Phase 3 Study of Adjunctive Ganaxolone in Adults With Dru... | NCT01963208 | Trialant
NCT01963208
Sponsor
Marinus Pharmaceuticals
Status
Completed
Last Update Posted
Feb 14, 2023Actual
Enrollment
405Actual
Phase
Phase 3
Conditions
Drug Resistant Partial Onset Seizure
Interventions
ganaxolone
Placebo
Countries
United States
Australia
Bulgaria
Germany
Poland
Russia
Protocol Section
Identification Module
NCT ID
NCT01963208
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1042-0603
Secondary IDs
Not provided
Brief Title
Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures and Open-label Extension
Official Title
A Multicenter, Double Blind, Randomized, Placebo-Controlled Trial to Determine the Efficacy and Safety of Ganaxolone as Adjunctive Therapy for Adults With Drug-Resistant Partial-Onset Seizures Followed by Long-term Open-Label Treatment
Acronym
Not provided
Organization
Marinus PharmaceuticalsINDUSTRY
Status Module
Record Verification Date
Jan 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Oct 2013
Primary Completion Date
May 2016Actual
Completion Date
Oct 2016Actual
First Submitted Date
Oct 11, 2013
First Submission Date that Met QC Criteria
Oct 11, 2013
First Posted Date
Oct 16, 2013Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 21, 2022
Results First Submitted that Met QC Criteria
Jan 18, 2023
Results First Posted Date
Feb 14, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Oct 27, 2017
Certification/Extension First Submitted that Passed QC Review
Oct 27, 2017
Certification/Extension First Posted Date
Nov 1, 2017Actual
Last Update Submitted Date
Jan 18, 2023
Last Update Posted Date
Feb 14, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Marinus PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The study will evaluate the effectiveness and safety of an investigational drug-ganaxolone - on partial seizure frequency in adults with epilepsy taking a maximum of 3 antiepileptic medications (AEDs).
Detailed Description
This is a 2-cohort study comprised of 2 phases in each cohort. Phase 1 is a double-blind (DB) phase followed by Phase 2, an open-label phase. Cohort 1 will provide tolerability, safety, and PK information for ganaxolone 1200 milligram per day (mg/day), 1800 mg/day and placebo. Cohort 2 will investigate the efficacy, tolerability and safety of ganaxolone 1800 mg/day compared to placebo. Cohort 1 (N= approximately 50) will enroll into a 67-week study comprised of a 4-week prospective baseline period plus 4 week retrospective baseline followed by two treatment phases: a 9-week randomized DB placebo-controlled treatment phase followed by a 52-week open label treatment phase. Cohort 2 (N=150) will enroll into a 72-week study comprised of a 8-week prospective baseline period followed by two treatment phases: a 14-week randomized DB placebo-controlled treatment phase followed by a 52-week open label treatment phase.
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).
Baseline and Week 14
Secondary Outcomes
Measure
Description
Time Frame
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.
Up to Week 14
Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Titration + Maintenance Period
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Able to give informed consent in writing, or have a legally authorized representative able to do so
Willing to enter and participate for the full term of the double blind phase and willing to enter into the open-label phase
Male or female outpatients > 18 years of age
Have a confident diagnosis of drug-resistant epilepsy with partial-onset seizures (POS), with or without secondary generalization, for ≥2 years. Have residual POS despite having been treated in the past with at least 2 approved anti-epilepsy drugs (AEDs) either alone or in combination
Based on history, participants would be anticipated to have at least 3 POS during each 4-week Baseline period and unlikely to have 21 or more consecutive POS-free days
Currently being treated and maintained with a stable regimen of 1, 2, or 3 AEDs
Able and willing to maintain daily seizure calendar
Able and willing to take drug with food twice daily
Sexually active women of childbearing potential must use acceptable birth control and have a negative pregnancy test at all visits
Exclusion Criteria:
Have had previous exposure to ganaxolone
Known sensitivity or allergy to any component in the study drug, progesterone, or other related steroid compounds
Exposure to any investigational drug or device <30 days prior to screening, or plans to take another investigational drug at any time during the study
Time of onset of epilepsy treatment <2 years prior to enrollment
Have generalized epilepsy, such as Lennox-Gastaut syndrome, juvenile myoclonic epilepsy, absence epilepsy, or non-epileptic seizures within the last 12- month period prior to study entry
Have less than 3 POS seizures in a 28-day period or more than 21 consecutive seizure-free days during the Baseline period
Have only simple partial seizures without any observable motor component
Have innumerable seizures or status epilepticus within the last 12-months prior to screening
Have more than 100 POS per 4-week Baseline period
Have seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or central nervous system (CNS) disease deemed progressive, metabolic illness, or progressive degenerative disease
Current use of vigabatrin is not permitted. If prior use of vigabatrin, must have documented stable visual fields
Current use of ezogabine is not permitted. If prior use, must have been off the medication for at least 3 months prior to screening and have had documented normal fundoscopic exam by ophthalmologist
Are planning surgery, or to be evaluated for surgery, during the double-blind phase to control seizures including VNS implantation
Are suffering from acute or progressive neurological disease, moderate or severe psychiatric disease, or severe mental abnormalities that are likely to require changes in drug therapy during the double-blind portion of the study or interfere with the objectives of the study or the ability to adhere to the protocol requirements
Have a history of an actual suicide attempt in the last 5 years or more than 1 lifetime suicide attempt
Have a positive urine drug screen at Screening or meet criteria for current or historical Substance Use Disorder (DSM-V criteria) within the past 5 years.
