| Trial | Outcome |
|---|
| NCT00441896 (9) [back to overview] | Developmental Assessment Using Denver-II Developmental Test at Day 20 |
| NCT00441896 (9) [back to overview] | Change From Baseline in Frequency of Spasm Clusters at Day 10 |
| NCT00441896 (9) [back to overview] | Number of Participants With Absence of Hypsarrhythmia |
| NCT00441896 (9) [back to overview] | Change From Baseline in Frequency of Spasm Clusters at Day 20 |
| NCT00441896 (9) [back to overview] | Number of Participants With Spasm-free Durations |
| NCT00441896 (9) [back to overview] | Number of Participants With Seizure-free Days |
| NCT00441896 (9) [back to overview] | Number of Responders |
| NCT00441896 (9) [back to overview] | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment |
| NCT00441896 (9) [back to overview] | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment |
| NCT00442104 (9) [back to overview] | Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary. |
| NCT00442104 (9) [back to overview] | Number of Participants With Change in Clinical Status on Caregiver's Global Assessment |
| NCT00442104 (9) [back to overview] | Number of Participants With Absence of Spasms |
| NCT00442104 (9) [back to overview] | Developmental Assessment Using Denver-II Developmental Test |
| NCT00442104 (9) [back to overview] | Number of Participants With Spasm-free Durations |
| NCT00442104 (9) [back to overview] | Percentage of Participants Who Were Free of Spasms |
| NCT00442104 (9) [back to overview] | Change From Baseline in Frequency of Individual Spasm |
| NCT00442104 (9) [back to overview] | Change From Baseline in Frequency of Spasm Clusters |
| NCT00442104 (9) [back to overview] | Number of Participants With Change in Clinical Status on the Investigator's Global Assessment |
| NCT00465517 (16) [back to overview] | Percent Change From Baseline in Mean Weekly Seizure Frequency by Subtype During Weeks 1 Through 10 |
| NCT00465517 (16) [back to overview] | Percent Change From Baseline in Mean Weekly Seizure Frequency During Weeks 3 Through 10 |
| NCT00465517 (16) [back to overview] | Change From Baseline in Mean Weekly Seizure Frequency During Weeks 1 Through 10 |
| NCT00465517 (16) [back to overview] | Change From Baseline in Mean Weekly Seizure Frequency During Weeks 3 Through 10 |
| NCT00465517 (16) [back to overview] | Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 |
| NCT00465517 (16) [back to overview] | Number of Responders During Weeks 1 Through 10 |
| NCT00465517 (16) [back to overview] | Number of Responders During Weeks 3 Through 10 |
| NCT00465517 (16) [back to overview] | Number of Seizure-free Days During Week 1 Through 10 |
| NCT00465517 (16) [back to overview] | Number of Seizure-free Days During Week 3 Through 10 |
| NCT00465517 (16) [back to overview] | Number of Seizure-free Days Up to Week 2 |
| NCT00465517 (16) [back to overview] | Number of Seizure-free Participants During Weeks 1 Through 10 |
| NCT00465517 (16) [back to overview] | Number of Seizure-free Participants During Weeks 3 Through 10 |
| NCT00465517 (16) [back to overview] | Number of Seizure-free Participants Up to Week 2 |
| NCT00465517 (16) [back to overview] | Percent Change From Baseline in Mean Weekly Seizure Frequency During Weeks 1 Through 10 |
| NCT00465517 (16) [back to overview] | Mean Weekly Log-transformed Seizure Frequency During Weeks 1 Through 10 |
| NCT00465517 (16) [back to overview] | Mean Weekly Log-transformed Seizure Frequency During Weeks 3 Through 10 |
| NCT00512317 (8) [back to overview] | Number of Seizure-free Participants |
| NCT00512317 (8) [back to overview] | Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 |
| NCT00512317 (8) [back to overview] | Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 |
| NCT00512317 (8) [back to overview] | Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire |
| NCT00512317 (8) [back to overview] | Number of Responders During Weeks 1 Through 117 |
| NCT00512317 (8) [back to overview] | Number of Responders During Weeks 1 Through 117 |
| NCT00512317 (8) [back to overview] | Number of Seizure-free Days During Weeks 1 Through 117 |
| NCT00512317 (8) [back to overview] | Number of Seizure-free Days During Weeks 1 Through 117 |
| NCT01002820 (1) [back to overview] | Investigators Global Assessment |
| NCT01339689 (11) [back to overview] | Number of Participants With Response to Clinical Global Impression - Improvement (Investigator) (CGI-II) Scale |
| NCT01339689 (11) [back to overview] | Change From Baseline in Connor-Davidson Resilience Scale (CD-RISC) Score |
| NCT01339689 (11) [back to overview] | Change From Baseline in Insomnia Severity Index (ISI) Score |
| NCT01339689 (11) [back to overview] | Change From Baseline in Patient Health Questionnaire (PHQ-9) Score |
| NCT01339689 (11) [back to overview] | Change From Baseline in Profile of Mood States (POMS) Total Score |
| NCT01339689 (11) [back to overview] | Change From Baseline in Clinician-Administered Posttrautamtic Stress Disorder (PTSD) Scale (CAPS) to Week 6 |
| NCT01339689 (11) [back to overview] | Change From Baseline in PTSD Avoidance Score |
| NCT01339689 (11) [back to overview] | Change From Baseline in PTSD Checklist (PCL) Scores |
| NCT01339689 (11) [back to overview] | Change From Baseline in PTSD Hyperarousal Score |
| NCT01339689 (11) [back to overview] | Change From Baseline in PTSD Re-Experience Score |
| NCT01339689 (11) [back to overview] | Number of Participants With Response to CGI-I Subject Scale Clinical Global Impression - Improvement (Subject) (CGI-IS) Scale |
| NCT01725152 (6) [back to overview] | Clinical Global Impression-Improvement (CGI-I) Scale |
| NCT01725152 (6) [back to overview] | Pediatric Anxiety Rating Scale (PARS) Total Score |
| NCT01725152 (6) [back to overview] | Visual Analogue Scale (VAS) |
| NCT01725152 (6) [back to overview] | Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV) |
| NCT01725152 (6) [back to overview] | Anxiety, Depression, and Mood Scale (ADAMS) |
| NCT01725152 (6) [back to overview] | Aberrant Behavior Checklist (ABC) |
| NCT01857531 (6) [back to overview] | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 2 |
| NCT01857531 (6) [back to overview] | Number of Participants Completing Continuous 6-week Abstinence From Smoking |
| NCT01857531 (6) [back to overview] | Number of Participants Completing Abstinence From Smoking During the Last Four Weeks of Treatment |
| NCT01857531 (6) [back to overview] | Number of Participants Completing Continuous 2-week Abstinence From Smoking |
| NCT01857531 (6) [back to overview] | Number of Participants Completing Point Abstinence From Smoking Two Weeks After Quitting |
| NCT01857531 (6) [back to overview] | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 4 |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Percentage of Responders Experiencing a ≥R% (80%, 60%, 40%, and 20%) Reduction From Baseline to the End of Treatment Period in 28-day Seizure Frequency During Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Percentage of Responders Experiencing a ≥R% (80%, 60%, 40%, and 20%) Reduction From Baseline to the End of Treatment Period in 28-day Seizure Frequency During Titration + Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 8 |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 14 |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Percentage of Seizure Free Participants During the Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Percentage of Participants Who Experienced at Least One 28-day Seizure Free Period During Titration + Maintenance Phase |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency for Different Subtypes of Seizures During Titration + Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Number of Participants With Patient Global Impression of Change - Improvement (PGI-I) at Week 8 and Week 14 |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Longest Percent of Time Spent Seizure-free During Titration + Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Titration + Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Maintenance Period |
| NCT01963208 (16) [back to overview] | Double Blind: Cohort 2: Number of Participants With ≥50% Responder Rate During Titration + Maintenance Period |
| NCT02358538 (6) [back to overview] | Summary of CGII-P |
| NCT02358538 (6) [back to overview] | Summary of CGII-C |
| NCT02358538 (6) [back to overview] | Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters Through 52-week OLE (Median Percent Change) |
| NCT02358538 (6) [back to overview] | Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters for 52-week OLE Period (Mean Percent Change & Standard Deviation) |
| NCT02358538 (6) [back to overview] | Number of Participants With Responder Rate of Seizure Frequency |
| NCT02358538 (6) [back to overview] | Mean Percentage Change of Individual Seizure-free Days |
| NCT02519439 (4) [back to overview] | Number of Participants Who Showed Greater Than or Equal to 50% Reduction in 28-day Seizure Frequent From Baseline |
| NCT02519439 (4) [back to overview] | Percent Change From Baseline in 28-day Seizure Frequency |
| NCT02519439 (4) [back to overview] | Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores |
| NCT02519439 (4) [back to overview] | Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores |
| NCT02900092 (1) [back to overview] | Montgomery-Asberg Depression Rating Scale (MADRS) |
| NCT03228394 (14) [back to overview] | Change From Baseline in Spielberger State-Trait Anxiety Inventory 6-item Version (STAI6) Total Score |
| NCT03228394 (14) [back to overview] | Change From Baseline in Spielberger State-Trait Anxiety Inventory 6-item Version (STAI6) Total Score |
| NCT03228394 (14) [back to overview] | Number of Participants With HAMD17 Remission |
| NCT03228394 (14) [back to overview] | Change From Baseline in HAMD17 Total Score at Indicated Time Points |
| NCT03228394 (14) [back to overview] | Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Total Score |
| NCT03228394 (14) [back to overview] | Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Total Score |
| NCT03228394 (14) [back to overview] | Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score |
| NCT03228394 (14) [back to overview] | Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score |
| NCT03228394 (14) [back to overview] | Change From Baseline in HAMD17 Total Score at Indicated Time Points |
| NCT03228394 (14) [back to overview] | Number of Participants With HAMD17 Remission |
| NCT03228394 (14) [back to overview] | Number of Participants With HAMD17 Response |
| NCT03228394 (14) [back to overview] | Number of Participants With HAMD17 Response |
| NCT03228394 (14) [back to overview] | Number of Participants With Response to Clinical Global Impression-Improvement (CGI-I) Scale |
| NCT03228394 (14) [back to overview] | Number of Participants With Response to Clinical Global Impression-Improvement (CGI-I) Scale |
| NCT03350035 (5) [back to overview] | Seizure Burden |
| NCT03350035 (5) [back to overview] | Number of Participants With No SE Recurrence Per Principal Investigator |
| NCT03350035 (5) [back to overview] | Time to Cessation of SE |
| NCT03350035 (5) [back to overview] | Number of Participants Who Required No Escalation of Treatment for Ongoing or Recurrent SE |
| NCT03350035 (5) [back to overview] | Number of Participants Who Did Not Require an IV Anesthetic Drug for SE Treatment |
| NCT03460756 (20) [back to overview] | Change From Baseline in Spielberger State-Trait Anxiety Inventory, 6-item Version |
| NCT03460756 (20) [back to overview] | Change From Baseline in Hamilton Depression Rating Scale 17-item Version Post Treatment |
| NCT03460756 (20) [back to overview] | Change From Baseline in Hamilton Depression Rating Scale 17-item Version Post Treatment |
| NCT03460756 (20) [back to overview] | Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Through Treatment |
| NCT03460756 (20) [back to overview] | Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Through Treatment |
| NCT03460756 (20) [back to overview] | Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score |
| NCT03460756 (20) [back to overview] | Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score |
| NCT03460756 (20) [back to overview] | Change From Baseline in Hamilton Depression Rating Scale 17-item Version Post Treatment |
| NCT03460756 (20) [back to overview] | Number of Participants With Clinical Global Impression-Improvement |
| NCT03460756 (20) [back to overview] | Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score |
| NCT03460756 (20) [back to overview] | Number of Participants With Clinical Global Impression-Improvement |
| NCT03460756 (20) [back to overview] | Number of Participants With Clinical Global Impression-Improvement |
| NCT03460756 (20) [back to overview] | Change From Baseline in Spielberger State-Trait Anxiety Inventory, 6-item Version |
| NCT03460756 (20) [back to overview] | Change From Baseline in Spielberger State-Trait Anxiety Inventory, 6-item Version |
| NCT03460756 (20) [back to overview] | Number of Participants With Response to Hamilton Depression Rating Scale 17 Item (HAMD17) |
| NCT03460756 (20) [back to overview] | Number of Participants With Response to Hamilton Depression Rating Scale 17 Item (HAMD17) |
| NCT03460756 (20) [back to overview] | Number of Participants With Hamilton Depression Rating Scale 17-item Remission |
| NCT03460756 (20) [back to overview] | Number of Participants With Response to Hamilton Depression Rating Scale 17 Item (HAMD17) |
| NCT03460756 (20) [back to overview] | Number of Participants With Hamilton Depression Rating Scale 17-item Remission |
| NCT03460756 (20) [back to overview] | Number of Participants With Hamilton Depression Rating Scale 17-item Remission |
| NCT03572933 (8) [back to overview] | Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types |
| NCT03572933 (8) [back to overview] | Caregiver Global Impression of Change in Attention |
| NCT03572933 (8) [back to overview] | Caregiver Global Impression of Change in Seizure Intensity and Duration |
| NCT03572933 (8) [back to overview] | Caregiver Global Impression of Change in Target Behavior |
| NCT03572933 (8) [back to overview] | Clinical Global Impression of Improvement - Clinician |
| NCT03572933 (8) [back to overview] | Clinical Global Impression of Improvement - Parent/Caregiver |
| NCT03572933 (8) [back to overview] | Percentage of Seizure-free Days for Major Motor Seizure Types |
| NCT03572933 (8) [back to overview] | Summary of 28-day Seizure Frequency for Major Motor Seizure Types |
| NCT03865732 (3) [back to overview] | 50% Primary Seizure Reduction |
| NCT03865732 (3) [back to overview] | Summary of 28-day Seizure Frequency for Subjects in the Biomarker-positive Stratum (Median Percent Change) |
| NCT03865732 (3) [back to overview] | Summary of 28-day Seizure Frequency Through 17 Week Post-Baseline Phase (Median Percent Change) |
| NCT04285346 (2) [back to overview] | Percent Change From Baseline in 28-day Seizure Frequency Through the End of 12-Week Treatment Period |
| NCT04285346 (2) [back to overview] | Percentage of Participants Experiencing a >=50 Percent Reduction in 28-day Primary Seizure Frequency Through the End of the 12-week Treatment Period Compared to the Baseline Period |
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. (NCT00441896)
Timeframe: At Day 20
| Intervention | Scores on a scale (Mean) |
|---|
| Personal Social at Day 20 | Fine Motor Adaptive at Day 20 | Language at Day 20 | Gross Motor at Day 20 |
|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | -5.48 | -4.38 | -1.36 | -3.96 |
,| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | -16.90 | -14.63 | -12.33 | -13.63 |
,| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | -8.79 | -7.49 | -7.23 | -7.16 |
,| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | -8.73 | -7.70 | -5.17 | -7.00 |
,| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | -7.76 | -6.40 | -5.82 | -5.58 |
,| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | -5.35 | -5.05 | -4.95 | -3.00 |
,| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | -5.99 | -6.16 | -6.09 | -6.89 |
,| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | -10.22 | -10.24 | -8.22 | -8.74 |
,| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | -7.72 | -8.32 | -7.44 | -8.76 |
,| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | -12.93 | -12.87 | -10.77 | -13.43 |
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. (NCT00441896)
Timeframe: Baseline (Day 0) and Day 10
| Intervention | Spasm clusters per day (Mean) |
