Drug Resistant Partial Onset SeizurePhase 3NCT01963208
Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures and Open-label Extension
A Phase 3 study testing ganaxolone in people with Drug Resistant Partial Onset Seizure, run by Marinus Pharmaceuticals at 71 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug Resistant Partial Onset Seizure
- What is being tested?
- ganaxolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 405 participants
- Where
- 71 sitesin 6 countries
- Study dates
- Oct 2013to Oct 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
71 sites in 6 countries.
71 sites in 6 countries
United States33 sites
University of Colorado- Anschutz Outpatient Pavilion
Aurora, Colorado, 80045
Mid-Atlantic Epilepsy Center
Bethesda, Maryland, 20817
University of Alabama Epilepsy Center
Birmingham, Alabama, 35294-3280
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Consultants in Epilepsy & Neurology
Boise, Idaho, 83702
Bringham and Women's Hospital
Boston, Massachusetts, 02115
Cooper Medical Center of Rowan University
Camden, New Jersey, 08103
Ohio Clinical Research Partners, LLC
Canton, Ohio, 44718
Five Towns Neuroscience Research
Cedarhurst, New York, 11516
The Comprehensive Epilepsy Care Center for Children and Adults
Chesterfield, Missouri, 63017
Ohio State University
Columbus, Ohio, 43221
Neurology Consultants of Dallas
Dallas, Texas, 75231
Texas Epilepsy Group
Dallas, Texas, 75251
Neuro-Pain Medical Center, Inc
Fresno, California, 93710
Minneapolis Clinic of Neurology
Golden Valley, Minnesota, 55422
Northeast Regional Epilepsy Group
Hackensack, New Jersey, 07601
Bluegrass Epilepsy Research, LLC
Lexington, Kentucky, 40504
Clinical Trials Inc.
Little Rock, Arkansas, 72205
Neuroscience Consulants
Miami, Florida, 33176
Northeast Regional Epilepsy Group
Middletown, New York, 10941
Winthrop University Hospital
Mineola, New York, 11501
New York University Comprehensive Epilepsy Center
New York, New York, 10016
Northeast Regional Epilepsy Group
New York, New York, 10017
Lynn Health Institute
Oklahoma City, Oklahoma, 73112
Sooner Clinical Research
Oklahoma City, Oklahoma, 73112
Jefferson Comprehensive Epilepsy Center
Philadelphia, Pennsylvania, 19107
Temple University School of Medicine
Philadelphia, Pennsylvania, 19140
Xenoscience Inc.
Phoenix, Arizona, 85004
Medsol Clinical Research Center
Port Charlotte, Florida, 33952
Rainier Clinical Research Center, Inc.
Renton, Washington, 98057
Neurological Research Institute
Santa Monica, California, 90404
The MORE Foundation
Sun City, Arizona, 85351
Wake Forest Health Sciences
Winston-Salem, North Carolina, 27157
Russia11 sites
Kazan State Medical University
Kazan', 420064
Study site
Moscow, 107150
Study site
Moscow, 117049
Study site
Nizhny Novgorod, 603163
Study site
Novosibirsk, 630054
City Neurological Center
Novosibirsk, 630091
Study site
Saint Petersburg, 192019
Study site
Saint Petersburg, 194291
Study site
Saint Petersburg
Study site
Samara, 443095
Study site
Yaroslavl, 150030
Bulgaria8 sites
MHAT
Blagoevgrad, 2700
UMHAT Dr. Georgi Stranski Clinic of Neurology
Pleven, 5800
Medical Centre-Teodora
Rousse, 7000
Medical Center Excelsior 4
Sofia, 1000
SHATNP
Sofia, 1113
MHAT Lyulin Department of Neurology
Sofia, 1336
UMHAT Alexandrovska Clinic of Nerve Diseases
Sofia, 1431
Medical Center Ekvita Ltd
Varna, 9000
Australia7 sites
Flinders Medical Center
Bedford Park, South Australia, 5042
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
St. Vincent's Hospital
Fitzroy, Victoria, 3065
The Florey Institute of Neuroscience and Mental Health
Heidelberg, Victoria, 3084
The Royal Melbourne Hospital