Have any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect participant safety or study outcome, including but not limited to: clinically significant cardiac, renal, pulmonary, gastrointestinal, hematologic or hepatic conditions; or a condition that affects the absorption, distribution, metabolism or excretion of drugs
Have elevated ALT (SGPT) or AST (SGOT) greater than 3 times upper limits of normal, or total bilirubin greater than 1.5 times ULN
Have a history of malignancy within the past 2 years, with the exception of basal cell carcinoma
Are currently following or planning to follow a ketogenic diet
Use of dietary supplements or herbal preparations are not permitted if participant has been using them consistently for less than 6 months prior to screening, or does not plan on remaining on stable doses for the duration of the double blind phase. Use of St. John's Wort is not permitted
Females who are pregnant, currently breastfeeding or planning to become pregnant during the duration of the study
A history of chronic noncompliance with drug regimens
Inability to withhold grapefruit and grapefruit juice from diet during the entire clinical trial
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
Not provided
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Not provided
Locations
Facility
Status
City
State
ZIP
Country
Contacts
University of Alabama Epilepsy Center
Birmingham
Alabama
35294-3280
United States
University of Alabama at Birmingham
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
A total of 405 participants were enrolled in the study. Double Blind: Cohort 1 comprised of Titration period (Week 0 to Week 1) and Maintenance period (Week 1 to Week 9). Double Blind: Cohort 2 comprised of Titration period (Week 0 to Week 2) and Maintenance period (Week 2 to Week 14).
Recruitment Details
This was a 2-cohort study where each cohort comprised of 2 treatment phases. Phase 1 was a double-blind phase followed by Phase 2, an open-label phase. The study analyzed safety, tolerability and pharmacokinetics (PK) of Ganaxolone when compared with placebo in both the cohorts.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Double Blind: Cohort 1 - Ganaxolone
Participants were administered ganaxolone 1200 milligrams per day (mg/day) and 1800 mg/day + Antiepileptic drug (AED). Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
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.
Baseline and Week 14
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.
At Week 14
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.
Baseline and Week 2 to Week 14
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.
Baseline and Week 14
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.
Baseline and Week 2 to Week 14
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.
Baseline and Week 2 to Week 14
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.
Up to Week 14
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.
Week 2 to Week 14
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
Week 2 to Week 14
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
Up to Week 14
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%.
Up to Week 14
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.
Baseline and Week 14
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.
Week 8 and Week 14
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.
At Week 8
Birmingham
Alabama
35294
United States
Xenoscience Inc.
Phoenix
Arizona
85004
United States
The MORE Foundation
Sun City
Arizona
85351
United States
Clinical Trials Inc.