|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | 1.0 |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | 2.7 |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | -5.4 |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | -1.0 |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | -1.4 |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | -5.3 |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | -3.7 |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | 0.2 |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | -3.2 |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | -1.7 |
Number of Participants With Absence of Hypsarrhythmia
Absence of hypsarrhythmia was determined by 24-hour vEEG at Day 10 and Day 20. (NCT00441896)
Timeframe: Day 10 and Day 20
| Intervention | Participants (Count of Participants) |
|---|
| Day 10 | Day 20 |
|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | 1 | 1 |
,| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 |
,| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | 2 | 2 |
,| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 |
,| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | 2 | 2 |
,| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 |
,| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | 2 | 2 |
,| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | 2 | 2 |
,| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | 1 | 3 |
,| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 |
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. (NCT00441896)
Timeframe: Baseline (Day 0) and Day 20
| Intervention | Spasm clusters per day (Mean) |
|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | -3.2 |
| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | 6.0 |
| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | -5.0 |
| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | -1.5 |
| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | -1.1 |
| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | -12.7 |
| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | -4.4 |
| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | -1.2 |
| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | -3.2 |
| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | -5.3 |
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. (NCT00441896)
Timeframe: Day 10 and Day 20
| Intervention | Participants (Count of Participants) |
|---|
| Spasm-free Durations at Day 10 | Spasm-free Durations at Day 20 |
|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | 3 | 3 |
,| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | 1 | 1 |
,| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | 3 | 2 |
,| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | 2 | 2 |
,| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | 2 | 2 |
,| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 1 |
,| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | 3 | 1 |
,| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 1 |
,| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | 1 | 0 |
,| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 |
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. (NCT00441896)
Timeframe: From Day 8 to Day 10 and From Day 18 to Day 20
| Intervention | Participants (Count of Participants) |
|---|
| From Day 8 to Day 10 | From Day 18 to Day 20 |
|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | 6 | 6 |
,| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | 2 | 1 |
,| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | 6 | 6 |
,| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | 3 | 4 |
,| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | 10 | 10 |
,| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | 3 | 3 |
,| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | 6 | 6 |
,| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | 5 | 5 |
,| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | 6 | 6 |
,| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | 3 | 3 |
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 (NCT00441896)
Timeframe: Day 10 and Day 20
| Intervention | Participants (Count of Participants) |
|---|
| Day 10 | Day 20 |
|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | 2 | 2 |
,| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | 1 | 0 |
,| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | 3 | 4 |
,| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 2 |
,| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | 3 | 3 |
,| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 1 |
,| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | 2 | 4 |
,| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | 2 | 1 |
,| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | 2 | 1 |
,| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | 1 | 1 |
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. (NCT00441896)
Timeframe: Baseline (Day 0), Day 10 and Day 20
| Intervention | Participants (Count of Participants) |
|---|
| Marked improvement at Day 10 | Moderate improvement at Day 10 | Slight improvement at Day 10 | No change from Baseline at Day 10 | Slight worsening at Day 10 | Moderate worsening at Day 10 | Severe worsening at Day 10 | Marked improvement at Day 20 | Moderate improvement at Day 20 | Slight improvement at Day 20 | No change from Baseline at Day 20 | Slight worsening at Day 20 | Moderate worsening at Day 20 | Severe worsening at Day 20 |
|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | 1 | 0 | 1 | 4 | 0 | 0 | 0 | 2 | 1 | 2 | 1 | 0 | 0 | 0 |
,| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | 0 | 2 | 1 | 4 | 0 | 0 | 0 | 1 | 1 | 3 | 2 | 0 | 0 | 0 |
,| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 1 | 3 | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 0 | 0 | 0 |
,| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | 1 | 0 | 2 | 7 | 0 | 0 | 0 | 1 | 1 | 6 | 2 | 0 | 0 | 0 |
,| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 |
,| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | 0 | 1 | 2 | 4 | 0 | 0 | 0 | 0 | 2 | 2 | 3 | 0 | 0 | 0 |
,| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 1 | 3 | 1 | 0 | 0 | 0 |
,| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | 0 | 1 | 2 | 3 | 0 | 0 | 0 | 0 | 1 | 4 | 1 | 0 | 0 | 0 |
,| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 |
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. (NCT00441896)
Timeframe: Baseline (Day 0), Day10 and Day 20
| Intervention | Participants (Count of Participants) |
|---|
| Marked improvement at Day 10 | Moderate improvement at Day 10 | Slight improvement at Day 10 | No change from Baseline at Day 10 | Slight worsening at Day 10 | Moderate worsening at Day 10 | Severe worsening at Day 10 | Marked improvement at Day 20 | Moderate improvement at Day 20 | Slight improvement at Day 20 | No change from Baseline at Day 20 | Slight worsening at Day 20 | Moderate worsening at Day 20 | Severe worsening at Day 20 |
|---|
| Cohort 1: Sequence A: Ganaxolone/Placebo/Ganaxolone | 1 | 0 | 1 | 4 | 0 | 0 | 0 | 2 | 1 | 2 | 1 | 0 | 0 | 0 |
,| Cohort 1: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 2: Sequence A: Ganaxolone/Placebo/Ganaxolone | 0 | 2 | 1 | 4 | 0 | 0 | 0 | 1 | 1 | 2 | 3 | 0 | 0 | 0 |
,| Cohort 2: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 0 | 0 | 0 |
,| Cohort 3: Sequence A: Ganaxolone/Placebo/Ganaxolone | 1 | 0 | 5 | 4 | 0 | 0 | 0 | 1 | 1 | 6 | 2 | 0 | 0 | 0 |
,| Cohort 3: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
,| Cohort 4: Sequence A: Ganaxolone/Placebo/Ganaxolone | 0 | 1 | 2 | 3 | 1 | 0 | 0 | 0 | 2 | 3 | 2 | 0 | 0 | 0 |
,| Cohort 4: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 3 | 2 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 1 | 0 | 0 |
,| Cohort 5: Sequence A: Ganaxolone/Placebo/Ganaxolone | 0 | 1 | 2 | 3 | 0 | 0 | 0 | 0 | 1 | 4 | 1 | 0 | 0 | 0 |
,| Cohort 5: Sequence B: Placebo/Ganaxolone/Placebo | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 |
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." (NCT00442104)
Timeframe: Weeks 4 through Week 32
| Intervention | Percentage of Days (Mean) |
|---|
| Total Spasm-free days during Week 4 visit | Total Spasm-free days during Week 8 visit | Total Spasm-free days during Week 14 visit | Total Spasm-free days during Week 20 visit | Total Spasm-free days during Week 26 visit | Total Spasm-free days during week 32 visit | Cumulative Spasm-free days during Week 4 visit | Cumulative Spasm-free days during Week 8 visit | Cumulative Spasm-free days during Week 14 visit | Cumulative Spasm-free days during Week 20 visit | Cumulative Spasm-free days during Week 26 visit | Cumulative Spasm-free days during Week 32 visit |
|---|
| Ganaxolone | 11.10 | 18.74 | 20.74 | 28.79 | 28.73 | 27.99 | 10.86 | 13.82 | 15.70 | 19.97 | 22.07 | 22.99 |
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. (NCT00442104)
Timeframe: Week 4 through Week 32
| Intervention | participants (Number) |
|---|
| Caregiver's- Week 4 - Marked Improvement | Caregiver's - Week 4 - Moderate Improvement | Caregiver's -Week 4 - Slight Improvement | Caregiver's- Week 4 - No change from Baseline | Caregiver's - Week 4 - Moderate Worsening | Caregiver's - Week 4 - Slight Worsening | Caregiver's - Week 4 - Marked Worsening | Caregiver's - Week 8 - Marked Improvement | Caregiver's- Week 8 - Moderate Improvement | Caregiver's -Week 8 - Slight Improvement | Caregiver's- Week 8 - No change from Baseline | Caregiver's - Week 8 - Slight Worsening | Caregiver's - Week 8 - Moderate Worsening | Caregiver's - Week 8 - Marked Worsening | Caregiver's- Week 14 - Marked Improvement | Caregiver's - Week 14 - Moderate Improvement | Caregiver's -Week 14 - Slight Improvement | Caregiver's - Week 14 - No change from Baseline | Caregiver's - Week 14 - Slight Worsening | Caregiver's - Week 14 - Moderate Worsening | Caregiver's - Week 14 - Marked Worsening | Caregiver's - Week 20 - Marked Improvement | Caregiver's - Week 20 - Moderate Improvement | Caregiver's -Week 20 - Slight Improvement | Caregiver's- Week 20 - No change from Baseline | Caregiver's- Week 20 - Slight Worsening | Caregiver's - Week 20 - Moderate Worsening | Caregiver's - Week 20 - Marked Worsening | Caregiver's- Week 26 - Marked Improvement | Caregiver's- Week 26 - Moderate Improvement | Caregiver's -Week 26 - Slight Improvement | Caregiver's - Week 26 - No change from Baseline | Caregiver's - Week 26 - Slight Worsening | Caregiver's - Week 26 - Moderate Worsening | Caregiver's - Week 26 - Marked Worsening | Caregiver's - Week 32 - Marked Improvement | Caregiver's - Week 32 - Moderate Improvement | Caregiver's-Week 32 - Slight Improvement | Caregiver's - Week 32 - No change from Baseline | Caregiver's - Week 32 - Slight Worsening | Caregiver's - Week 32 - Moderate Worsening | Caregiver's - Week 32 - Marked Worsening |
|---|
| Ganaxolone | 11 | 11 | 16 | 6 | 0 | 1 | 0 | 7 | 12 | 18 | 1 | 2 | 0 | 0 | 8 | 13 | 14 | 2 | 1 | 0 | 0 | 9 | 13 | 10 | 3 | 1 | 0 | 0 | 9 | 12 | 7 | 3 | 0 | 0 | 0 | 8 | 7 | 8 | 2 | 0 | 1 | 0 |
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. (NCT00442104)
Timeframe: Week 4 through Week 32
| Intervention | Participants (Count of Participants) |
|---|
| Achieved absence of spasms at Week 4 | Achieved absence of spasms at Week 8 | Achieved absence of spasms at Week 14 | Achieved absence of spasms at Week 20 | Achieved absence of spasms at Week 26 | Achieved absence of spasms at Week 32 |
|---|
| Ganaxolone | 2 | 3 | 3 | 4 | 5 | 1 |
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. (NCT00442104)
Timeframe: Week 8 through Week 32
| Intervention | Scores on a scale (Mean) |
|---|
| Week 8 - Personal Social | Week 8 - Fine Motor-Adaptive | Week 8 - Language | Week 8 - Gross Motor | Week 20- Personal Social | Week 20- Fine Motor-Adaptive | Week 20- Language | Week 20 - Gross Motor | Week 32-Personal Social | Week 32-Fine Motor-Adaptive | Week 32-Language | Week 32-Gross Motor |
|---|
| Ganaxolone | -0.72 | -1.56 | -1.45 | -1.05 | -2.82 | -3.73 | -2.39 | -2.69 | -4.86 | -6.80 | -6.58 | -6.13 |
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. (NCT00442104)
Timeframe: Week 4 through Week 32
| Intervention | Participants (Count of Participants) |
|---|
| Spasm Free at Week 4 | Spasm Free at Week 8 | Spasm Free at Week 14 | Spasm Free at Week 20 | Spasm Free at Week 26 | Spasm Free at Week 32 |
|---|
| Ganaxolone | 19 | 18 | 18 | 18 | 17 | 13 |
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. (NCT00442104)
Timeframe: Weeks 4 through Week 96
| Intervention | percentage of participants (Number) |
|---|
| Ganaxolone | 100 |
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. (NCT00442104)
Timeframe: Baseline and Week 4 through Week 32
| Intervention | Individual spasms per day (Mean) |
|---|
| Individual Spasms - Week 4 | Individual Spasms - Week 8 | Individual Spasms - Week 14 | Individual Spasms - Week 20 | Individual Spasms - Week 26 | Individual Spasms - Week 32 |
|---|
| Ganaxolone | -6.8 | -17.4 | -20.8 | -15.8 | -19.9 | -17.7 |
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. (NCT00442104)
Timeframe: Baseline and Week 4 through Week 32
| Intervention | Spasm clusters per day (Mean) |
|---|
| Spasm Clusters - Week 4 | Spasm Clusters - Week 8 | Spasm Clusters - Week 14 | Spasm Clusters - Week 20 | Spasm Clusters - Week 26 | Spasm Clusters - Week 32 |
|---|
| Ganaxolone | -2.9 | -4.1 | -4.1 | -5.8 | -5.6 | -5.3 |
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. (NCT00442104)
Timeframe: Week 4 through Week 32
| Intervention | participants (Number) |
|---|
| Investigator's- Week 4 - Marked Improvement | Investigator's - Week 4 - Moderate Improvement | Investigator's -Week 4 - Slight Improvement | Investigator's- Week 4 - No change from Baseline | Investigator's - Week 4 - Moderate Worsening | Investigator's - Week 4 - Slight Worsening | Investigator's - Week 4 - Marked Worsening | Investigator's - Week 8 - Marked Improvement | Investigator's- Week 8 - Moderate Improvement | Investigator's -Week 8 - Slight Improvement | Investigator's- Week 8 - No change from Baseline | Investigator's - Week 8 - Slight Worsening | Investigator's - Week 8 - Moderate Worsening | Investigator's - Week 8 - Marked Worsening | Investigator's- Week 14 - Marked Improvement | Investigator's - Week 14 - Moderate Improvement | Investigator's -Week 14 - Slight Improvement | Investigator's - Week 14 - No change from Baseline | Investigator's - Week 14 - Slight Worsening | Investigator's - Week 14 - Moderate Worsening | Investigator's - Week 14 - Marked Worsening | Investigator's - Week 20 - Marked Improvement | Investigator's - Week 20 - Moderate Improvement | Investigator's -Week 20 - Slight Improvement | Investigator's- Week 20 - No change from Baseline | Investigator's- Week 20 - Slight Worsening | Investigator's - Week 20 - Moderate Worsening | Investigator's - Week 20 - Marked Worsening | Investigator's- Week 26 - Marked Improvement | Investigator's- Week 26 - Moderate Improvement | Investigator's -Week 26 - Slight Improvement | Investigator's - Week 26 - No change from Baseline | Investigator's - Week 26 - Slight Worsening | Investigator's - Week 26 - Moderate Worsening | Investigator's - Week 26 - Marked Worsening | Investigator's - Week 32 - Marked Improvement | Investigator's - Week 32 - Moderate Improvement | Investigator's -Week 32 - Slight Improvement | Investigator's - Week 32 - No change from Baseline | Investigator's - Week 32 - Slight Worsening | Investigator's - Week 32 - Moderate Worsening | Investigator's - Week 32 - Marked Worsening |
|---|
| Ganaxolone | 7 | 15 | 18 | 4 | 1 | 0 | 0 | 6 | 12 | 19 | 3 | 0 | 0 | 0 | 6 | 16 | 15 | 1 | 0 | 0 | 0 | 7 | 14 | 11 | 1 | 1 | 0 | 0 | 5 | 14 | 9 | 4 | 0 | 0 | 0 | 6 | 9 | 8 | 3 | 1 | 0 | 0 |
Percent Change From Baseline in Mean Weekly Seizure Frequency by Subtype During Weeks 1 Through 10
Seizure subtypes included Complex partial seizures (CPS), Generalized tonic-clonic seizure (GTCS), and Simple partial seizure (SPS)-motor. Percent Change from Baseline in Mean Weekly Seizure frequency by seizure subtype is presented. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT00465517)
Timeframe: Baseline and at Week 1 through Week 10
| Intervention | Percent change (Mean) |
|---|
| CPS | GTC | SPS-motor |
|---|
| Ganaxolone | -17.47 | -30.65 | -30.63 |
,| Placebo | 3.88 | -37.75 | 19.70 |
Percent Change From Baseline in Mean Weekly Seizure Frequency During Weeks 3 Through 10
Summary of percent change from Baseline in mean weekly seizure frequency is presented. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT00465517)
Timeframe: Baseline and at Week 3 through Week 10
| Intervention | Percent change (Mean) |
|---|
| Ganaxolone | -12.08 |
| Placebo | 4.57 |
Change From Baseline in Mean Weekly Seizure Frequency During Weeks 1 Through 10
Summary of change from Baseline in mean weekly seizure frequency is presented. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT00465517)
Timeframe: Baseline and at Week 1 through Week 10
| Intervention | Seizures per week (Mean) |
|---|
| Ganaxolone | -1.27 |
| Placebo | 1.41 |
Change From Baseline in Mean Weekly Seizure Frequency During Weeks 3 Through 10
