
18 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's- Week 8 - No change from Baseline
|
1 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 8 - Slight Worsening
|
2 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 8 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 8 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's- Week 14 - Marked Improvement
|
8 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 14 - Moderate Improvement
|
13 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's -Week 14 - Slight Improvement
|
14 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 14 - No change from Baseline
|
2 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 14 - Slight Worsening
|
1 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 14 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 14 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 20 - Marked Improvement
|
9 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 20 - Moderate Improvement
|
13 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's -Week 20 - Slight Improvement
|
10 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's- Week 20 - No change from Baseline
|
3 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's- Week 20 - Slight Worsening
|
1 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 20 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 20 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's- Week 26 - Marked Improvement
|
9 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's- Week 26 - Moderate Improvement
|
12 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's -Week 26 - Slight Improvement
|
7 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 26 - No change from Baseline
|
3 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 26 - Slight Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 26 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 26 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 32 - Marked Improvement
|
8 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 32 - Moderate Improvement
|
7 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's-Week 32 - Slight Improvement
|
8 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 32 - No change from Baseline
|
2 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 32 - Slight Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 32 - Moderate Worsening
|
1 participants
|
|
Number of Participants With Change in Clinical Status on Caregiver's Global Assessment
Caregiver's - Week 32 - Marked Worsening
|
0 participants
|
SECONDARY outcome
Timeframe: Week 4 through Week 32Population: ITT population. Only those participants with data available at the indicated time point were analyzed.
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.
Outcome measures
| Measure |
Ganaxolone
n=45 Participants
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.
|
|---|---|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's- Week 4 - Marked Improvement
|
7 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 4 - Moderate Improvement
|
15 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's -Week 4 - Slight Improvement
|
18 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's- Week 4 - No change from Baseline
|
4 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 4 - Moderate Worsening
|
1 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 4 - Slight Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 4 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 8 - Marked Improvement
|
6 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's- Week 8 - Moderate Improvement
|
12 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's -Week 8 - Slight Improvement
|
19 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's- Week 8 - No change from Baseline
|
3 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 8 - Slight Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 8 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 8 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's- Week 14 - Marked Improvement
|
6 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 14 - Moderate Improvement
|
16 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's -Week 14 - Slight Improvement
|
15 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 14 - No change from Baseline
|
1 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 14 - Slight Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 14 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 14 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 20 - Marked Improvement
|
7 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 20 - Moderate Improvement
|
14 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's -Week 20 - Slight Improvement
|
11 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's- Week 20 - No change from Baseline
|
1 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's- Week 20 - Slight Worsening
|
1 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 20 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 20 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's- Week 26 - Marked Improvement
|
5 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's- Week 26 - Moderate Improvement
|
14 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's -Week 26 - Slight Improvement
|
9 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 26 - No change from Baseline
|
4 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 26 - Slight Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 26 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 26 - Marked Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 32 - Marked Improvement
|
6 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 32 - Moderate Improvement
|
9 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's -Week 32 - Slight Improvement
|
8 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 32 - No change from Baseline
|
3 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 32 - Slight Worsening
|
1 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 32 - Moderate Worsening
|
0 participants
|
|
Number of Participants With Change in Clinical Status on the Investigator's Global Assessment
Investigator's - Week 32 - Marked Worsening
|
0 participants
|
SECONDARY outcome
Timeframe: Week 4 through Week 32Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
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.
Outcome measures
| Measure |
Ganaxolone
n=43 Participants
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.
|
|---|---|
|
Number of Participants With Spasm-free Durations
Spasm Free at Week 4
|
19 Participants
|
|
Number of Participants With Spasm-free Durations
Spasm Free at Week 8
|
18 Participants
|
|
Number of Participants With Spasm-free Durations
Spasm Free at Week 14
|
18 Participants
|
|
Number of Participants With Spasm-free Durations
Spasm Free at Week 20
|
18 Participants
|
|
Number of Participants With Spasm-free Durations
Spasm Free at Week 26
|
17 Participants
|
|
Number of Participants With Spasm-free Durations
Spasm Free at Week 32
|
13 Participants
|
SECONDARY outcome
Timeframe: Week 4 through Week 32Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
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.
Outcome measures
| Measure |
Ganaxolone
n=43 Participants
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.
|
|---|---|
|
Number of Participants With Absence of Spasms
Achieved absence of spasms at Week 14
|
3 Participants
|
|
Number of Participants With Absence of Spasms
Achieved absence of spasms at Week 20
|
4 Participants
|
|
Number of Participants With Absence of Spasms
Achieved absence of spasms at Week 26
|
5 Participants
|
|
Number of Participants With Absence of Spasms
Achieved absence of spasms at Week 4
|
2 Participants
|
|
Number of Participants With Absence of Spasms
Achieved absence of spasms at Week 8
|
3 Participants
|
|
Number of Participants With Absence of Spasms
Achieved absence of spasms at Week 32
|
1 Participants
|
SECONDARY outcome
Timeframe: Week 8 through Week 32Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
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.