Little Rock
Arkansas
72205
United States
Neuro-Pain Medical Center, Inc
Fresno
California
93710
United States
Neurological Research Institute
Santa Monica
California
90404
United States
University of Colorado- Anschutz Outpatient Pavilion
Aurora
Colorado
80045
United States
Neuroscience Consulants
Miami
Florida
33176
United States
Medsol Clinical Research Center
Port Charlotte
Florida
33952
United States
Consultants in Epilepsy & Neurology
Boise
Idaho
83702
United States
Bluegrass Epilepsy Research, LLC
Lexington
Kentucky
40504
United States
Mid-Atlantic Epilepsy Center
Bethesda
Maryland
20817
United States
Bringham and Women's Hospital
Boston
Massachusetts
02115
United States
Minneapolis Clinic of Neurology
Golden Valley
Minnesota
55422
United States
The Comprehensive Epilepsy Care Center for Children and Adults
Chesterfield
Missouri
63017
United States
Cooper Medical Center of Rowan University
Camden
New Jersey
08103
United States
Northeast Regional Epilepsy Group
Hackensack
New Jersey
07601
United States
Five Towns Neuroscience Research
Cedarhurst
New York
11516
United States
Northeast Regional Epilepsy Group
Middletown
New York
10941
United States
Winthrop University Hospital
Mineola
New York
11501
United States
New York University Comprehensive Epilepsy Center
New York
New York
10016
United States
Northeast Regional Epilepsy Group
New York
New York
10017
United States
Wake Forest Health Sciences
Winston-Salem
North Carolina
27157
United States
Ohio Clinical Research Partners, LLC
Canton
Ohio
44718
United States
Ohio State University
Columbus
Ohio
43221
United States
Lynn Health Institute
Oklahoma City
Oklahoma
73112
United States
Sooner Clinical Research
Oklahoma City
Oklahoma
73112
United States
Jefferson Comprehensive Epilepsy Center
Philadelphia
Pennsylvania
19107
United States
Temple University School of Medicine
Philadelphia
Pennsylvania
19140
United States
Neurology Consultants of Dallas
Dallas
Texas
75231
United States
Texas Epilepsy Group
Dallas
Texas
75251
United States
Rainier Clinical Research Center, Inc.
Renton
Washington
98057
United States
Royal Prince Alfred Hospital
Camperdown
New South Wales
2050
Australia
The Prince of Wales Hospital
Randwick
New South Wales
2031
Australia
Westmead Hospital
Westmead
New South Wales
2145
Australia
Flinders Medical Center
Bedford Park
South Australia
5042
Australia
St. Vincent's Hospital
Fitzroy
Victoria
3065
Australia
The Florey Institute of Neuroscience and Mental Health
Heidelberg
Victoria
3084
Australia
The Royal Melbourne Hospital
Parkville
Victoria
3050
Australia
MHAT
Blagoevgrad
2700
Bulgaria
UMHAT Dr. Georgi Stranski Clinic of Neurology
Pleven
5800
Bulgaria
Medical Centre-Teodora
Rousse
7000
Bulgaria
Medical Center Excelsior 4
Sofia
1000
Bulgaria
SHATNP
Sofia
1113
Bulgaria
MHAT Lyulin Department of Neurology
Sofia
1336
Bulgaria
UMHAT Alexandrovska Clinic of Nerve Diseases
Sofia
1431
Bulgaria
Medical Center Ekvita Ltd
Varna
9000
Bulgaria
Epilepsieklinik
Bernau
16321
Germany
Krankenhaus Mara Epilepsie-Zentrum
Bielefeld
33617
Germany
Klinik fur Epileptologie
Bonn
53105
Germany
Neuro-Consil
Dussseldorf
40212
Germany
Universitatsklinikum GieBen und Marburg
Marburg
35043
Germany
Universitatsklin Kum Ulm
Ulm
89081
Germany
Novo-Med
Jaworowa
Poland
Centrum Medycne Dendryt
Katowice
Poland
Indywidualna Praktyka ul Narutowicza
Lublin
Poland
Wojewodzki Szpital Specjalistyczny Oddzial
Lublin
Poland
Fundacja Epileptologii Wiertnicza
Warsaw
Poland
Instytut Psychiatrii i Neurologii
Warsaw
Poland
Kazan State Medical University
Kazan'
420064
Russia
Moscow
107150
Russia
Moscow
117049
Russia
Nizhny Novgorod
603163
Russia
Novosibirsk
630054
Russia
City Neurological Center
Novosibirsk
630091
Russia
Saint Petersburg
192019
Russia
Saint Petersburg
194291
Russia
Saint Petersburg
Russia
Samara
443095
Russia
Yaroslavl
150030
Russia
FG001
Double Blind: Cohort 1 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
FG002
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
FG003
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
FG004
Open Label: Ganaxolone in Double-blind Phase
Following the completion of the double-blind phase, participants randomized to ganaxolone remained on the drug at 1800 mg/day + AED. Participants from Double Blind: Cohort 1 - Ganaxolone and Double Blind: Cohort 2 - Ganaxolone were combined to enter in Open Label: Ganaxolone in Double-blind Phase
FG005
Open Label: Placebo in Double-blind Phase
Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone + AED. Participants from Double Blind: Cohort 1 - Placebo and Double Blind: Cohort 2 - Placebo were combined to enter in Open Label: Placebo in Double-blind Phase
FG00024 subjects
FG00122 subjects
FG002179 subjects