Summary of change from Baseline in mean weekly seizure frequency is presented. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT00465517)
Timeframe: Baseline and at Week 3 through Week 10
| Intervention | Seizures per week (Mean) |
|---|
| Ganaxolone | -1.07 |
| Placebo | 2.52 |
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10
Mean weekly Seizure Frequency for each week post-dosing During Weeks 1 to 10 is presented. (NCT00465517)
Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10
| Intervention | Seizures per week (Mean) |
|---|
| Week 1 | Week 2 | Week 3 | Week 4 | Week 5 | Week 6 | Week 7 | Week 8 | Week 9 | Week 10 |
|---|
| Ganaxolone | 4.53 | 5.09 | 5.02 | 5.69 | 5.12 | 5.65 | 6.68 | 4.63 | 5.07 | 4.83 |
,| Placebo | 7.25 | 8.79 | 7.80 | 9.13 | 11.64 | 10.43 | 13.15 | 13.47 | 11.64 | 13.60 |
Number of Responders During Weeks 1 Through 10
Responders were defined as participants experiencing ≥50% of reduction in mean weekly seizure frequency from the Baseline. Baseline was defined as the Day 0 assessment before study drug infusion. (NCT00465517)
Timeframe: Baseline and at Week 1 through Week 10
| Intervention | Participants (Count of Participants) |
|---|
| Ganaxolone | 23 |
| Placebo | 7 |
Number of Responders During Weeks 3 Through 10
Responders were defined as participants experiencing ≥50% of reduction in mean weekly seizure frequency from the Baseline. Baseline was defined as the Day 0 assessment before study drug infusion. (NCT00465517)
Timeframe: Baseline and at Week 3 through Week 10
| Intervention | Participants (Count of Participants) |
|---|
| Ganaxolone | 25 |
| Placebo | 6 |
Number of Seizure-free Days During Week 1 Through 10
Summary of Seizure-Free days is presented. (NCT00465517)
Timeframe: Week 1 through Week 10
| Intervention | Seizure free days (Mean) |
|---|
| Ganaxolone | 45.9 |
| Placebo | 46.8 |
Number of Seizure-free Days During Week 3 Through 10
Summary of Seizure-Free days is presented. (NCT00465517)
Timeframe: Week 3 through Week 10
| Intervention | Seizure free days (Mean) |
|---|
| Ganaxolone | 37.1 |
| Placebo | 38.5 |
Number of Seizure-free Days Up to Week 2
Summary of Seizure-Free days is presented. (NCT00465517)
Timeframe: Up to Week 2
| Intervention | Seizure free days (Mean) |
|---|
| Ganaxolone | 10.3 |
| Placebo | 10.0 |
Number of Seizure-free Participants During Weeks 1 Through 10
Number of seizure-free participants is presented. (NCT00465517)
Timeframe: Week 1 through Week 10
| Intervention | Participants (Count of Participants) |
|---|
| Ganaxolone | 1 |
| Placebo | 0 |
Number of Seizure-free Participants During Weeks 3 Through 10
Number of seizure-free participants is presented. (NCT00465517)
Timeframe: Week 3 through Week 10
| Intervention | Participants (Count of Participants) |
|---|
| Ganaxolone | 0 |
| Placebo | 1 |
Number of Seizure-free Participants Up to Week 2
Number of seizure-free participants is presented. (NCT00465517)
Timeframe: Up to Week 2
| Intervention | Participants (Count of Participants) |
|---|
| Ganaxolone | 16 |
| Placebo | 4 |
Percent Change From Baseline in Mean Weekly Seizure Frequency During Weeks 1 Through 10
Summary of percent change from Baseline in mean weekly seizure frequency is presented. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT00465517)
Timeframe: Baseline and at Week 1 through Week 10
| Intervention | Percent change (Mean) |
|---|
| Ganaxolone | -17.59 |
| Placebo | 1.99 |
Number of Seizure-free Participants
Number of Seizure-free participants is presented. (NCT00512317)
Timeframe: Day 1 through Day 224 (Week 32)
| Intervention | Participants (Count of Participants) |
|---|
| >=1 day | >= 28 days (4 weeks) | >= 56 days (8 weeks) | >=70 days (10 weeks) | >=91 days (13 weeks) | >=119 days (17 weeks) | >=133 days (19 weeks) | >=154 days (22 weeks) | >=182 days (26 weeks) | >=224 days (32 weeks) |
|---|
| GNX/GNX | 75 | 20 | 6 | 4 | 4 | 43 | 3 | 3 | 0 | 0 |
,| PBO/GNX | 41 | 38 | 33 | 31 | 29 | 27 | 27 | 25 | 20 | 18 |
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117
Percent Change in weekly seizure frequency by treatment group compared to Baseline at the beginning of the double-blind study 1042-0600 is presented. Weekly seizure frequency included partial-onset seizures (POS) with or without secondary generalization, but not non-motor simple partial seizure (SPS) during Weeks 1 through Week 117. Baseline was defined as the Day 0 assessment before study drug infusion of the double-blind study 1042-0600. (NCT00512317)
Timeframe: Baseline (Day 0) and Week 1 through Week 117
| Intervention | Percent Change (Mean) |
|---|
| Weeks 1-10 | Weeks 1-13 | Weeks >13-26 | Weeks >26-39 | Weeks >39-52 | Weeks >52-65 | Weeks >65-78 | Weeks >78-91 | Weeks >91-104 | Weeks >104-117 |
|---|
| GNX/GNX | -14.8 | -14.0 | -19.6 | -37.7 | -29.1 | -29.9 | -41.4 | -38.8 | -69.4 | -93.3 |
Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117
Percent Change in weekly seizure frequency by treatment group compared to Baseline at the beginning of the double-blind study 1042-0600 is presented. Weekly seizure frequency included partial-onset seizures (POS) with or without secondary generalization, but not non-motor simple partial seizure (SPS) during Weeks 1 through Week 117. Baseline was defined as the Day 0 assessment before study drug infusion of the double-blind study 1042-0600. (NCT00512317)
Timeframe: Baseline (Day 0) and Week 1 through Week 117
| Intervention | Percent Change (Mean) |
|---|
| Weeks 1-10 | Weeks 1-13 | Weeks >13-26 | Weeks >26-39 | Weeks >39-52 | Weeks >52-65 | Weeks >65-78 | Weeks >78-91 | Weeks >91-104 |
|---|
| PBO/GNX | -12.3 | -13.7 | -19.8 | -48.6 | -42.9 | -43.1 | -67.7 | -43.6 | -100 |
Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire
QOLIE-31 was a survey of health-related QOL for adults with epilepsy and evaluated how much distress the participant feels about problems and worries related to epilepsy. It included 38 items grouped into eight multi-item subscales - Energy/Fatigue, Emotional Well-Being, Daily Activities/Social Functioning, Cognitive Functioning, Medication Effect, Seizure Worry, Overall Quality of Life (QoL) and Distress. The subscale scores and the total score were calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100; higher scores indicated better function. Baseline was defined as the last non-missing observation prior to the first dose in double-blind study 1042-0600. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT00512317)
Timeframe: Baseline (Day 0) and up to Week 104
| Intervention | Scores on a Scale (Mean) |
|---|
| Energy/Fatigue | Emotional Well-Being | Social Function | Cognitive | Medication Effect | Seizure Worry | Overall QoL | Distress |
|---|
| GNX/GNX | -5.7 | -4.7 | -3.6 | 2.1 | -3.9 | 3.6 | -3.8 | -5.5 |
,| PBO/GNX | 3.9 | 3.3 | 8.4 | 2.9 | 0.9 | -3.1 | 0.0 | 0.7 |
Number of Responders During Weeks 1 Through 117
Responders were defined as participants experiencing ≥50% of reduction in mean weekly seizure frequency from the Baseline. Baseline was defined as the Day 0 assessment before study drug infusion of the double-blind study 1042-0600. (NCT00512317)
Timeframe: Baseline (Day 0) and Week 1 through Week 117
| Intervention | Participants (Count of Participants) |
|---|
| Weeks 1-10 | Weeks 1-13 | Weeks >13-26 | Weeks >26-39 | Weeks >39-52 | Weeks >52-65 | Weeks >65-78 | Weeks >78-91 | Weeks >91-104 | Weeks >104-117 |
|---|
| GNX/GNX | 22 | 19 | 12 | 11 | 10 | 8 | 6 | 4 | 3 | 1 |
Number of Responders During Weeks 1 Through 117
Responders were defined as participants experiencing ≥50% of reduction in mean weekly seizure frequency from the Baseline. Baseline was defined as the Day 0 assessment before study drug infusion of the double-blind study 1042-0600. (NCT00512317)
Timeframe: Baseline (Day 0) and Week 1 through Week 117
| Intervention | Participants (Count of Participants) |
|---|
| Weeks 1-10 | Weeks 1-13 | Weeks >13-26 | Weeks >26-39 | Weeks >39-52 | Weeks >52-65 | Weeks >65-78 | Weeks >78-91 | Weeks >91-104 |
|---|
| PBO/GNX | 11 | 12 | 8 | 12 | 10 | 8 | 11 | 4 | 1 |
Number of Seizure-free Days During Weeks 1 Through 117
Average number of seizure-free days per week for a given period was calculated as follows: (Total number of days with no seizures of any type during that period / number of days with seizure diary in that period) multiplied by 7. (NCT00512317)
Timeframe: Week 1 through Week 117
| Intervention | Seizure free days (Mean) |
|---|
| Weeks 1-10 | Weeks 1-13 | Weeks >13-26 | Weeks >26-39 | Weeks >39-52 | Weeks >52-65 | Weeks >65-78 | Weeks >78-91 | Weeks >91-104 | Weeks >104-117 |
|---|
| GNX/GNX | 4.8 | 4.8 | 5.1 | 5.2 | 5.4 | 5.1 | 5.3 | 5.4 | 5.6 | 6.9 |
Number of Seizure-free Days During Weeks 1 Through 117
Average number of seizure-free days per week for a given period was calculated as follows: (Total number of days with no seizures of any type during that period / number of days with seizure diary in that period) multiplied by 7. (NCT00512317)
Timeframe: Week 1 through Week 117
| Intervention | Seizure free days (Mean) |
|---|
| Weeks 1-10 | Weeks 1-13 | Weeks >13-26 | Weeks >26-39 | Weeks >39-52 | Weeks >52-65 | Weeks >65-78 | Weeks >78-91 | Weeks >91-104 |
|---|
| PBO/GNX | 5.0 | 5.0 | 5.3 | 5.4 | 5.4 | 5.2 | 5.7 | 4.7 | 6.8 |
Investigators Global Assessment
Investigator's global assessment of the patient's response to ganaxolone treatment was collected during the study to support continued trial participation. The investigator's global assessment of the patient's response to ganaxolone treatment was collected during the study to support continued trial participation. Responses categories were Improved Markedly, Improved Moderately, Improved Slightly and No change from baseline. (NCT01002820)
Timeframe: Screening through 52 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Improved Markedly - Visit 1 - Screening | Improved Moderately - Visit 1 - Screening | Improved Slightly - Visit 1 - Screening | No change from baseline - Visit 1 - Screening | Improved Markedly - Visit 2 - Week 26 | Improved Moderately - Visit 2 - Week 26 | Improved Slightly - Visit 2 - Week 26 | No change from baseline - Visit 2 - Week 26 | Improved Markedly - Visit 3 - Week 52 or Taper Visit | Improved Moderately - Visit 3 - Week 52 or Taper Visit | Improved Slightly - Visit 3 - Week 52 or Taper Visit | No change from baseline - Visit 3 - Week 52 or Taper Visit |
|---|
| Ganaxolone | 6 | 4 | 0 | 1 | 3 | 4 | 0 | 0 | 2 | 4 | 1 | 1 |
Number of Participants With Response to Clinical Global Impression - Improvement (Investigator) (CGI-II) Scale
The CGI-II scale is a 7-point scale where the investigator was required to assess how much the participant's illness has improved or worsened relative to a Baseline state at the beginning of the intervention, and rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Higher score indicated worse symptoms. The score was grouped into two categories for analysis: Responders=1 or 2, Non-responders=3-7. (NCT01339689)
Timeframe: Week 2, Week 4 and Week 6
| Intervention | Participants (Count of Participants) |
|---|
| Week 2 - Non-Responder | Week 2 - Responder | Week 4 - Non-Responder | Week 4 - Responder | Week 6 - Non-Responder | Week 6 - Responder |
|---|
| Ganaxolone | 45 | 3 | 38 | 5 | 27 | 14 |
,| Placebo | 42 | 7 | 37 | 9 | 32 | 12 |
Change From Baseline in Connor-Davidson Resilience Scale (CD-RISC) Score
The CD-RISC comprises 25 items, each rated on a 5-point scale (0-4), with higher scores reflecting greater resilience that may be a target for treatment in stress disorders. The total score is the sum of 25 item scores and ranged from 0: no symptoms to 100: worse symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value (NCT01339689)
Timeframe: Baseline (Week 0) and Week 6
| Intervention | Scores on a scale (Mean) |
|---|
| Placebo | 60.84 |
| Ganaxolone | 61.01 |
Change From Baseline in Insomnia Severity Index (ISI) Score
The ISI is a self-rated questionnaire assessing the difficulty over the past two weeks with falling to sleep, awakening in the middle of the night, and early morning awakening, as well as the degree to which insomnia impairs daily function. It included 5 items (rst item has 3 sub-questions), so a total of 7 questions. Each question is scored 0-4 (0=none, 1=mild, 2=moderate, 3=severe, 4=very severe). The total score is the sum of 7 item scores and ranged from 0: no symptoms to 28: severe symptoms. Higher score indicated worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01339689)
Timeframe: Baseline (Week 0) and Week 6
| Intervention | Scores on a scale (Mean) |
|---|
| Placebo | 17.04 |
| Ganaxolone | 14.36 |
Change From Baseline in Patient Health Questionnaire (PHQ-9) Score
The PHQ-9 is the nine-item depression scale of the Patient Health Questionnaire. The nine items of the PHQ-9 are based directly on the nine diagnostic criteria for major depressive disorder in the DSM-IV. Each item is scored 0-3 (0=not at all; 1=several days; 2=more than half the days; 3= nearly every day). The total score is the sum of 9 item scores and ranged 0: no depression to 27: severe depression. The higher the total score, the worse the depression. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01339689)
Timeframe: Baseline (Week 0) and Week 6
| Intervention | Scores on a scale (Mean) |
|---|
| Placebo | 12.13 |
| Ganaxolone | 10.71 |
Change From Baseline in Profile of Mood States (POMS) Total Score
The POMS is a factor-analytically derived 65 item self-report inventory with 5-point measures of five dimensions of negative mood: anger/irritability, anxiety/tension, depression/dejection, confusion/bewilderment, and fatigue/inertia, as well as vigor/activity. Total score was calculated as Fatigue + Mood (sum [Confusion, anger, Anxiety/Tension, Depression])- Vigor. Score ranged from 0: no symptoms to 200: severe symptoms; higher score indicated worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01339689)
Timeframe: Baseline (Week 0) and Week 6
| Intervention | Scores on a scale (Mean) |
|---|
| Placebo | 80.07 |
| Ganaxolone | 66.98 |
Change From Baseline in Clinician-Administered Posttrautamtic Stress Disorder (PTSD) Scale (CAPS) to Week 6
The CAPS was a structured interview that queries participants about each of the 17 Diagnostic and Statistical manual of Mental Disorders IV (DSM-IV) criteria B, C, and D symptoms of PTSD. Each item has a frequency score (0-4) and intensity score (0-4). The CAPS total score is the sum of frequency and intensity ratings for each item and the score range was 0: no symptoms to 136: severe symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01339689)
Timeframe: Baseline (Week 0) and at Week 2, Week 4 and Week 6
| Intervention | Scores on a scale (Mean) |
|---|
| Week 2 | Week 4 | Week 6 |
|---|
| Ganaxolone | 62.67 | 61.30 | 54.05 |
,| Placebo | 65.78 | 63.2 | 60.64 |
Change From Baseline in PTSD Avoidance Score
The CAPS was a structured interview that queries participants about each of the 17 Diagnostic and Statistical manual of Mental Disorders IV (DSM-IV) criteria B, C, and D symptoms of PTSD. Each item has a frequency score (0-4) and intensity score (0-4). The Avoidance score is the sum of frequency and intensity ratings for items from cluster C.and the score range was 0: no symptoms to 56: severe symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01339689)
Timeframe: Baseline (Week 0) and at Week 2, Week 4 and Week 6
| Intervention | Scores on a scale (Mean) |
|---|
| Week 2 | Week 4 | Week 6 |
|---|
| Ganaxolone | 26.29 | 26.09 | 23.52 |
,| Placebo | 27.06 | 25.87 | 24.82 |
Change From Baseline in PTSD Checklist (PCL) Scores
The PCL is a 17-item self-report scale representing all DSM-IV criteria for PTSD, including re-experiencing, avoidance and numbing, and hyperarousal criteria. Each item is scored 1-5 (1=not at all; 2=a little bit; 3=moderately; 4=quite a bit; 5=extremely). The total score is the sum of 17 item scores and ranged from 17: no symptoms to 85: severe symptoms. Higher score indicated worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01339689)
Timeframe: Baseline (Week 0) and at Week 2, Week 4 and Week 6
| Intervention | Scores on a scale (Mean) |
|---|
| Week 2 | Week 4 | Week 6 |
|---|
| Ganaxolone | 50.79 | 48.74 | 46.33 |
,| Placebo | 54.4 | 52.93 | 51.75 |
Change From Baseline in PTSD Hyperarousal Score
The CAPS was a structured interview that queries participants about each of the 17 Diagnostic and Statistical manual of Mental Disorders IV (DSM-IV) criteria B, C, and D symptoms of PTSD. Each item has a frequency score (0-4) and intensity score (0-4). The Hyperarousal score is the sum of frequency and intensity ratings for items from cluster D and the score range was 0: no symptoms to 40: severe symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01339689)
Timeframe: Baseline (Week 0) and at Week 2, Week 4 and Week 6
| Intervention | Scores on a scale (Mean) |
|---|
| Week 2 | Week 4 | Week 6 |
|---|
