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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01963208
Registration number
NCT01963208
Ethics application status
Date submitted
11/10/2013
Date registered
16/10/2013
Date last updated
14/02/2023
Titles & IDs
Public title
Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures and Open-label Extension
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Scientific 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
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Secondary ID [1]
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1042-0603
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Drug Resistant Partial Onset Seizure
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Condition category
Condition code
Neurological
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Epilepsy
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Neurological
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Other neurological disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - ganaxolone
Treatment: Drugs - Placebo
Experimental: Double Blind - Cohort 1 - Ganaxolone - 1200 mg/day and 1800 mg/day + AED
Placebo Comparator: Double Blind - Cohort 1 - Placebo - Placebo + AED
Experimental: Open Label - Ganaxolone in Double-blind phase - 1800 mg/day + AED
Experimental: Double Blind - Cohort 2 - Ganaxolone - 1800 mg/day + AED
Placebo Comparator: Double Blind - Cohort 2 - Placebo - Placebo +AED
Experimental: Open Label - Placebo in Double-blind phase - 1800 mg/day + AED
Treatment: Drugs: ganaxolone
200 mg and 225 mg capsules; target dose 1800 mg/day dosed 900mg 2x/day
Treatment: Drugs: Placebo
placebo
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
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Assessment method [1]
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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).
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Timepoint [1]
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Baseline and Week 14
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Secondary outcome [1]
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Double Blind: Cohort 2: Number of Participants With =50% Responder Rate During Titration + Maintenance Period
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Assessment method [1]
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A 50% responder was a participant who experienced at least a 50% decrease in 28-day seizure frequency compared to Baseline.
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Timepoint [1]
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Up to Week 14
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Secondary outcome [2]
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Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Titration + Maintenance Period
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline and Week 14
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Secondary outcome [3]
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Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 14
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Assessment method [3]
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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.
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Timepoint [3]
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At Week 14
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Secondary outcome [4]
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Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Maintenance Period
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Assessment method [4]
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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.
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Timepoint [4]
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Baseline and Week 2 to Week 14
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Secondary outcome [5]
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Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
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Assessment method [5]
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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.
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Timepoint [5]
0
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Baseline and Week 14
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Secondary outcome [6]
0
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Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Maintenance Period
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Assessment method [6]
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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.
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Timepoint [6]
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Baseline and Week 2 to Week 14
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Secondary outcome [7]
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Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Maintenance Period
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Assessment method [7]
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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.
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Timepoint [7]
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Baseline and Week 2 to Week 14
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Secondary outcome [8]
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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
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Assessment method [8]
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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.
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Timepoint [8]
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Up to Week 14
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Secondary outcome [9]
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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
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Assessment method [9]
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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.
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Timepoint [9]
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Week 2 to Week 14
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Secondary outcome [10]
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Double Blind: Cohort 2: Percentage of Seizure Free Participants During the Maintenance Period
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Assessment method [10]
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Percentage of participants who completed the study without any seizures is presented
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Timepoint [10]
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Week 2 to Week 14
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Secondary outcome [11]
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Double Blind: Cohort 2: Percentage of Participants Who Experienced at Least One 28-day Seizure Free Period During Titration + Maintenance Phase
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Assessment method [11]
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Percentage of participants who experienced at least one 28-day seizure free period is presented
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Timepoint [11]
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Up to Week 14
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Secondary outcome [12]
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Double Blind: Cohort 2: Longest Percent of Time Spent Seizure-free During Titration + Maintenance Period
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Assessment method [12]
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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%.
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Timepoint [12]
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Up to Week 14
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Secondary outcome [13]
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Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency for Different Subtypes of Seizures During Titration + Maintenance Period
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Assessment method [13]
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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.
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Timepoint [13]
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Baseline and Week 14
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Secondary outcome [14]
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Double Blind: Cohort 2: Number of Participants With Patient Global Impression of Change - Improvement (PGI-I) at Week 8 and Week 14
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Assessment method [14]
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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.
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Timepoint [14]
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Week 8 and Week 14
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Secondary outcome [15]
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Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 8
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Assessment method [15]
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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.
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Timepoint [15]
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At Week 8
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Eligibility
Key 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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/10/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/10/2016
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Sample size
Target
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Accrual to date
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Final
405
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Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
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Recruitment hospital [1]
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Royal Prince Alfred Hospital - Camperdown
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Recruitment hospital [2]
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The Prince of Wales Hospital - Randwick
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Recruitment hospital [3]
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Westmead Hospital - Westmead
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Recruitment hospital [4]
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Flinders Medical Center - Bedford Park
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Recruitment hospital [5]
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St. Vincent's Hospital - Fitzroy
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Recruitment hospital [6]
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The Florey Institute of Neuroscience and Mental Health - Heidelberg
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Recruitment hospital [7]
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The Royal Melbourne Hospital - Parkville
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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2031 - Randwick
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Recruitment postcode(s) [3]
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2145 - Westmead
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Recruitment postcode(s) [4]
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5042 - Bedford Park
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Recruitment postcode(s) [5]
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3065 - Fitzroy
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Recruitment postcode(s) [6]
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3084 - Heidelberg
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Recruitment postcode(s) [7]
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3050 - Parkville
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Recruitment outside Australia
Country [1]
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0
United States of America
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State/province [1]
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Alabama
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0
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United States of America
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State/province [2]
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Arizona
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United States of America
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State/province [3]
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Arkansas
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United States of America
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State/province [4]
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California
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0
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United States of America
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Colorado
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United States of America
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State/province [6]
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Florida
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United States of America
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State/province [7]
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Idaho
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United States of America
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State/province [8]
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Kentucky
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0
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United States of America
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State/province [9]
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Maryland
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Country [10]
0
0
United States of America
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Massachusetts
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0
0
United States of America
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State/province [11]
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Minnesota
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0
0
United States of America
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Missouri
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0
0
United States of America
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New Jersey
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United States of America
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State/province [14]
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New York
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United States of America
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State/province [15]
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North Carolina
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Ohio
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United States of America
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Oklahoma
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United States of America
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Pennsylvania
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Texas
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United States of America
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State/province [20]
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Washington
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Country [21]
0
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Bulgaria
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State/province [21]
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Blagoevgrad
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0
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Bulgaria
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State/province [22]
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Pleven
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Country [23]
0
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Bulgaria
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State/province [23]
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Ruse
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Bulgaria
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State/province [24]
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Sofia
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0
0
Bulgaria
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State/province [25]
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Varna
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0
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Germany
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Bernau
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Germany
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Bielefeld
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Germany
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Bonn
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0
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Germany
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State/province [29]
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Dussseldorf
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Germany
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Marburg
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Germany
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State/province [31]
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Ulm
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Poland
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State/province [32]
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Jaworowa
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Poland
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State/province [33]
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Katowice
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Poland
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State/province [34]
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Lublin
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Poland
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State/province [35]
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Warszawa
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Russian Federation
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State/province [36]
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Kazan
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Country [37]
0
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Russian Federation
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State/province [37]
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Moscow
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Country [38]
0
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Russian Federation
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State/province [38]
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Nizhniy Novgorod
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Country [39]
0
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Russian Federation
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State/province [39]
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Novosibirsk
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Country [40]
0
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Russian Federation
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State/province [40]
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Saint Petersburg
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Country [41]
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Russian Federation
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State/province [41]
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Samara
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Country [42]
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Russian Federation
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State/province [42]
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Yaroslavl
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Marinus Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01963208
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Country
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Phone
0
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01963208
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