FG003180 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG00023 subjects
FG00119 subjects
FG002135 subjects
FG003154 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG0001 subjects
FG0013 subjects
FG00244 subjects
FG00326 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0010 subjects
FG00230 subjects
FG00311 subjects
FG0040 subjects
FG0050 subjects
Withdrawal by Subject
FG0000 subjects
FG0012 subjects
FG0028 subjects
FG0039 subjects
FG004
Non-compliance
FG0000 subjects
FG0010 subjects
FG0024 subjects
FG0030 subjects
FG004
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0033 subjects
FG004
Other
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0031 subjects
FG004
Insufficient Clinical Response
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Treatment Phase 2 (Up to Week 68)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004158 subjects
FG005173 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Modified intent to treat (mITT) population: all randomized participants who received at least 1 dose of study medication and provided any post Baseline seizure outcome data.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Double Blind: Cohort 1 - Ganaxolone
Participants were administered ganaxolone 1200 mg/day and 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
BG001
Double Blind: Cohort 1 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
BG002
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
BG003
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00024
BG00121
BG002178
BG003172
BG004395
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00035.1± 10.25
BG00141.1± 11.83
BG00240.6± 12.48
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00013
BG00112
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0002
BG0012
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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).
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Median
95% Confidence Interval
Percent change
Baseline and Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Units
Counts
Participants
OG000178
OG001172
Title
Denominators
Categories
Title
Measurements
OG000-21.28(-29.60 to -14.29)
OG001-10.25(-20.14 to -1.28)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Rank ANCOVA
0.1788
The null hypothesis is that there is no difference between the distributions of the two treatment groups with respect to percent change in seizure frequency.
Median Difference (Final Values)
-7.06
2-Sided
95
-17.44
3.52
Other
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Count of Participants
Participants
Up to Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Units
Counts
Participants
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Mean
Standard Deviation
Seizure free days
Baseline and Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Count of Participants
Participants
At Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Median
95% Confidence Interval
Percent change
Baseline and Week 2 to Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Mean
Standard Deviation
Seizures per 28 days
Baseline and Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Mean
Standard Deviation
Seizures per 28 days
Baseline and Week 2 to Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Mean
Standard Deviation
Seizure free days
Baseline and Week 2 to Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Number
Percentage of participants
Up to Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Number
Percentage of participants
Week 2 to Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Secondary
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
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Number
Percentage of participants
Week 2 to Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Units
Counts
Participants
Secondary
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
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Number
Percentage of participants
Up to Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Units
Counts
Participants
Secondary
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%.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Mean
Standard Deviation
Percentage of time spent
Up to Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Units
Counts
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Mean
Standard Deviation
Percent change
Baseline and Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Count of Participants
Participants
Week 8 and Week 14
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Secondary
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.
mITT Population. Only those participants with data available at the specified data points were analyzed.