| Ganaxolone | 21.94 | 21.05 | 18.21 |
,| Placebo | 22.16 | 20.78 | 20.32 |
Change From Baseline in PTSD Re-Experience Score
The CAPS was a structured interview that queries participants about each of the 17 Diagnostic and Statistical manual of Mental Disorders IV (DSM-IV) criteria B, C, and D symptoms of PTSD. Each item has a frequency score (0-4) and intensity score (0-4). The Re-experience score is the sum of frequency and intensity ratings for items from cluster B and the score range was 0: no symptoms to 40: severe symptoms. Higher score indicates worse symptoms. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01339689)
Timeframe: Baseline (Week 0) and at Week 2, Week 4 and Week 6
| Intervention | Scores on a scale (Mean) |
|---|
| Week 2 | Week 4 | Week 6 |
|---|
| Ganaxolone | 14.45 | 14.16 | 12.31 |
,| Placebo | 16.56 | 16.54 | 15.5 |
Number of Participants With Response to CGI-I Subject Scale Clinical Global Impression - Improvement (Subject) (CGI-IS) Scale
The CGI-IS scale is a 7-point scale where the participant assesses how much the illness has improved or worsened relative to a Baseline state at the beginning of the intervention, and rated as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Higher score indicated worse symptoms. The score was grouped into two categories for analysis: Responders=1 or 2, Non-responders=3-7. (NCT01339689)
Timeframe: Week 2, Week 4 and Week 6
| Intervention | Participants (Count of Participants) |
|---|
| Week 2 - Non-Responder | Week 2 - Responder | Week 4 - Non-Responder | Week 4 - Responder | Week 6 - Non-Responder | Week 6 - Responder |
|---|
| Ganaxolone | 46 | 2 | 37 | 6 | 37 | 5 |
,| Placebo | 45 | 5 | 39 | 7 | 37 | 7 |
Clinical Global Impression-Improvement (CGI-I) Scale
"The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. very much improved; 2. much improved; 3. minimally improved; 4. no change; 5. minimally worse; 6. much worse; 7. very much worse. Higher scores indicated worse condition." (NCT01725152)
Timeframe: Week 14 (End of Treatment)
| Intervention | Scores on a scale (Least Squares Mean) |
|---|
| Ganaxolone | 3.4 |
| Placebo | 3.5 |
Pediatric Anxiety Rating Scale (PARS) Total Score
Pediatric Anxiety Rating Scale (PARS) is a clinician administered measure of anxiety in children and adolescents. The PARS is comprised of a 50-item symptom checklist used to determine the presence or absence of specific anxiety symptoms during the prior week and 7 severity/impairment items, each scored from 0 to 5. The score on the 7 items allows the clinician to rate symptom severity and associated impairment on a range from 0 to 35, with higher scores reflecting greater symptom severity and associated impairment. (NCT01725152)
Timeframe: Week 14 (End of Treatment)
| Intervention | Scores on a scale (Least Squares Mean) |
|---|
| Ganaxolone | 8.3 |
| Placebo | 9.2 |
Visual Analogue Scale (VAS)
"A semi-structured VAS design was employed, providing two of the three behaviors to be assessed as anxiety and attention, chosen by caregiver(s) of one additional behavior from a bank of five. This bank included sociability, attention, aggression, language, and hyperactivity/impulsivity. Parents mark on a visual line measuring 10 centimeters (cm) with worst behavior at 0 cm and best behavior at 10 cm. For each behavior the caregiver is instructed to mark their impression of behavior at Baseline visit and again at each visit. The calculated distance in cm between the baseline and each visit marks thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the least square mean distance and its corresponding standard error in cm from the worst behavior side, at baseline. Smaller the value, worser the behavior." (NCT01725152)
Timeframe: Week 14 (End of Treatment)
| Intervention | Centimeters (cm) (Least Squares Mean) |
|---|
| Severity of Anxiety | Severity of Attention | Severity of Target Behavior 3 |
|---|
| Ganaxolone | 5.6 | 4.4 | 4.4 |
,| Placebo | 5.0 | 3.9 | 3.9 |
Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV)
The SNAP-IV is a revision of the Swanson, Nolan, and Pelham (SNAP) Questionnaire. The SNAP-IV: ADHD Inattention Subscale (items 1-9) scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. The SNAP-IV ADHD Hyperactivity/Impulsivity Subscale (items 10-18) scores the intensity of each item in the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). Possible scores ranged from 0-27; higher scores indicated a greater intensity. SNAP-IV ADHD Combined Scale score (inattention + hyperactivity/impulsivity) ranged from 0-54. A low score of 0 indicates less inattention + hyperactivity/impulsivity. A high score of 54 indicates more inattention + hyperactivity. (NCT01725152)
Timeframe: Week 14 (End of Treatment)
| Intervention | Scores on a scale (Least Squares Mean) |
|---|
| ADHD Inattention | ADHD Hyperactivity/Impulsive | ADHD Combined |
|---|
| Ganaxolone | 15.5 | 13.9 | 29.3 |
,| Placebo | 14.6 | 12.6 | 27.1 |
Anxiety, Depression, and Mood Scale (ADAMS)
The ADAMS is a 28-item behavior-based informant instrument rated by the parent(s), legal authorized guardian(s), or consistent caregiver(s). The scale is composed of 5 factors, which addresses Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, and Obsessive/Compulsive Behavior. Items are scored on a 0-3 Likert scale that combines frequency and severity ratings (where 0=behavior has not occurred or is not a problem, 3=behavior occurs a lot or is a severe problem). Each subscale score is calculated separately; the scale range for Manic/Hyperactive Behavior is 0-15; for Depressed Mood, 0-21; for Social Avoidance, 0-21; for General Anxiety, 0-21; for Obsessive Behavior, 0-9. There is an overlapped item between Manic/Hypertension Behavior and General Anxiety; hence, the subscale ranges appear to reflect scores for 29 items instead of 28 items. (NCT01725152)
Timeframe: Week 14 (End of Treatment)
| Intervention | Scores on a scale (Least Squares Mean) |
|---|
| Manic/Hyperactive Behavior Total | Depress Mood Total | Social Avoidance Total | General Anxiety Total | Obsessive/Compulsive Behavior Total |
|---|
| Ganaxolone | 7.4 | 3.5 | 5.8 | 6.2 | 2.7 |
,| Placebo | 7.8 | 2.6 | 6.3 | 7.0 | 2.8 |
Aberrant Behavior Checklist (ABC)
The ABC is a 58-item parent rated from 0 (not at all a problem) to 3 (the problem is severe in degree with 6 subscales: Irritability (includes agitation, aggression, and self-injury, 15 items) with range of scores from 0-45; Social Withdrawal/Lethargy (16 items) with range of scores from 0-48; Stereotypy (7 items) with range of scores from 0-21; Hyperactivity (16 items) with range of scores from 0-48; Inappropriate Speech (4 items) with range of scores from 0-12 and Social avoidance (4 items) with range of scores from 0-12. Higher scores indicated greater severity. Social Withdrawal and Lethargy are reporting the same scale and Social Avoidance is a subscale of Social Withdrawal; hence, the subscale ranges appear to reflect scores for 62 items instead of 58 items. (NCT01725152)
Timeframe: Week 14 (End of Treatment)
| Intervention | Scores on a scale (Least Squares Mean) |
|---|
| Total - Subscale I (Irritability) | Total - Subscale II (Social Withdrawal/Lethargy) | Total - Subscale III - (Stereotypy) | Total - Subscale IV (Hyperactivity) | Total - Subscale V (Inappropriate Speech) | Total - Subscale VI (Social Avoidance) |
|---|
| Ganaxolone | 15.7 | 5.6 | 5.7 | 11.3 | 5.1 | 2.4 |
,| Placebo | 16.1 | 5.7 | 6.4 | 12.3 | 5.3 | 2.8 |
Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 2
To evaluate the effects of ganaxolone on ad lib smoking by looking at the percent change in expired air CO at the end of week two (relative to baseline). (NCT01857531)
Timeframe: Baseline and 2 Weeks
| Intervention | percentage change (Mean) |
|---|
| Ganaxolone -- Nicotine Patch | -0.52 |
Number of Participants Completing Continuous 6-week Abstinence From Smoking
Continuous six week abstinence from smoking at final study visit (approximately 6 weeks post quit date), based on self-reported abstinence confirmed by expired air CO (NCT01857531)
Timeframe: 6 Weeks post quit
| Intervention | participants (Number) |
|---|
| Ganaxolone -- Nicotine Patch | 4 |
Number of Participants Completing Abstinence From Smoking During the Last Four Weeks of Treatment
End of treatment abstinence from smoking during the last four weeks of treatment, based on self-reported abstinence during last four weeks confirmed by expired air CO (NCT01857531)
Timeframe: 4 Week abstinence from smoking at 6 weeks post quit
| Intervention | participants (Number) |
|---|
| Ganaxolone -- Nicotine Patch | 5 |
Number of Participants Completing Continuous 2-week Abstinence From Smoking
Continuous two week abstinence from smoking at the first post-quit visit (approximately 2 weeks post quit date), based on self-reported abstinence confirmed by expired air CO. (NCT01857531)
Timeframe: 2 Weeks post quit
| Intervention | participants (Number) |
|---|
| Ganaxolone -- Nicotine Patch | 3 |
Number of Participants Completing Point Abstinence From Smoking Two Weeks After Quitting
Point abstinence from smoking two weeks post quit, based on self-reported abstinence during last seven days confirmed by expired air CO at first post-quit visit. (NCT01857531)
Timeframe: 7 day point abstinence from smoking at 2 weeks post quit
| Intervention | participants (Number) |
|---|
| Ganaxolone -- Nicotine Patch | 4 |
Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 4
To evaluate the effects of ganaxolone as an augmentation treatment in conjunction with nicotine patch by looking at the percent change in expired air CO at the end of week four (relative to baseline). (NCT01857531)
Timeframe: Baseline and 4 Weeks
| Intervention | percentage change (Mean) |
|---|
| Ganaxolone -- Nicotine Patch | -39.40 |
Double Blind: Cohort 2: Percentage of Responders Experiencing a ≥R% (80%, 60%, 40%, and 20%) Reduction From Baseline to the End of Treatment Period in 28-day Seizure Frequency During Maintenance Period
Percentage of participants who had reductions of ≥ 80%, ≥ 60%, ≥ 40%, and ≥ 20% in 28-day seizure frequency from Baseline is presented. A responder is an individual whose reduction of percent change from Baseline in 28-day seizure frequency was ≥ 50%. Baseline was defined as non-missing value of last assessment before first dose. (NCT01963208)
Timeframe: Week 2 to Week 14
| Intervention | Percentage of participants (Number) |
|---|
| Reduction ≥ 80% | Reduction ≥ 60% | Reduction ≥ 40% | Reduction ≥ 20% |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 8.43 | 24.16 | 33.71 | 47.19 |
,| Double Blind: Cohort 2 - Placebo | 5.81 | 18.02 | 31.4 | 42.44 |
Double Blind: Cohort 2: Percentage of Responders Experiencing a ≥R% (80%, 60%, 40%, and 20%) Reduction From Baseline to the End of Treatment Period in 28-day Seizure Frequency During Titration + Maintenance Period
Percentage of participants who had reductions of ≥ 80%, ≥ 60%, ≥ 40%, and ≥ 20% in 28-day seizure frequency from Baseline is presented. A responder is an individual whose reduction of percent change from Baseline in 28-day seizure frequency was ≥ 50%. Baseline was defined as non-missing value of last assessment before first dose. (NCT01963208)
Timeframe: Up to Week 14
| Intervention | Percentage of participants (Number) |
|---|
| Reduction ≥ 80% | Reduction ≥ 60% | Reduction ≥ 40% | Reduction ≥ 20% |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 7.3 | 20.79 | 33.15 | 51.69 |
,| Double Blind: Cohort 2 - Placebo | 2.33 | 16.86 | 29.65 | 43.6 |
Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 8
"The CGI-I scale is a clinician-rated 7-point Likert scale used to assess the degree to which the participant's epilepsy symptoms have changed relative to Baseline. It was rated as 1. very much improved; 2. much improved; 3. minimally improved; 4. no change; 5. minimally worse; 6. much worse; 7. very much worse. Higher scores indicated worse condition. Baseline was defined as non-missing value of last assessment before first dose." (NCT01963208)
Timeframe: At Week 8
| Intervention | Participants (Count of Participants) |
|---|
| Very much improved | Much improved | Minimally improved | No change | Minimally worse | Much worse | Very much worse |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 3 | 27 | 50 | 68 | 8 | 9 | 1 |
,| Double Blind: Cohort 2 - Placebo | 4 | 20 | 49 | 71 | 12 | 5 | 1 |
Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 14
"The CGI-I scale is a clinician-rated 7-point Likert scale used to assess the degree to which the participant's epilepsy symptoms have changed relative to Baseline. It was rated as 1. very much improved; 2. much improved; 3. minimally improved; 4. no change; 5. minimally worse; 6. much worse; 7. very much worse. Higher scores indicated worse condition. Baseline was defined as non-missing value of last assessment before first dose." (NCT01963208)
Timeframe: At Week 14
| Intervention | Participants (Count of Participants) |
|---|
| Very much improved | Much improved | Minimally improved | No change | Minimally worse | Much worse | Very much worse |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 7 | 28 | 41 | 56 | 6 | 2 | 0 |
,| Double Blind: Cohort 2 - Placebo | 5 | 30 | 47 | 67 | 8 | 2 | 0 |
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Maintenance Period
Seizure frequency was based on the number of seizures per 28 days, calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period (≤ 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Baseline was defined as non-missing value of last assessment before first dose. (NCT01963208)
Timeframe: Baseline and Week 2 to Week 14
| Intervention | Percent change (Median) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | -20.56 |
| Double Blind: Cohort 2 - Placebo | -12.50 |
Double Blind: Cohort 2: Percentage of Seizure Free Participants During the Maintenance Period
Percentage of participants who completed the study without any seizures is presented (NCT01963208)
Timeframe: Week 2 to Week 14
| Intervention | Percentage of participants (Number) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 1.12 |
| Double Blind: Cohort 2 - Placebo | 0 |
Double Blind: Cohort 2: Percentage of Participants Who Experienced at Least One 28-day Seizure Free Period During Titration + Maintenance Phase
Percentage of participants who experienced at least one 28-day seizure free period is presented (NCT01963208)
Timeframe: Up to Week 14
| Intervention | Percentage of participants (Number) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 17.98 |
| Double Blind: Cohort 2 - Placebo | 18.02 |
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
Seizure frequency was based on the number of seizures per 28 days, calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period (≤ 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Baseline was defined as non-missing value of last assessment before first dose. Primary analysis was performed using a rank analysis of covariance (ANCOVA). (NCT01963208)
Timeframe: Baseline and Week 14
| Intervention | Percent change (Median) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | -21.28 |
| Double Blind: Cohort 2 - Placebo | -10.25 |
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency for Different Subtypes of Seizures During Titration + Maintenance Period
Seizure frequency was based on the number of seizures per 28 days, calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. The analysis was conducted for Partial-Onset Seizure (POS) only which included seizure subtypes: Complex partial seizures (CPS), secondarily generalized tonic-clonic (SGTC) seizures, simple partial seizure with motor/observable component (SPS-Motor) and Simple partial seizure (SPS) without motor/observable component. Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period (≤ 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Baseline was defined as non-missing value of last assessment before first dose. (NCT01963208)
Timeframe: Baseline and Week 14
| Intervention | Percent change (Mean) |
|---|
| CPS | SGTC | SPS-Motor | SPS |
|---|
| Double Blind: Cohort 2 - Ganaxolone | -4.70 | -27.42 | -5.52 | 12.57 |
,| Double Blind: Cohort 2 - Placebo | -6.52 | 1.02 | -21.97 | -3.53 |
Double Blind: Cohort 2: Number of Participants With Patient Global Impression of Change - Improvement (PGI-I) at Week 8 and Week 14
"The PGI-I scale was a 7-point Likert scale completed by the Patient or Caregiver representing the degree to which the participant's epilepsy symptoms had changed relative to Baseline. It was rated as 1. very much improved; 2. much improved; 3. minimally improved; 4. no change; 5. minimally worse; 6. much worse; 7. very much worse. Higher score indicated worse condition. Baseline was defined as non-missing value of last assessment before first dose." (NCT01963208)
Timeframe: Week 8 and Week 14
| Intervention | Participants (Count of Participants) |
|---|