Outcome measures
| Measure |
Ganaxolone
n=34 Participants
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.
|
|---|---|
|
Developmental Assessment Using Denver-II Developmental Test
Week 8 - Language
|
-1.45 Scores on a scale
Standard Deviation 2.798
|
|
Developmental Assessment Using Denver-II Developmental Test
Week 8 - Gross Motor
|
-1.05 Scores on a scale
Standard Deviation 2.285
|
|
Developmental Assessment Using Denver-II Developmental Test
Week 20- Fine Motor-Adaptive
|
-3.73 Scores on a scale
Standard Deviation 5.123
|
|
Developmental Assessment Using Denver-II Developmental Test
Week 20- Language
|
-2.39 Scores on a scale
Standard Deviation 5.615
|
|
Developmental Assessment Using Denver-II Developmental Test
Week 20 - Gross Motor
|
-2.69 Scores on a scale
Standard Deviation 3.584
|
|
Developmental Assessment Using Denver-II Developmental Test
Week 32-Personal Social
|
-4.86 Scores on a scale
Standard Deviation 5.659
|
|
Developmental Assessment Using Denver-II Developmental Test
Week 32-Fine Motor-Adaptive
|
-6.80 Scores on a scale
Standard Deviation 4.952
|
|
Developmental Assessment Using Denver-II Developmental Test
Week 32-Language
|
-6.58 Scores on a scale
Standard Deviation 4.336
|
|
Developmental Assessment Using Denver-II Developmental Test
Week 32-Gross Motor
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-6.13 Scores on a scale
Standard Deviation 4.509
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Developmental Assessment Using Denver-II Developmental Test
Week 8 - Personal Social
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-0.72 Scores on a scale
Standard Deviation 3.899
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Developmental Assessment Using Denver-II Developmental Test
Week 8 - Fine Motor-Adaptive
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-1.56 Scores on a scale
Standard Deviation 3.131
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Developmental Assessment Using Denver-II Developmental Test
Week 20- Personal Social
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-2.82 Scores on a scale
Standard Deviation 6.081
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SECONDARY outcome
Timeframe: Weeks 4 through Week 32Population: ITT Population. Only those participants with data available at the indicated time point were analyzed.
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.
Outcome measures
| Measure |
Ganaxolone
n=45 Participants
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.
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|---|---|
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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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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 30.140
|
Adverse Events
Ganaxolone
Serious events: 24 serious events
Other events: 47 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Ganaxolone
n=54 participants at risk
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.
|
|---|---|
|
Nervous system disorders
Infantile spasms
|
9.3%
5/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Nervous system disorders
Convulsion
|
7.4%
4/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
General disorders
Pyrexia
|
7.4%
4/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Nervous system disorders
Epilepsy
|
3.7%
2/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Gastroenteritis
|
3.7%
2/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Nasopharyngitis
|
3.7%
2/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Upper respiratory tract infection
|
3.7%
2/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.7%
2/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
3.7%
2/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Metabolism and nutrition disorders
Failure to thrive
|
3.7%
2/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Metabolism and nutrition disorders
Oral intake reduced
|
3.7%
2/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
Other adverse events
| Measure |
Ganaxolone
n=54 participants at risk
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.
|
|---|---|
|
General disorders
Pyrexia
|
48.1%
26/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
35.2%
19/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Upper respiratory tract infection
|
33.3%
18/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Gastrointestinal disorders
Vomiting
|
27.8%
15/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Nasopharyngitis
|
24.1%
13/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
20.4%
11/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Nervous system disorders
Convulsion
|
16.7%
9/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Urinary tract infection
|
14.8%
8/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Gastrointestinal disorders
Diarrhea
|
14.8%
8/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Gastrointestinal disorders
Constipation
|
13.0%
7/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Gastrointestinal disorders
Teething
|
13.0%
7/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Nervous system disorders
Somnolence
|
13.0%
7/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
11.1%
6/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
General disorders
Irritability
|
11.1%
6/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Nervous system disorders
Infantile spasms
|
11.1%
6/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Ear infection
|
9.3%
5/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Influenza
|
9.3%
5/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Rhinitis
|
9.3%
5/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Metabolism and nutrition disorders
Dehydration
|
9.3%
5/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Nervous system disorders
Tonic convulsion
|
7.4%
4/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Metabolism and nutrition disorders
Oral intake reduced
|
7.4%
4/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Psychiatric disorders
Insomnia
|
7.4%
4/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Bronchitis
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Gastroenteritis
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Infections and infestations
Otitis media
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Nervous system disorders
Lethargy
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Investigations
Hemoglobin decreased
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
|
Blood and lymphatic system disorders
Anemia
|
5.6%
3/54 • Up to Week 32
AEs and SAEs were collected in ITT Population. No separate analysis was performed to report results by doses.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place