Posted
Count of Participants
Participants
At Week 8
ID
Title
Description
OG000
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
OG001
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Time Frame
Week -8 through Week 14 in Double blind phase and from Week 16 to Week 68 in open label phase
Description
Safety Population: included all randomized participants who received at least 1 dose of study medication.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Double Blind: Cohort 1 - Ganaxolone
Participants were administered ganaxolone 1200 mg/day and 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
0
24
0
24
10
24
EG001
Double Blind: Cohort 1 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
0
21
0
21
3
21
EG002
Double Blind: Cohort 2 - Ganaxolone
Participants were administered Ganaxolone 1800 mg/day + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
0
179
9
179
91
179
EG003
Double Blind: Cohort 2 - Placebo
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
0
176
9
176
42
176
EG004
Open Label: Ganaxolone in Double-blind Phase
Following the completion of the double-blind phase, participants randomized to ganaxolone remained on the drug at 1800 mg/day + AED. Participants from Double Blind: Cohort 1 - Ganaxolone and Double Blind: Cohort 2 - Ganaxolone were combined to enter in Open Label: Ganaxolone in Double-blind Phase
0
158
12
158
42
158
EG005
Open Label: Placebo in Double-blind Phase
Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone + AED. Participants from Double Blind: Cohort 1 - Placebo and Double Blind: Cohort 2 - Placebo were combined to enter in Open Label: Placebo in Double-blind Phase
1
173
12
173
67
173
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Coronary artery disease
Cardiac disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG0031 events1 affected176 at risk
EG0040 events0 affected158 at risk
EG0050 events0 affected173 at risk
Small intestinal obstruction
Gastrointestinal disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0021 events1 affected179 at risk
EG003
Oesophageal obstruction
Gastrointestinal disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0021 events1 affected179 at risk
EG003
Gait disturbance
General disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0021 events1 affected179 at risk
EG003
Asthenia
Gastrointestinal disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Lung abscess
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Pulmonary tuberculosis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0021 events1 affected179 at risk
EG003
Meningitis viral
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Appendicitis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Tongue injury
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0021 events1 affected179 at risk
EG003
Foot fracture
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Subdural haematoma
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0021 events1 affected179 at risk
EG003
Spinal column injury
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Accidental overdose
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Ankle fracture
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Clavicle fracture
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Ligament rupture
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0021 events1 affected179 at risk
EG003
Rhabdomyolysis
Musculoskeletal and connective tissue disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected24 at risk
EG0010 events0 affected21 at risk
EG0020 events0 affected179 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Units
Counts
Participants
OG000178
OG001172
Title
Denominators
Categories
Title
Measurements
OG0001.47± 4.396
OG0011.01± 4.223
Units
Counts
Participants
OG000140
OG001159
Title
Denominators
Categories
Very much improved
Title
Measurements
OG0007
OG0015
Much improved
Title
Measurements
OG00028
OG00130
Minimally improved
Title
Measurements
OG00041
OG00147
No change
Title
Measurements
OG00056
OG00167
Minimally worse
Title
Measurements
OG0006
OG0018
Much worse
Title
Measurements
OG0002
OG0012
Very much worse
Title
Measurements
OG0000
OG0010
Units
Counts
Participants
OG000166
OG001169
Title
Denominators
Categories
Title
Measurements
OG000-20.56(-31.56 to -12.69)
OG001-12.50(-20.78 to -3.03)
Units
Counts
Participants
OG000178
OG001172
Title
Denominators
Categories
Title
Measurements
OG000-1.46± 9.650
OG001-0.33± 11.040
Units
Counts
Participants
OG000166
OG001169
Title
Denominators
Categories
Title
Measurements
OG000-1.67± 11.809
OG001-0.64± 12.153
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.
Units
Counts
Participants
OG000166
OG001169
Title
Denominators
Categories
Title
Measurements
OG0001.63± 4.824
OG0011.20± 4.462
Units
Counts
Participants
OG000178
OG001172
Title
Denominators
Categories
Reduction ≥ 80%
Title
Measurements
OG0007.3
OG0012.33
Reduction ≥ 60%
Title
Measurements
OG00020.79
OG00116.86
Reduction ≥ 40%
Title
Measurements
OG00033.15
OG00129.65
Reduction ≥ 20%
Title
Measurements
OG00051.69
OG00143.6
Units
Counts
Participants
OG000178
OG001172
Title
Denominators
Categories
Reduction ≥ 80%
Title
Measurements
OG0008.43
OG0015.81
Reduction ≥ 60%
Title
Measurements
OG00024.16
OG00118.02
Reduction ≥ 40%
Title
Measurements
OG00033.71
OG00131.4
Reduction ≥ 20%
Title
Measurements
OG00047.19
OG00142.44
OG000178
OG001172
Title
Denominators
Categories
Title
Measurements
OG0001.12
OG0010
OG000178
OG001172
Title
Denominators
Categories
Title
Measurements
OG00017.98
OG00118.02
Participants
OG000178
OG001172
Title
Denominators
Categories
Title
Measurements
OG00024.00± 22.457
OG00117.58± 12.743
Participants were administered Placebo + AED. Following the completion of the double-blind phase, participants randomized to placebo were transitioned to ganaxolone while participants randomized to ganaxolone remained on the drug at 1800 mg/day in the open-label phase.