| Week 8: Very Much Improved | Week 8: Much Improved | Week 8: Minimally Improved | Week 8: No Change | Week 8: Minimally Worse | Week 8: Much Worse | Week 8: Very Much Worse | Week 14: Very Much Improved | Week 14: Much Improved | Week 14: Minimally Improved | Week 14: No Change | Week 14: Minimally Worse | Week 14: Much Worse | Week 14: Very Much Worse |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 7 | 30 | 44 | 59 | 12 | 8 | 6 | 7 | 33 | 43 | 46 | 7 | 3 | 1 |
,| Double Blind: Cohort 2 - Placebo | 5 | 21 | 51 | 65 | 11 | 4 | 4 | 10 | 29 | 43 | 60 | 12 | 4 | 1 |
Double Blind: Cohort 2: Longest Percent of Time Spent Seizure-free During Titration + Maintenance Period
The longest period of time seizure-free was defined as the percent of the longest seizure-free period (days) divided by the days with available seizure data, and then multiplied by 100%. (NCT01963208)
Timeframe: Up to Week 14
| Intervention | Percentage of time spent (Mean) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 24.00 |
| Double Blind: Cohort 2 - Placebo | 17.58 |
Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Titration + Maintenance Period
Baseline number of seizure free days per 28-day period was calculated as: the number of seizure free days in the entire Baseline period (<=56 days) divided by the number of days with available seizure data in the baseline period and multiplied by 28. Post-Baseline number of seizure free days per 28-day period was calculated as: the number of seizure free days in the entire treatment period divided by the number of days with available seizure data in the treatment period and multiplied by 28. Change from Baseline in number of seizure free days per 28-day period from Baseline was calculated as: Post-Baseline number of seizure free days per 28-day period minus Baseline number of seizure free days per 28-day period. Baseline was defined as non-missing value of last assessment before first dose. (NCT01963208)
Timeframe: Baseline and Week 14
| Intervention | Seizure free days (Mean) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 1.47 |
| Double Blind: Cohort 2 - Placebo | 1.01 |
Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Maintenance Period
Baseline number of seizure free days per 28-day period was calculated as: the number of seizure free days in the entire Baseline period (≤ 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Post-Baseline number of seizure free days per 28-day period was calculated as: the number of seizure free days in the entire treatment period divided by the number of days with available seizure data in the treatment period and multiplied by 28. Change from Baseline in number of seizure free days per 28-day period from Baseline was calculated as: Post-Baseline number of seizure free days per 28-day period minus Baseline number of seizure free days per 28-day period. Baseline was defined as non-missing value of last assessment before first dose. (NCT01963208)
Timeframe: Baseline and Week 2 to Week 14
| Intervention | Seizure free days (Mean) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 1.63 |
| Double Blind: Cohort 2 - Placebo | 1.20 |
Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
Seizure frequency was based on the number of seizures per 28 days, calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period (≤ 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Baseline was defined as non-missing value of last assessment before first dose. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01963208)
Timeframe: Baseline and Week 14
| Intervention | Seizures per 28 days (Mean) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | -1.46 |
| Double Blind: Cohort 2 - Placebo | -0.33 |
Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Maintenance Period
Seizure frequency was based on the number of seizures per 28 days, calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period (≤ 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Baseline was defined as non-missing value of last assessment before first dose. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT01963208)
Timeframe: Baseline and Week 2 to Week 14
| Intervention | Seizures per 28 days (Mean) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | -1.67 |
| Double Blind: Cohort 2 - Placebo | -0.64 |
Double Blind: Cohort 2: Number of Participants With ≥50% Responder Rate During Titration + Maintenance Period
A 50% responder was a participant who experienced at least a 50% decrease in 28-day seizure frequency compared to Baseline. (NCT01963208)
Timeframe: Up to Week 14
| Intervention | Participants (Count of Participants) |
|---|
| Double Blind: Cohort 2 - Ganaxolone | 50 |
| Double Blind: Cohort 2 - Placebo | 39 |
Summary of CGII-P
Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ] CGII-P scale is qualitative values and not quantitative. (NCT02358538)
Timeframe: Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ]
| Intervention | Participants (Count of Participants) |
|---|
| Visit 4 (End of Week 4) - Very Much Improved | Visit 4 (End of Week 4) - Much Improved | Visit 4 (End of Week 4) - Minimally Improved | Visit 4 (End of Week 4) - No Change | Visit 4 (End of Week 4) - Minimally Worse | Visit 4 (End of Week 4) - Much Worse | Visit 4 (End of Week 4) - Very Much Worse | Visit 5 (End of Week 8) - Very Much Improved | Visit 5 (End of Week 8) - Much Improved | Visit 5 (End of Week 8) - Minimally Improved | Visit 5 (End of Week 8) - No Change | Visit 5 (End of Week 8) - Minimally Worse | Visit 5 (End of Week 8) - Much Worse | Visit 5 (End of Week 8) - Very Much Worse | Visit 6 (End of Week 17) - Very Much Improved | Visit 6 (End of Week 17) - Much Improved | Visit 6 (End of Week 17) - Minimally Improved | Visit 6 (End of Week 17) - No Change | Visit 6 (End of Week 17) - Minimally Worse | Visit 6 (End of Week 17) - Much Worse | Visit 6 (End of Week 17) - Very Much Worse | Visit 7 (End of Week 26) - Very Much Improved | Visit 7 (End of Week 26) - Much Improved | Visit 7 (End of Week 26) - Minimally Improved | Visit 7 (End of Week 26) - No Change | Visit 7 (End of Week 26) - Minimally Worse | Visit 7 (End of Week 26) - Much Worse | Visit 7 (End of Week 26) - Very Much Worse | Visit 8 (End of Week 44) - Very Much Improved | Visit 8 (End of Week 44) - Much Improved | Visit 8 (End of Week 44) - Minimally Improved | Visit 8 (End of Week 44) - No Change | Visit 8 (End of Week 44) - Minimally Worse | Visit 8 (End of Week 44) - Much Worse | Visit 8 (End of Week 44)- Very Much Worse | Visit 9 (End of Week 62) - Very Much Improved | Visit 9 (End of Week 62) - Much Improved | Visit 9 (End of Week 62)- Minimally Improved | Visit 9 (End of Week 62) - No Change | Visit 9 (End of Week 62) - Minimally Worse | Visit 9 (End of Week 62) - Much Worse | Visit 9 (End of Week 62) - Very Much Worse | Visit 10 (End of Week 78) - Very Much Improved | Visit 10 (End of Week 78) - Much Improved | Visit 10 (End of Week 78)- Minimally Improved | Visit 10 (End of Week 78) - No Change | Visit 10 (End of Week 78) - Minimally Worse | Visit 10 (End of Week 78) - Much Worse | Visit 10 (End of Week 78) - Very Much Worse |
|---|
| CDKL5 | 0 | 1 | 4 | 2 | 0 | 0 | 0 | 0 | 1 | 5 | 0 | 1 | 0 | 0 | 1 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 1 | 1 | 1 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 |
,| CSWS | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
,| Lennox-Gastaut | 3 | 2 | 3 | 0 | 0 | 0 | 0 | 2 | 2 | 3 | 1 | 0 | 0 | 0 | 1 | 1 | 3 | 0 | 1 | 0 | 0 | 1 | 1 | 3 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
,| PCDH19 | 1 | 2 | 5 | 3 | 0 | 0 | 0 | 0 | 2 | 2 | 1 | 1 | 1 | 0 | 1 | 1 | 4 | 0 | 0 | 0 | 0 | 2 | 2 | 3 | 0 | 1 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 1 | 0 |
Summary of CGII-C
Clinician Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ] CGII-C scale is qualitative values and not quantitative. (NCT02358538)
Timeframe: End of Week 4, End of Week 8, End of Week 17, End of Week 26, Week 44, Week 62, Week 78
| Intervention | Participants (Count of Participants) |
|---|
| Visit 4 (End of Week 4) - Very Much Improved | Visit 4 (End of Week 4) - Much Improved | Visit 4 (End of Week 4) - Minimally Improved | Visit 4 (End of Week 4) - No Change | Visit 4 (End of Week 4) - Minimally Worse | Visit 4 (End of Week 4) - Much Worse | Visit 4 (End of Week 4) - Very Much Worse | Visit 5 (End of Week 8) - Very Much Improved | Visit 5 (End of Week 8) - Much Improved | Visit 5 (End of Week 8) - Minimally Improved | Visit 5 (End of Week 8) - No Change | Visit 5 (End of Week 8) - Minimally Worse | Visit 5 (End of Week 8) - Much Worse | Visit 5 (End of Week 8) - Very Much Worse | Visit 6 (End of Week 17) - Very Much Improved | Visit 6 (End of Week 17) - Much Improved | Visit 6 (End of Week 17) - Minimally Improved | Visit 6 (End of Week 17) - No Change | Visit 6 (End of Week 17) - Minimally Worse | Visit 6 (End of Week 17) - Much Worse | Visit 6 (End of Week 17) - Very Much Worse | Visit 7 (End of Week 26) - Very Much Improved | Visit 7 (End of Week 26) - Much Improved | Visit 7 (End of Week 26) - Minimally Improved | Visit 7 (End of Week 26) - No Change | Visit 7 (End of Week 26) - Minimally Worse | Visit 7 (End of Week 26) - Much Worse | Visit 7 (End of Week 26) - Very Much Worse | Visit 8 (End of Week 44) - Very Much Improved | Visit 8 (End of Week 44) - Much Improved | Visit 8 (End of Week 44) - Minimally Improved | Visit 8 (End of Week 44) - No Change | Visit 8 (End of Week 44) - Minimally Worse | Visit 8 (End of Week 44) - Much Worse | Visit 8 (End of Week 44) - Very Much Worse | Visit 9 (End of Week 62) - Very Much Improved | Visit 9 (End of Week 62) - Much Improved | Visit 9 (End of Week 62) - Minimally Improved | Visit 9 (End of Week 62) - No Change | Visit 9 (End of Week 62) - Minimally Worse | Visit 9 (End of Week 62) - Much Worse | Visit 9 (End of Week 62) - Very Much Worse | Visit 10 (End of Week 78) - Very Much Improved | Visit 10 (End of Week 78) - Much Improved | Visit 10 (End of Week 78) - Minimally Improved | Visit 10 (End of Week 78) - No Change | Visit 10 (End of Week 78) - Minimally Worse | Visit 10 (End of Week 78) - Much Worse | Visit 10 (End of Week 78) - Very Much Worse |
|---|
| CDKL5 | 0 | 3 | 2 | 2 | 0 | 0 | 0 | 0 | 4 | 2 | 1 | 0 | 0 | 0 | 1 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 2 | 0 | 1 | 0 | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
,| CSWS | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
,| Lennox-Gastaut | 2 | 4 | 2 | 0 | 0 | 0 | 0 | 1 | 4 | 2 | 1 | 0 | 0 | 0 | 2 | 3 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
,| PCDH19 | 1 | 4 | 3 | 3 | 0 | 0 | 0 | 0 | 2 | 2 | 1 | 2 | 0 | 0 | 1 | 1 | 4 | 0 | 0 | 0 | 0 | 2 | 2 | 2 | 2 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 1 | 0 |
Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters for 52-week OLE Period (Mean Percent Change & Standard Deviation)
Percentage change from baseline in 28-day seizure frequency at 3 months (day 91), 26 weeks, 52 week OLE (Mean Percent Change & Standard Deviation) (NCT02358538)
Timeframe: Baseline through 52 week open label period
| Intervention | percentage of change of frequency (Mean) |
|---|
| Percent Change from baseline (at day 91) | Percent Change from baseline (at week 26) | Percent change from baseline (52 week OLE through month 6) | Percent change from baseline (52 week OLE period) |
|---|
| CDKL5 | -31.23 | -20.55 | -54.41 | -49.20 |
,| CSWS | NA | NA | NA | NA |
,| Lennox- Gastaut | 122.10 | 125.38 | -38.74 | -37.75 |
,| PCDH19 | 52.83 | 46.36 | -19.98 | -19.95 |
Number of Participants With Responder Rate of Seizure Frequency
Responder Rate in Terms of 28-day Seizure Frequency Based on the Sum of Individual Seizures and Clusters (NCT02358538)
Timeframe: Month 3 and Week 26
| Intervention | Participants (Count of Participants) |
|---|
| Post-baseline through Month 3 (Day 91) - 25% Responder | Post-baseline through Month 3 (Day 91) - 50% Responder | Post-baseline through Month 3 (Day 91) - 75% Responder | Post-baseline 26-week open-label Period - 25% Responder | Post-baseline 26-week open-label Period - 50% Responder | Post-baseline 26-week open-label Period - 75% Responder |
|---|
| CDKL5 | 4 | 3 | 1 | 4 | 2 | 1 |
,| CSWS | NA | NA | NA | NA | NA | NA |
,| Lennox-Gastaut | 4 | 2 | 0 | 3 | 1 | 0 |
,| PCDH19 | 6 | 4 | 1 | 5 | 3 | 1 |
Mean Percentage Change of Individual Seizure-free Days
Mean Percentage Change of Individual Seizure-free days per 28-day period (through 52-week OLE) period relative to baseline (NCT02358538)
Timeframe: Baseline, Day 91, Week 26, 52-week OLE through month 6, 52-week OLE Period
| Intervention | Percentage Change (Mean) |
|---|
| Mean Percentage Change of individual seizure-free days from baseline to Day 91 | Mean Percentage Change of individual seizure-free days from baseline to Week 26 | Mean Percentage Change of individual seizure-free days from baseline to 52-week OLE (181 days) | Mean Percentage Change of individual seizure-free days from baseline to 52-week OLE Period |
|---|
| CDKL5 | 11.84 | 11.80 | 21 | 20.44 |
,| CSWS | NA | NA | NA | NA |
,| Lennox-Gastaut | -1.12 | -2.13 | 16.35 | 14.95 |
,| PCDH19 | 7.87 | 7.94 | 17.12 | 17.02 |
Number of Participants Who Showed Greater Than or Equal to 50% Reduction in 28-day Seizure Frequent From Baseline
A 50% responder is an individual whose reduction of percent change from Baseline to the end of the open label extension period in 28-day partial-onset seizure (POS) seizure frequency is greater than or equal to 50%. (NCT02519439)
Timeframe: Baseline and at Day 28
| Intervention | Participants (Count of Participants) |
|---|
| Ganaxolone | 14 |
Percent Change From Baseline in 28-day Seizure Frequency
Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period of Study 1042-0603 (less than or equal to 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Post-baseline 28-day seizure frequency was calculated as the number of seizures in the entire treatment period divided by the number of days with available seizure data in the treatment period and multiplied by 28. Baseline was defined as the last non-missing value obtained before the first treatment in the preceding Study 1042-0603. The calculation for percent change from Baseline in 28-day seizure frequency was done as follows for each participant: post-Baseline 28-day seizure frequency minus Baseline 28-day seizure frequency whole divided by Baseline 28-day seizure frequency multiplied by 100 percent. (NCT02519439)
Timeframe: Baseline and at Day 28
| Intervention | Percent change (Mean) |
|---|
| Ganaxolone | -41.86 |
Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores
"The participant is asked to rate the total improvement of their partial-onset seizures whether or not in the participant's judgment it is due entirely to drug treatment based on a 7-point scale using the markers very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse (1 = very much improved; 7 = very much worse). Higher scores indicated worse condition. Participants who showed PGI improvement at Week 104 (End of treatment) has been presented." (NCT02519439)
Timeframe: At Week 104
| Intervention | Participants (Count of Participants) |
|---|
| Very much improved | Much improved | Minimally improved | No change | Minimally worse | Much worse | Very much worse |
|---|
| Ganaxolone | 4 | 8 | 10 | 1 | 0 | 0 | 0 |
Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores
"The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. very much improved 2. much improved 3. minimally improved 4. no change 5. minimally worse 6. much worse 7. very much worse. Higher scores indicated worse condition. Participants who showed CGI improvement at Week 104 (End of treatment) has been presented." (NCT02519439)
Timeframe: At Week 104
| Intervention | Participants (Count of Participants) |
|---|
| Very much improved | Much improved | Minimally improved | No change | Minimally worse | Much worse | Very much worse |
|---|
| Ganaxolone | 1 | 9 | 11 | 2 | 0 | 0 | 0 |
Montgomery-Asberg Depression Rating Scale (MADRS)
The MADRS is a diagnostic questionnaire that is used to measure the severity of depressive episodes in patients with mood disorders. The minimum and maximum values are 0 and 60, respectively, (higher scores are more severe). (NCT02900092)
Timeframe: Week 8
| Intervention | units on a scale (Mean) |
|---|
| Ganaxolone Treatment Arm | 12.8 |
Change From Baseline in Spielberger State-Trait Anxiety Inventory 6-item Version (STAI6) Total Score
"The STAI6 is a 6-item self-rated instrument used to assess anxiety state. The STAI6 questions included: 1. I feel calm; 2. I am tense; 3. I feel upset; 4. I am relaxed; 5. I feel content; 6. I am worried. Each of these questions were rated as: a) not at all; b) somewhat; c) moderately; d) very much. For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. The STAI6 score was the result of first totaling the 6 individual item scores, and then prorating by a multiplication factor of 20/6 to acquire a score range of 20 (low anxiety) to 80 (high anxiety). Higher score indicated higher level of anxiety. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value." (NCT03228394)
Timeframe: Baseline, Day 1 (12 hours post start of infusion), Day 2, Day 3 post-infusion (60 hours post start of infusion), Day 4, Day 8, Day 11, Day 15, Day 22, Day 29, Day 34, Day 36, Day 57 and Day 71
| Intervention | Scores on a scale (Mean) |
|---|
| Day 1 (12 hours post start of infusion) | Day 2 | Day 8 | Day 15 | Day 22 | Day 29 | Day 36 | Day 57 | Day 71 |
|---|
| Ganaxolone Cohort 6 | -17.7 | -19.0 | -15.6 | -17.4 | -21.8 | -18.9 | -21.7 | -13.3 | -21.0 |
,| Placebo Cohort 6 | -9.4 | -12.9 | -10.2 | -12.3 | -15.9 | -20.8 | -21.9 | -21.7 | -31.7 |
Change From Baseline in Spielberger State-Trait Anxiety Inventory 6-item Version (STAI6) Total Score
"The STAI6 is a 6-item self-rated instrument used to assess anxiety state. The STAI6 questions included: 1. I feel calm; 2. I am tense; 3. I feel upset; 4. I am relaxed; 5. I feel content; 6. I am worried. Each of these questions were rated as: a) not at all; b) somewhat; c) moderately; d) very much. For questions 2, 3, and 6, the scoring was a = 1, b = 2, c = 3, and d = 4. For the other 3 questions, the scoring was a = 4, b = 3, c = 2, and d = 1. The STAI6 score was the result of first totaling the 6 individual item scores, and then prorating by a multiplication factor of 20/6 to acquire a score range of 20 (low anxiety) to 80 (high anxiety). Higher score indicated higher level of anxiety. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value." (NCT03228394)
Timeframe: Baseline, Day 1 (12 hours post start of infusion), Day 2, Day 3 post-infusion (60 hours post start of infusion), Day 4, Day 8, Day 11, Day 15, Day 22, Day 29, Day 34, Day 36, Day 57 and Day 71
| Intervention | Scores on a scale (Mean) |
|---|
| Day 1 (12 hours post start of infusion) | Day 2 | Day 3 post-infusion (60 hours post start of infusion) | Day 4 | Day 11 | Day 34 |
|---|
| Ganaxolone Cohort 1 | -4.2 | -8.7 | -22.0 | -20.7 | -18.7 | -16.0 |
,| Ganaxolone Cohort 2 | -12.01 | -14.2 | -21.0 | -22.9 | -20.8 | -24.4 |
,| Ganaxolone Cohort 3 | -11.3 | -12.0 | -24.0 | -22.3 | -16.0 | -17.7 |
,| Placebo Cohort 3 | -10.7 | -12.7 | -24.3 | -25.0 | -17.0 | -18.7 |
,| Placebo Cohort 1 | -8.9 | -9.2 | -11.7 | -20.0 | -21.7 | -20.8 |
,| Placebo Cohort 2 | -14.5 | -15.0 | -18.2 | -21.0 | -16.9 | -16.1 |
Number of Participants With HAMD17 Remission
HAMD17 Remission was defined as total score ≤7. The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Number of participants with HAMD17 remission is presented (NCT03228394)
Timeframe: Day1 post-infusion (6 hours post start of infusion [SOI]), Day 1 (12 hours post SOI), Day2 (24 hours post SOI), Day 3 post-infusion (48 hours post SOI), Day 3 post-infusion (60 hours post SOI), Day 4 (72 hours post SOI), Days 8,11,15,22,29,34,57 and 71
| Intervention | Participants (Count of Participants) |
|---|
| Day 1 (12 hours post start of infusion): Remission | Day 2 (24 hours post start of infusion): Remission | Day 3 post-infusion (48 hours post start of infusion): Remission | Day 3 post-infusion (60 hours post start of infusion): Remission | Day 4 (72 hours post start of infusion): Remission | Day 11: Remission | Day 34: Remission |
|---|
| Ganaxolone Cohort 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 |
,| Ganaxolone Cohort 2 | 0 | 1 | 3 | 4 | 7 | 5 | 5 |
,| Ganaxolone Cohort 3 | 0 | 0 | 2 | 2 | 3 | 1 | 4 |
,| Placebo Cohort 1 | 0 | 0 | 1 | 1 | 2 | 1 | 3 |
,| Placebo Cohort 2 | 0 | 0 | 3 | 4 | 4 | 3 | 4 |
,| Placebo Cohort 3 | 0 | 1 | 1 | 2 | 3 | 2 | 2 |
Change From Baseline in HAMD17 Total Score at Indicated Time Points
The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT03228394)
Timeframe: Baseline, Day1 post-infusion(6hours post start of infusion), Day1(12hours post start of infusion), Day2(24hours post start of infusion),Day3 post-infusion(48hours post start of infusion),Day4(72hours post start of infusion),Days 8,11,15,22,36,57 and 71
| Intervention | Scores on a scale (Mean) |
|---|
| Day 1 (12 hours post start of infusion) | Day 2 (24 hours post start of infusion) | Day 3 post-infusion (48 hours post start of infusion) | Day 4 (72 hours post start of infusion) | Day 11 | Day 36 |
|---|
| Ganaxolone Cohort 1 | -2.4 | -3.8 | -11.0 | -10.2 | -6.2 | -11.0 |
,| Ganaxolone Cohort 2 | -2.7 | -10.1 | -13.7 | -17.3 | -14.0 | -16.5 |
,| Ganaxolone Cohort 3 | 0.3 | -3.4 | -11.2 | -10.5 | -8.9 | -11.1 |
,| Placebo Cohort 1 | -3.8 | -8.0 | -10.8 | -12.8 | -13.3 | -17.0 |
,| Placebo Cohort 2 | -3.2 | -6.4 | -10.5 | -14.5 | -9.7 | -13.3 |
,| Placebo Cohort 3 | -1.9 | -5.2 | -8.7 | -14.0 | -8.2 | -9.1 |
Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Total Score
The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT03228394)
Timeframe: Baseline and Day 3 post-infusion (60 hours post start of infusion) for Cohorts 1 to 3 and Baseline and Day 29 for Cohort 6
| Intervention | Scores on a scale (Mean) |
|---|
| Day 3 post-infusion (60 hours post start of infusion) |
|---|
| Ganaxolone Cohort 1 | -12.0 |
,| Ganaxolone Cohort 2 | -14.3 |
,| Ganaxolone Cohort 3 | -11.3 |
,| Placebo Cohort 1 | -13.0 |
,| Placebo Cohort 2 | -14.0 |
,| Placebo Cohort 3 | -11.0 |
Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Total Score
The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT03228394)
Timeframe: Baseline and Day 3 post-infusion (60 hours post start of infusion) for Cohorts 1 to 3 and Baseline and Day 29 for Cohort 6
| Intervention | Scores on a scale (Mean) |
|---|
| Day 29 |
|---|
| Ganaxolone Cohort 6 | -11.5 |
,| Placebo Cohort 6 | -13.6 |
Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score
The EPDS is a validated 10-question depression assessment for postpartum women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression common in the postpartum period, such as changes in sleeping patterns. It consists of 10 multiple choice questions with scores for each question ranging from 0-3. Questions 1, 2, & 4 are scored 0, 1, 2 or 3 with top box scored as 0 and the bottom box scored as 3. Questions 3 and 5 to 10 are reverse scored, with the top box scored as a 3 and the bottom box scored as 0. Scores are then summed for a total score, which ranges from 0: no depression to 30: severe depression. Higher score indicates severe depression. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT03228394)
Timeframe: Baseline, Day 1, Day 2, Day 3 post-infusion (60 hours post start of infusion), Day 8, Day 11, Day 15, Day 22, Day 29, Day 34, Day 36, Day 57 and Day 71
| Intervention | Scores on a scale (Mean) |
|---|
| Day 3 post-infusion (60 hours post start of infusion) | Day 11 | Day 34 |
|---|
| Ganaxolone Cohort 1 | -8.0 | -8.0 | -8.6 |
,| Ganaxolone Cohort 2 | -10.8 | -11.5 | -13.4 |
,| Ganaxolone Cohort 3 | -10.9 | -8.2 | -8.8 |
,| Placebo Cohort 1 | -8.8 | -13.5 | -14.5 |
,| Placebo Cohort 2 | -10.8 | -9.6 | -9.8 |
,| Placebo Cohort 3 | -12.2 | -8.8 | -9.1 |
Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score
The EPDS is a validated 10-question depression assessment for postpartum women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression common in the postpartum period, such as changes in sleeping patterns. It consists of 10 multiple choice questions with scores for each question ranging from 0-3. Questions 1, 2, & 4 are scored 0, 1, 2 or 3 with top box scored as 0 and the bottom box scored as 3. Questions 3 and 5 to 10 are reverse scored, with the top box scored as a 3 and the bottom box scored as 0. Scores are then summed for a total score, which ranges from 0: no depression to 30: severe depression. Higher score indicates severe depression. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT03228394)
Timeframe: Baseline, Day 1, Day 2, Day 3 post-infusion (60 hours post start of infusion), Day 8, Day 11, Day 15, Day 22, Day 29, Day 34, Day 36, Day 57 and Day 71
| Intervention | Scores on a scale (Mean) |
|---|
| Day 1 | Day 2 | Day 8 | Day 15 | Day 22 | Day 29 | Day 36 | Day 57 | Day 71 |
|---|
| Ganaxolone Cohort 6 | -5.4 | -7.5 | -9.6 | -11.3 | -11.2 | -10.0 | -12.4 | -9.4 | -11.5 |
,| Placebo Cohort 6 | -1.9 | -4.9 | -6.7 | -8.0 | -8.2 | -10.9 | -11.8 | -11.8 | -14.0 |
Change From Baseline in HAMD17 Total Score at Indicated Time Points
The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. (NCT03228394)
Timeframe: Baseline, Day1 post-infusion(6hours post start of infusion), Day1(12hours post start of infusion), Day2(24hours post start of infusion),Day3 post-infusion(48hours post start of infusion),Day4(72hours post start of infusion),Days 8,11,15,22,36,57 and 71
| Intervention | Scores on a scale (Mean) |
|---|
| Day 1 post-infusion (6 hours post start of infusion) | Day 2 (24 hours post start of infusion) | Day 4 (72 hours post start of infusion) | Day 8 | Day 11 | Day 15 | Day 22 | Day 36 | Day 57 | Day 71 |
|---|
| Ganaxolone Cohort 6 | -6.1 | -7.8 | -7.0 | -8.7 | -13.6 | -12.7 | -12.7 | -13.0 | -12.0 | -14.8 |
,| Placebo Cohort 6 | -3.2 | -5.1 | -7.8 | -8.7 | -13.6 | -11.6 | -12.3 | -13.5 | -16.0 | -19.0 |
Number of Participants With HAMD17 Remission
HAMD17 Remission was defined as total score ≤7. The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Number of participants with HAMD17 remission is presented (NCT03228394)
Timeframe: Day1 post-infusion (6 hours post start of infusion [SOI]), Day 1 (12 hours post SOI), Day2 (24 hours post SOI), Day 3 post-infusion (48 hours post SOI), Day 3 post-infusion (60 hours post SOI), Day 4 (72 hours post SOI), Days 8,11,15,22,29,34,57 and 71
| Intervention | Participants (Count of Participants) |
|---|
| Day 1 post-infusion (6 hours post start of infusion): Remission | Day 2 (24 hours post start of infusion): Remission | Day 4 (72 hours post start of infusion): Remission | Day 8: Remission | Day 11: Remission | Day 15: Remission | Day 22: Remission | Day 29: Remission | Day 34: Remission | Day 57: Remission | Day 71: Remission |
|---|
| Ganaxolone Cohort 6 | 3 | 1 | 0 | 3 | 3 | 3 | 5 | 4 | 4 | 4 | 6 |
,| Placebo Cohort 6 | 0 | 0 | 2 | 2 | 4 | 4 | 4 | 6 | 5 | 6 | 7 |
Number of Participants With HAMD17 Response
HAMD17 Response was defined as ≥50% reduction from Baseline in total score. The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Number of participants with HAMD17 response is presented. (NCT03228394)
Timeframe: Day1 post-infusion (6 hours post start of infusion [SOI]), Day 1 (12 hours post SOI), Day 2 (24 hours post SOI),Day 3 post-infusion (48 hours post SOI), Day 3 post-infusion (60 hours post SOI), Day 4 (72 hours post SOI), Days 8,11,15,22,29,36,57 and 71
| Intervention | Participants (Count of Participants) |
|---|
| Day 1 post-infusion (6 hours post start of infusion): Responder | Day 2 (24 hours post start of infusion): Responder | Day 4 (72 hours post start of infusion): Responder | Day 8: Responder | Day 11: Responder | Day 15: Responder | Day 22: Responder | Day 29: Responder | Day 36: Responder | Day 57: Responder | Day 71: Responder |
|---|
| Ganaxolone Cohort 6 | 5 | 6 | 3 | 5 | 6 | 6 | 8 | 7 | 8 | 6 | 9 |
,| Placebo Cohort 6 | 2 | 1 | 3 | 4 | 6 | 8 | 7 | 8 | 6 | 8 | 9 |
Number of Participants With HAMD17 Response
HAMD17 Response was defined as ≥50% reduction from Baseline in total score. The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Number of participants with HAMD17 response is presented. (NCT03228394)
Timeframe: Day1 post-infusion (6 hours post start of infusion [SOI]), Day 1 (12 hours post SOI), Day 2 (24 hours post SOI),Day 3 post-infusion (48 hours post SOI), Day 3 post-infusion (60 hours post SOI), Day 4 (72 hours post SOI), Days 8,11,15,22,29,36,57 and 71
| Intervention | Participants (Count of Participants) |
|---|
| Day 1 (12 hours post start of infusion): Responder | Day 2 (24 hours post start of infusion): Responder | Day 3 post-infusion (48 hours post start of infusion): Responder | Day 3 post-infusion (60 hours post start of infusion): Responder | Day 4 (72 hours post start of infusion): Responder | Day 11: Responder | Day 36: Responder |
|---|
| Ganaxolone Cohort 1 | 0 | 0 | 1 | 2 | 3 | 1 | 3 |
,| Ganaxolone Cohort 2 | 0 | 4 | 7 | 7 | 11 | 5 | 7 |
,| Ganaxolone Cohort 3 | 0 | 0 | 4 | 5 | 5 | 3 | 5 |
,| Placebo Cohort 1 | 0 | 1 | 2 | 2 | 2 | 2 | 3 |
,| Placebo Cohort 2 | 1 | 4 | 6 | 7 | 7 | 5 | 5 |
,| Placebo Cohort 3 | 0 | 2 | 4 | 3 | 6 | 3 | 4 |
Number of Participants With Response to Clinical Global Impression-Improvement (CGI-I) Scale
"The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. very much improved; 2. much improved; 3. minimally improved; 4. no change; 5. minimally worse; 6. much worse; 7. very much worse. Higher scores indicated worse condition. Response was defined as >50% decrease from Baseline in CGI-I total score." (NCT03228394)
Timeframe: Day 1 (12 hours post start of infusion), Day 2, Day 3 post-infusion (60 hours post start of infusion), Day 4, Day 8, Day 11, Day 15, Day 22, Day 29, Day 34, Day 36, Day 57 and Day 71
| Intervention | Participants (Count of Participants) |
|---|
| Day 1 (12 hours post start of infusion): Very much or much improved | Day 1 (12 hours post start of infusion): Minimally or not improved | Day 2: Very much or much improved | Day 2: Minimally or not improved | Day 3 post-infusion (60 hours post start of infusion): Very much or much improved | Day 3 post-infusion (60 hours post start of infusion): Minimally or not improved | Day 4: Very much or much improved | Day 4: Minimally or not improved | Day 11: Very much or much improved | Day 11: Minimally or not improved | Day 34: Very much or much improved | Day 34: Minimally or not improved |
|---|
| Ganaxolone Cohort 1 | 0 | 5 | 1 | 4 | 4 | 1 | 3 | 2 | 0 | 5 | 3 | 2 |
,| Ganaxolone Cohort 2 | 3 | 12 | 8 | 7 | 9 | 4 | 12 | 3 | 9 | 4 | 8 | 4 |
,| Ganaxolone Cohort 3 | 0 | 10 | 3 | 7 | 7 | 3 | 7 | 3 | 5 | 5 | 5 | 5 |
,| Placebo Cohort 1 | 0 | 4 | 1 | 3 | 3 | 1 | 3 | 1 | 2 | 2 | 3 | 1 |
,| Placebo Cohort 2 | 2 | 12 | 3 | 10 | 7 | 6 | 6 | 7 | 7 | 5 | 5 | 7 |
,| Placebo Cohort 3 | 1 | 9 | 1 | 9 | 5 | 5 | 5 | 5 | 4 | 6 | 5 | 5 |
Number of Participants With Response to Clinical Global Impression-Improvement (CGI-I) Scale
"The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. very much improved; 2. much improved; 3. minimally improved; 4. no change; 5. minimally worse; 6. much worse; 7. very much worse. Higher scores indicated worse condition. Response was defined as >50% decrease from Baseline in CGI-I total score." (NCT03228394)
Timeframe: Day 1 (12 hours post start of infusion), Day 2, Day 3 post-infusion (60 hours post start of infusion), Day 4, Day 8, Day 11, Day 15, Day 22, Day 29, Day 34, Day 36, Day 57 and Day 71
| Intervention | Participants (Count of Participants) |
|---|
| Day 1 (12 hours post start of infusion): Very much or much improved | Day 1 (12 hours post start of infusion): Minimally or not improved | Day 2: Very much or much improved | Day 2: Minimally or not improved | Day 8: Very much or much improved | Day 8: Minimally or not improved | Day 15: Very much or much improved | Day 15: Minimally or not improved | Day 22: Very much or much improved | Day 22: Minimally or not improved | Day 29: Very much or much improved | Day 29: Minimally or not improved | Day 36: Very much or much improved | Day 36: Minimally or not improved | Day 57: Very much or much improved | Day 57: Minimally or not improved | Day 71: Very much or much improved | Day 71: Minimally or not improved |
|---|
| Ganaxolone Cohort 6 | 7 | 9 | 9 | 7 | 9 | 6 | 13 | 2 | 10 | 5 | 12 | 4 | 11 | 3 | 8 | 4 | 10 | 3 |
,| Placebo Cohort 6 | 3 | 14 | 3 | 14 | 6 | 9 | 6 | 10 | 8 | 7 | 6 | 10 | 5 | 7 | 6 | 6 | 7 | 5 |
Seizure Burden
Seizure Burden (%) Baseline and Percentage Change from Baseline by Time Point (NCT03350035)
Timeframe: Baseline (Pre-dose) to <-24hrs (Post Dose)
| Intervention | Percentage change from baseline (Mean) |
|---|
| Change from Baseline at 0 to <- 1 Hour Post-Dose | Change from Baseline at 0 to <- 4 Hour Post-Dose | Change from Baseline at >4 to <- 8 Hours Post-Dose | Change from Baseline at >8 to <- 16 Hours Post-Dose | Change from Baseline at >16 to <- 24 Hours Post-Dose | Change from Baseline at 0 to <- 24 Hours Post-Dose |
|---|
| High - GNX | -84.01 | -87.99 | -96.58 | -93.75 | -81.16 | -89.06 |
,| Low - GNX | -94.80 | -98.59 | -77.53 | -47.98 | -99.53 | -78.64 |
,| Medium - GNX | -74.63 | -71.75 | -59.80 | -53.29 | -48.25 | -56.10 |
Number of Participants With No SE Recurrence Per Principal Investigator
Number of participants with No SE Recurrence per Principal Investigator within 24hrs of starting treatment, during treatment period (excluding taper), during taper, during 24-hr follow-up period, and during follow-up period. (NCT03350035)
Timeframe: Baseline (within 24hrs of treatment) through follow up period, up to approximately 4 weeks.
| Intervention | Participants (Count of Participants) |
|---|
| Within 24hrs of starting treatment | During treatment period (excluding taper) | During taper | During 24-hr follow-up period | During follow-up period |
|---|
| High - GNX | 7 | 7 | 7 | 8 | 7 |
,| Low - GNX | 5 | 3 | 3 | 3 | 1 |
,| Medium - GNX | 4 | 4 | 2 | 3 | 3 |
Time to Cessation of SE
Summary of Time to SE Cessation (NCT03350035)
Timeframe: Time to SE Cessation, assessed up to 24 hours
| Intervention | Minutes (Median) |
|---|
| Low - GNX | 5.000 |
| Medium - GNX | 5.580 |
| High - GNX | 10.16 |
Number of Participants Who Required No Escalation of Treatment for Ongoing or Recurrent SE
Number of participants who Required No Escalation of Treatment for Ongoing or Recurrent SE (NCT03350035)
Timeframe: Drug initiation through follow-up period, up to approximately 4 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Low - GNX | 3 |
| Medium - GNX | 3 |
| High - GNX | 8 |
Number of Participants Who Did Not Require an IV Anesthetic Drug for SE Treatment
Number of participants who did not require an intravenous (IV) Anesthetic Drug (a third-line Treatment) for Status Epilepticus (SE) within the first 24 hours after Study Drug Initiation. (NCT03350035)
Timeframe: 24 hours post study drug initiation
| Intervention | Participants (Count of Participants) |
|---|
| Low - GNX | 5 |
| Medium - GNX | 4 |
| High - GNX | 8 |
Change From Baseline in Spielberger State-Trait Anxiety Inventory, 6-item Version
"The Spielberger State-Trait Anxiety Inventory was a 6-item questionnaire designed and validated. It is a reliable and sensitive measure of anxiety. The 6-item version has been shown to have acceptable reliability, producing similar scores as the full 20-item inventory for those with normal and raised levels of anxiety. Participants are prompted to respond to indicate how [the participant] feel right now, at this moment, followed by a list of common experiences like I feel calm, I am tense, I feel upset, I am relaxed I feel content and I am worried. Responses range from Not at all (1) to Very much (4), with overall scores ranging from 20-80, where higher scores reflected higher states of anxiety. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value." (NCT03460756)
Timeframe: Baseline (Day 1) through Day 119
| Intervention | Scores on a scale (Mean) |
|---|
| Day 2/4 | Day 7 | Day 8/10 | Day 15/17 | Day 36/38 |
|---|
| QHS (2-week) | -6.4 | -9.0 | -5.7 | -14.8 | -11.3 |
,| TID (2-week) | -11.7 | -11.7 | -20.0 | -33.3 | -31.7 |
Change From Baseline in Hamilton Depression Rating Scale 17-item Version Post Treatment
The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. (NCT03460756)
Timeframe: Baseline (Day 1) and Through Day 38 for 2 week treatment group and Day 71 and 119 for 4 week treatment groups
| Intervention | score on a scale (Mean) |
|---|
| Day 36/38 | Day 57/59 | Day 71 |
|---|
| 1125 mg (4-week) | -12.4 | -12.3 | -12.2 |
Change From Baseline in Hamilton Depression Rating Scale 17-item Version Post Treatment
The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. (NCT03460756)
Timeframe: Baseline (Day 1) and Through Day 38 for 2 week treatment group and Day 71 and 119 for 4 week treatment groups
| Intervention | score on a scale (Mean) |
|---|
| Day 36/38 |
|---|
| QHS (2-week) | -7.1 |
,| TID (2-week) | -19.0 |
Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Through Treatment
The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. (NCT03460756)
Timeframe: Baseline (Day 1) and through Day 10 for 2 week treatment group and Day 29 for 4 week treatment groups
| Intervention | score on a scale (Mean) |
|---|
| Day 2/4 | Day 8/10 | Day 15/17 | Day 22 | Day 29 |
|---|
| QHS (4-week) | -0.8 | -6.8 | -9.7 | -10.3 | -12.2 |
,| 1125 mg (4-week) | -2.6 | -10.2 | -9.4 | -12.0 | -14.0 |
Change From Baseline in Hamilton Depression Rating Scale 17-item Version (HAMD17) Through Treatment
The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. (NCT03460756)
Timeframe: Baseline (Day 1) and through Day 10 for 2 week treatment group and Day 29 for 4 week treatment groups
| Intervention | score on a scale (Mean) |
|---|
| Day 2/4 | Day 7 | Day 8/10 | Day 15/17 |
|---|
| QHS (2-week) | -5.7 | -6.7 | -10.5 | -8.8 |
,| TID (2-week) | -8.0 | -15.0 | -3.0 | -9.5 |
Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score
The EPDS is a validated 10-question depression assessment for postpartum women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression common in the postpartum period, such as changes in sleeping patterns. It consists of 10 multiple choice questions with scores for each question ranging from 0-3. Questions 1, 2, & 4 are scored 0, 1, 2 or 3 with top box scored as 0 and the bottom box scored as 3. Questions 3 and 5 to 10 are reverse scored, with the top box scored as a 3 and the bottom box scored as 0. Scores are then summed for a total score, which ranges from 0: no depression to 30: severe depression. Higher score indicates severe depression. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. (NCT03460756)
Timeframe: Baseline (Day 1) through Day 119
| Intervention | Score on a scale (Mean) |
|---|
| Day 2/4 | Day 8/10 | Day 15/17 | Day 22 | Day 29 | Day 36/38 | Day 57/59 | Day 89 | Day 119 |
|---|
| QHS (4-week) | -0.8 | -1.5 | -1.8 | -2.7 | -2.9 | -3.1 | -2.5 | -2.6 | -3.3 |
Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score
The EPDS is a validated 10-question depression assessment for postpartum women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression common in the postpartum period, such as changes in sleeping patterns. It consists of 10 multiple choice questions with scores for each question ranging from 0-3. Questions 1, 2, & 4 are scored 0, 1, 2 or 3 with top box scored as 0 and the bottom box scored as 3. Questions 3 and 5 to 10 are reverse scored, with the top box scored as a 3 and the bottom box scored as 0. Scores are then summed for a total score, which ranges from 0: no depression to 30: severe depression. Higher score indicates severe depression. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. (NCT03460756)
Timeframe: Baseline (Day 1) through Day 119
| Intervention | Score on a scale (Mean) |
|---|
| Day 2/4 | Day 7 | Day 8/10 | Day 15/17 | Day 36/38 |
|---|
| QHS (2-week) | -1.4 | -2.3 | -1.3 | -2.6 | -2.6 |
,| TID (2-week) | -0.5 | -2.0 | -3.0 | -5.0 | -2.0 |
Change From Baseline in Hamilton Depression Rating Scale 17-item Version Post Treatment
The HAMD17 was a 17-item clinician-rated instrument used to assess the range of symptoms that were most frequently observed in participants with major depression. All items were scored on an ordinal scale between 0 and 4 (8 items) or 0 and 2 (9 items) of increasing severity. Each of 17 items was rated by clinician with rating of 0: absent, 1: doubtful to mild, 2: mild to moderate, 3: moderate to severe, and 4: very severe. A total score (0 to 52) was calculated by adding scores of all 17 items, where 0 indicated no depression and 52 indicated severe depression. Higher score represented more severe condition. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. (NCT03460756)
Timeframe: Baseline (Day 1) and Through Day 38 for 2 week treatment group and Day 71 and 119 for 4 week treatment groups
| Intervention | score on a scale (Mean) |
|---|
| Day 36/38 | Day 57/59 | Day 89 | Day 119 |
|---|
| QHS (4-week) | -14.6 | -13.2 | -14.2 | -20.5 |
Number of Participants With Clinical Global Impression-Improvement
"The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. very much improved 2. much improved 3. minimally improved 4. no change 5. minimally worse 6. much worse 7. very much worse. Higher scores indicated worse condition. Only those participants with CGI- improvement have been presented." (NCT03460756)
Timeframe: Baseline through Day 119
| Intervention | Participants (Count of Participants) |
|---|
| Day 2/4 - Much Improved | Day 2/4 - Minimally Improved | Day 8/10 - Much Improved | Day 8/10 - Minimally Improved | Day 15/17 - Very much Improved | Day 15/17 - Much Improved | Day 15/17 - Minimally Improved | Day 22 - Very much Improved | Day 22 - Much Improved | Day 22 - Minimally Improved | Day 29 - Very much Improved | Day 29 - Much Improved | Day 29 - Minimally Improved | Day 36/38 - Very much Improved | Day 36/38 - Much Improved | Day 36/38 - Minimally Improved | Day 57/59 - Very Much Improved | Day 57/59 - Much Improved | Day 57/59 - Minimally Improved | Day 89 - Very much Improved | Day 89 - Much Improved | Day 89 - Minimally Improved | Day 119 - Very Much Improved | Day 119 - Much Improved | Day 119 - Minimally Improved |
|---|
| QHS (4-week) | 1 | 4 | 7 | 8 | 1 | 9 | 5 | 1 | 9 | 6 | 4 | 7 | 8 | 8 | 4 | 7 | 4 | 9 | 2 | 6 | 4 | 6 | 5 | 3 | 3 |
Change From Baseline in Edinburgh Postnatal Depression Scale (EPDS) Total Score
The EPDS is a validated 10-question depression assessment for postpartum women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression common in the postpartum period, such as changes in sleeping patterns. It consists of 10 multiple choice questions with scores for each question ranging from 0-3. Questions 1, 2, & 4 are scored 0, 1, 2 or 3 with top box scored as 0 and the bottom box scored as 3. Questions 3 and 5 to 10 are reverse scored, with the top box scored as a 3 and the bottom box scored as 0. Scores are then summed for a total score, which ranges from 0: no depression to 30: severe depression. Higher score indicates severe depression. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value. (NCT03460756)
Timeframe: Baseline (Day 1) through Day 119
| Intervention | Score on a scale (Mean) |
|---|
| Day 2/4 | Day 8/10 | Day 15/17 | Day 22 | Day 29 | Day 36/38 | Day 57/59 | Day 71 |
|---|
| 1125 mg (4-week) | -0.6 | -2.3 | -2.2 | -3.0 | -3.1 | -3.7 | -3.4 | -3.3 |
Number of Participants With Clinical Global Impression-Improvement
"The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. very much improved 2. much improved 3. minimally improved 4. no change 5. minimally worse 6. much worse 7. very much worse. Higher scores indicated worse condition. Only those participants with CGI- improvement have been presented." (NCT03460756)
Timeframe: Baseline through Day 119
| Intervention | Participants (Count of Participants) |
|---|
| Day 2/4 - Much Improved | Day 2/4 - Minimally Improved | Day 8/10 - Very much Improved | Day 8/10 - Much Improved | Day 8/10 - Minimally Improved | Day 15/17 - Very much Improved | Day 15/17 - Much Improved | Day 15/17 - Minimally Improved | Day 22 - Very much Improved | Day 22 - Much Improved | Day 22 - Minimally Improved | Day 29 - Very much Improved | Day 29 - Much Improved | Day 29 - Minimally Improved | Day 36/38 - Very much Improved | Day 36/38 - Much Improved | Day 36/38 - Minimally Improved | Day 57/59 - Very Much Improved | Day 57/59 - Much Improved | Day 57/59 - Minimally Improved | Day 71 - Very Much Improved | Day 71 - Much Improved | Day 71 - Minimally Improved |
|---|
| 1125 mg (4-week) | 4 | 15 | 3 | 14 | 11 | 6 | 15 | 9 | 7 | 16 | 6 | 11 | 16 | 5 | 12 | 10 | 10 | 9 | 14 | 7 | 8 | 14 | 6 |
Number of Participants With Clinical Global Impression-Improvement
"The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. very much improved 2. much improved 3. minimally improved 4. no change 5. minimally worse 6. much worse 7. very much worse. Higher scores indicated worse condition. Only those participants with CGI- improvement have been presented." (NCT03460756)
Timeframe: Baseline through Day 119
| Intervention | Participants (Count of Participants) |
|---|
| Day 2/4 - Much Improved | Day 2/4 - Minimally Improved | Day 7 - Very much Improved | Day 7 - Much Improved | Day 7 - Minimally Improved | Day 8/10 - Very much Improved | Day 8/10 - Much Improved | Day 8/10 - Minimally Improved | Day 15/17 - Very much Improved | Day 15/17 - Much Improved | Day 15/17 - Minimally Improved | Day 36/38 - Very much Improved | Day 36/38 - Much Improved | Day 36/38 - Minimally Improved |
|---|
| QHS (2-week) | 1 | 6 | 1 | 5 | 2 | 2 | 5 | 2 | 2 | 5 | 3 | 1 | 3 | 1 |
,| TID (2-week) | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 2 | 0 |
Change From Baseline in Spielberger State-Trait Anxiety Inventory, 6-item Version
"The Spielberger State-Trait Anxiety Inventory was a 6-item questionnaire designed and validated. It is a reliable and sensitive measure of anxiety. The 6-item version has been shown to have acceptable reliability, producing similar scores as the full 20-item inventory for those with normal and raised levels of anxiety. Participants are prompted to respond to indicate how [the participant] feel right now, at this moment, followed by a list of common experiences like I feel calm, I am tense, I feel upset, I am relaxed I feel content and I am worried. Responses range from Not at all (1) to Very much (4), with overall scores ranging from 20-80, where higher scores reflected higher states of anxiety. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value." (NCT03460756)
Timeframe: Baseline (Day 1) through Day 119
| Intervention | Scores on a scale (Mean) |
|---|
| Day 2/4 | Day 8/10 | Day 15/17 | Day 22 | Day 29 | Day 36/38 | Day 57/59 | Day 89 | Day 119 |
|---|
| QHS (4-week) | -1.8 | -11.8 | -14.5 | -13.0 | -17.13 | -20.5 | -16.3 | -14.7 | -16.7 |
Change From Baseline in Spielberger State-Trait Anxiety Inventory, 6-item Version
"The Spielberger State-Trait Anxiety Inventory was a 6-item questionnaire designed and validated. It is a reliable and sensitive measure of anxiety. The 6-item version has been shown to have acceptable reliability, producing similar scores as the full 20-item inventory for those with normal and raised levels of anxiety. Participants are prompted to respond to indicate how [the participant] feel right now, at this moment, followed by a list of common experiences like I feel calm, I am tense, I feel upset, I am relaxed I feel content and I am worried. Responses range from Not at all (1) to Very much (4), with overall scores ranging from 20-80, where higher scores reflected higher states of anxiety. Baseline was defined as the Day 1 assessment before study drug infusion. Change from Baseline is defined as post dose visit value minus Baseline value." (NCT03460756)
Timeframe: Baseline (Day 1) through Day 119
| Intervention | Scores on a scale (Mean) |
|---|
| Day 2/4 | Day 8/10 | Day 15/17 | Day 22 | Day 29 | Day 36/38 | Day 57/59 | Day 71 |
|---|
| 1125 mg (4-week) | -9.9 | -16.8 | -15.2 | -21.8 | -21.4 | -23.2 | -22.8 | -19.2 |
Number of Participants With Response to Hamilton Depression Rating Scale 17 Item (HAMD17)
HAMD17 Response was defined as ≥50% reduction from Baseline in total score. The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate greater symptom severity. Number of participants with response to HAMD-17 has been presented. (NCT03460756)
Timeframe: Day 2 (all treatment groups), Day 7 (TID & QHS), Day 8/10 (all treatment groups), Day 15/17 (all treatment groups), Day 22 and 29 (QHS, 1125mg), Day 36/38 (all treatment groups), Day 57/59 (QHS, 1125mg), Day 71 (1125mg), Day 89 (QHS), Day 119 (QHS)
| Intervention | Participants (Count of Participants) |
|---|
| Day 2/4 - Response | Day 8/10 - Response | Day 15/17 - Response | Day 22 - Response | Day 29 - Response | Day 36/38 - Response | Day 57/59 - Response | Day 71 - Response |
|---|
| 1125 mg (4-week) | 3 | 12 | 16 | 20 | 22 | 17 | 18 | 13 |
Number of Participants With Response to Hamilton Depression Rating Scale 17 Item (HAMD17)
HAMD17 Response was defined as ≥50% reduction from Baseline in total score. The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate greater symptom severity. Number of participants with response to HAMD-17 has been presented. (NCT03460756)
Timeframe: Day 2 (all treatment groups), Day 7 (TID & QHS), Day 8/10 (all treatment groups), Day 15/17 (all treatment groups), Day 22 and 29 (QHS, 1125mg), Day 36/38 (all treatment groups), Day 57/59 (QHS, 1125mg), Day 71 (1125mg), Day 89 (QHS), Day 119 (QHS)
| Intervention | Participants (Count of Participants) |
|---|
| Day 2/4 - Response | Day 7 - Response | Day 8/10 - Response | Day 15/17 - Response | Day 36/38 - Response |
|---|
| QHS (2-week) | 2 | 4 | 4 | 4 | 3 |
,| TID (2-week) | 0 | 1 | 0 | 1 | 2 |
Number of Participants With Hamilton Depression Rating Scale 17-item Remission
Remission was defined as an observed total score of 0 to 7. The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate greater symptom severity. Number of participants with HAMD-17 remission has been presented. (NCT03460756)
Timeframe: Day 8/10 (all treatment arms), Day 15/17 (all treatment arms), Day 22 and 29 (QHS & 1125mg), Day 36/38 (all treatment arms), Day 57/59 (QHS & 1125mg), Day 71 (1125mg), Day 89 & 119 (QHS)
| Intervention | Participants (Count of Participants) |
|---|
| Day 8/10 - Remission | Day 15/17 - Remission | Day 22 - Remission | Day 29 - Remission | Day 36/38 - Remission | Day 57/59 - Remission | Day 89 - Remission | Day 119 - Remission |
|---|
| QHS (4-week) | 1 | 4 | 3 | 7 | 9 | 5 | 7 | 8 |
Number of Participants With Response to Hamilton Depression Rating Scale 17 Item (HAMD17)
HAMD17 Response was defined as ≥50% reduction from Baseline in total score. The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate greater symptom severity. Number of participants with response to HAMD-17 has been presented. (NCT03460756)
Timeframe: Day 2 (all treatment groups), Day 7 (TID & QHS), Day 8/10 (all treatment groups), Day 15/17 (all treatment groups), Day 22 and 29 (QHS, 1125mg), Day 36/38 (all treatment groups), Day 57/59 (QHS, 1125mg), Day 71 (1125mg), Day 89 (QHS), Day 119 (QHS)
| Intervention | Participants (Count of Participants) |
|---|
| Day 2/4 - Response | Day 8/10 - Response | Day 15/17 - Response | Day 22 - Response | Day 29 - Response | Day 36/38 - Response | Day 57/59 - Response | Day 89 - Response | Day 119 - Response |
|---|
| QHS (4-week) | 0 | 7 | 7 | 8 | 10 | 12 | 8 | 9 | 10 |
Number of Participants With Hamilton Depression Rating Scale 17-item Remission
Remission was defined as an observed total score of 0 to 7. The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate greater symptom severity. Number of participants with HAMD-17 remission has been presented. (NCT03460756)
Timeframe: Day 8/10 (all treatment arms), Day 15/17 (all treatment arms), Day 22 and 29 (QHS & 1125mg), Day 36/38 (all treatment arms), Day 57/59 (QHS & 1125mg), Day 71 (1125mg), Day 89 & 119 (QHS)
| Intervention | Participants (Count of Participants) |
|---|
| Day 8/10 - Remission | Day 15/17 - Remission | Day 22 - Remission | Day 29 - Remission | Day 36/38 - Remission | Day 57/59 - Remission | Day 71 - Remission |
|---|
| 1125 mg (4-week) | 8 | 8 | 10 | 14 | 11 | 12 | 9 |
Number of Participants With Hamilton Depression Rating Scale 17-item Remission
Remission was defined as an observed total score of 0 to 7. The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed). Higher scores indicate greater symptom severity. Number of participants with HAMD-17 remission has been presented. (NCT03460756)
Timeframe: Day 8/10 (all treatment arms), Day 15/17 (all treatment arms), Day 22 and 29 (QHS & 1125mg), Day 36/38 (all treatment arms), Day 57/59 (QHS & 1125mg), Day 71 (1125mg), Day 89 & 119 (QHS)
| Intervention | Participants (Count of Participants) |
|---|
| Day 8/10 - Remission | Day 15/17 - Remission | Day 36/38 - Remission |
|---|
| QHS (2-week) | 1 | 2 | 1 |
,| TID (2-week) | 0 | 0 | 1 |
Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types
Arithmetic change in longest seizure free interval, based on primary seizure types during the double-blind treatment period of ganaxolone compared to placebo (NCT03572933)
Timeframe: End of the double-blind 17 week treatment period
| Intervention | days (Mean) |
|---|
| Placebo | -4.63 |
| Ganaxolone | -0.02 |
Caregiver Global Impression of Change in Attention
Caregiver global impression of change in attention during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives (NCT03572933)
Timeframe: End of the double-blind 17 week treatment period
| Intervention | Participants (Count of Participants) |
|---|
| Very Much Improved - Visit 5 (End of Week 17) | Much Improved - Visit 5 (End of Week 17) | Minimally Improved - Visit 5 (End of Week 17) | No Change - Visit 5 (End of Week 17) | Minimally Worse - Visit 5 (End of Week 17) | Much Worse - Visit 5 (End of Week 17) | Very Much Worse - Visit 5 (End of Week 17) |
|---|
| Ganaxolone | 1 | 2 | 21 | 18 | 1 | 1 | 1 |
,| Placebo | 1 | 7 | 14 | 23 | 1 | 1 | 0 |
Caregiver Global Impression of Change in Seizure Intensity and Duration
Caregiver global impression of change in seizure intensity and duration during the double-blind treatment period of ganaxolone compared to placebo. CGI-C is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. (NCT03572933)
Timeframe: End of the double-blind 17 week treatment period
| Intervention | Participants (Count of Participants) |
|---|
| Very Much Improved - Visit 5 (End of Week 17) | Much Improved - Visit 5 (End of Week 17) | Minimally Improved - Visit 5 (End of Week 17) | No Change - Visit 5 (End of Week 17) | 4Minimally Worse - Visit 5 (End of Week 17) | Much Worse - Visit 5 (End of Week 17) | Very Much Worse - Visit 5 (End of Week 17) |
|---|
| Ganaxolone | 2 | 15 | 11 | 10 | 3 | 2 | 2 |
,| Placebo | 1 | 5 | 11 | 21 | 5 | 4 | 0 |
Caregiver Global Impression of Change in Target Behavior
Caregiver global impression of change in target behavior during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives. (NCT03572933)
Timeframe: End of the double-blind 17 week treatment period
| Intervention | Participants (Count of Participants) |
|---|
| Very Much Improved - Visit 5 (End of Week 17) | Much Improved - Visit 5 (End of Week 17) | Minimally Improved - Visit 5 (End of Week 17) | No Change - Visit 5 (End of Week 17) | Minimally Worse - Visit 5 (End of Week 17) | Much Worse - Visit 5 (End of Week 17) | Very Much Worse - Visit 5 (End of Week 17) |
|---|
| Ganaxolone | 0 | 4 | 20 | 19 | 2 | 0 | 0 |
,| Placebo | 0 | 6 | 14 | 22 | 1 | 2 | 1 |
Clinical Global Impression of Improvement - Clinician
Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo (NCT03572933)
Timeframe: [Time Frame: End of the double-blind 17 week treatment period]
| Intervention | Participants (Count of Participants) |
|---|
| Very Much Improved - Visit 5 (End of Week 17) - Clinician | Much Improved - Visit 5 (End of Week 17) - Clinician | Minimally Improved - Visit 5 (End of Week 17) - Clinician | No Change - Visit 5 (End of Week 17) - Clinician | Minimally Worse - Visit 5 (End of Week 17) - Clinician | Much Worse - Visit 5 (End of Week 17) - Clinician | Very Much Worse - Visit 5 (End of Week 17) - Clinician |
|---|
| Ganaxolone | 0 | 7 | 19 | 16 | 2 | 3 | 1 |
,| Placebo | 0 | 7 | 13 | 19 | 9 | 0 | 0 |
Clinical Global Impression of Improvement - Parent/Caregiver
Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses. (NCT03572933)
Timeframe: End of the double-blind 17 week treatment period
| Intervention | Participants (Count of Participants) |
|---|
| Very Much Improved - Visit 5 (End of Week 17) - Parent/Caregiver | Much Improved - Visit 5 (End of Week 17) - Parent/Caregiver | Minimally Improved - Visit 5 (End of Week 17) - Parent/Caregiver | No Change - Visit 5 (End of Week 17) - Parent/Caregiver | Minimally Worse - Visit 5 (End of Week 17) - Parent/Caregiver | Much Worse - Visit 5 (End of Week 17) - Parent/Caregiver | Very Much Worse - Visit 5 (End of Week 17) - Parent/Caregiver |
|---|
| Ganaxolone | 0 | 13 | 17 | 14 | 2 | 2 | 0 |
,| Placebo | 1 | 7 | 13 | 22 | 4 | 1 | 0 |
Percentage of Seizure-free Days for Major Motor Seizure Types
Percentage of Seizure-free Days for Major Motor Seizure types during the double-blind treatment period of ganaxolone compared to placebo. The major motor seizure types include bilateral tonic (sustained motor activity = 3 seconds), generalized tonic-clonic, atonic/drop, bilateral clonic, and focal to bilateral tonic-clonic. (NCT03572933)
Timeframe: End of the double-blind 17 week treatment period
| Intervention | percent of seizure-free days (Mean) |
|---|
| Baseline | 17-week-Post-Baseline Phase | Arithmetic Change from Baseline |
|---|
| Ganaxolone | 22.57 | 32.29 | 9.62 |
,| Placebo | 30.32 | 36.17 | 5.86 |
Summary of 28-day Seizure Frequency for Major Motor Seizure Types
"Summary of 28-day seizure frequency for Major Motor Seizure Types during the double-blind treatment period relative to the 6-week prospective baseline period~Note: Summaries are based on the sum of the individual seizures, the countable seizures, and the clusters with uncountable seizures (each cluster with uncountable seizures counts as 1 seizure). Within the baseline and post baseline intervals, 28-day seizure frequency was calculated as the total number of seizures in the interval divided by the number of days with available seizure data in the interval, multiplied by 28." (NCT03572933)
Timeframe: End of the double-blind 17 week treatment period
| Intervention | Seizures per day (Median) |
|---|
| Baseline (Median) | 17 week-post baseline phase (Median) |
|---|
| Ganaxolone | 54.00 | 45.03 |
,| Placebo | 49.17 | 55.50 |
50% Primary Seizure Reduction
Percent of subjects experiencing a greater than or equal to 50% reduction in 28-day primary seizure frequency relative to the 12-week baseline (NCT03865732)
Timeframe: End of the double-blind 17 week treatment period
| Intervention | Participants (Count of Participants) |
|---|
| Placebo | 4 |
| Ganaxolone | 5 |
Summary of 28-day Seizure Frequency Through 17 Week Post-Baseline Phase (Median Percent Change)
Summary of 28-Day Seizure Frequency for Seizure Types through 17 week Post-Baseline Phase (Median Percent Change) (NCT03865732)
Timeframe: End of the double-blind 17 week treatment period
| Intervention | Median % Change in Number of Seizures (Median) |
|---|
| Placebo | -23.97 |
| Ganaxolone | -61.52 |
Percent Change From Baseline in 28-day Seizure Frequency Through the End of 12-Week Treatment Period
Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor without impairment of consciousness or awareness, focal (motor or non-motor) with impairment of consciousness or awareness, focal to bilateral tonic-clonic, generalized tonic-clonic. Baseline 28-day seizure frequency was calculated as the total number of primary seizures in the Baseline period divided by the number of days with non-missing seizure data in the Baseline period, multiplied by 28. The Baseline Visit was defined as Week 0. Percent change from Baseline in 28-day seizure frequent was calculated as the difference in post-Baseline 28-day seizure frequency and Baseline 28-day seizure frequency, divided by Baseline 28-day seizure frequency, multiplied by 100. (NCT04285346)
Timeframe: Baseline and Up to Week 12
| Intervention | Percent change (Median) |
|---|
| Treatment Period: Ganaxolone | -16.61 |
Percentage of Participants Experiencing a >=50 Percent Reduction in 28-day Primary Seizure Frequency Through the End of the 12-week Treatment Period Compared to the Baseline Period
Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor without impairment of consciousness or awareness, focal (motor or non-motor) with impairment of consciousness or awareness, focal to bilateral tonic-clonic, generalized tonic-clonic. Percentage of participants reporting >=50 percent reduction in seizure frequency has been presented. (NCT04285346)
Timeframe: Baseline and up to 12 Weeks
| Intervention | Percentage of participants (Number) |
|---|
| Treatment Period: Ganaxolone | 30.4 |