Parkville, Victoria, 3050
The Prince of Wales Hospital
Randwick, New South Wales, 2031
Westmead Hospital
Westmead, New South Wales, 2145
Germany6 sites
Epilepsieklinik
Bernau, 16321
Krankenhaus Mara Epilepsie-Zentrum
Bielefeld, 33617
Klinik fur Epileptologie
Bonn, 53105
Neuro-Consil
Dussseldorf, 40212
Universitatsklinikum GieBen und Marburg
Marburg, 35043
Universitatsklin Kum Ulm
Ulm, 89081
Poland6 sites
Novo-Med
Jaworowa
Centrum Medycne Dendryt
Katowice
Indywidualna Praktyka ul Narutowicza
Lublin
Wojewodzki Szpital Specjalistyczny Oddzial
Lublin
Fundacja Epileptologii Wiertnicza
Warsaw
Instytut Psychiatrii i Neurologii
Warsaw
About this study
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
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).
Read the 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.
- Conditions
- Drug Resistant Partial Onset Seizure
- Being tested
- ganaxolone, Placebo
- Keywords
- partial onset seizures, complex partial seizures, simple partial seizures, anticonvulsant, ganaxolone, neurosteroid, Marinus, epilepsy
- Medical subject headings
- Seizures, Epilepsies, Partial, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ganaxoloneDrug
Also called gnx
200 mg and 225 mg capsules; target dose 1800 mg/day dosed 900mg 2x/day
PlaceboDrug
Also called pbo
placebo
| Study group | Role | What they receive |
|---|---|---|
| Double Blind - Cohort 1 - Ganaxolone | Experimental | 1200 mg/day and 1800 mg/day + AED Receives: Drug: ganaxolone |
| Double Blind - Cohort 1 - Placebo | Placebo comparator | Placebo + AED Receives: Drug: Placebo |
| Open Label - Ganaxolone in Double-blind phase | Experimental | 1800 mg/day + AED Receives: Drug: ganaxolone |
| Double Blind - Cohort 2 - Ganaxolone | Experimental | 1800 mg/day + AED Receives: Drug: ganaxolone |
| Double Blind - Cohort 2 - Placebo | Placebo comparator | Placebo +AED Receives: Drug: Placebo |
| Open Label - Placebo in Double-blind phase | Experimental | 1800 mg/day + AED Receives: Drug: ganaxolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and Week 14
Secondary outcomes (15)
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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%.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionMay 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Drug Resistant Partial Onset SeizureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 405 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marinus Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01963208
- Sponsor's protocol ID
- 1042-0603
- Status last verified
- Jan 2023
- First submitted
- 11 Oct 2013
- Last updated
- 14 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01963208
- Acronym / sponsor ID
- 1042-0603
- Conditions
- Drug Resistant Partial Onset Seizure
- Keywords
- partial onset seizures, complex partial seizures, simple partial seizures, anticonvulsant, ganaxolone, neurosteroid, Marinus, epilepsy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 405 participants (actual)
- Lead sponsor
- Marinus PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- May 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 16 Oct 2013 (estimated)
- Results
- Posted 14 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Double Blind - Cohort 1 - Ganaxolone | Experimental | Drug: ganaxolone1200 mg/day and 1800 mg/day + AED |
| Double Blind - Cohort 1 - Placebo | Placebo comparator | Drug: PlaceboPlacebo + AED |
| Open Label - Ganaxolone in Double-blind phase | Experimental | Drug: ganaxolone1800 mg/day + AED |
| Double Blind - Cohort 2 - Ganaxolone | Experimental | Drug: ganaxolone1800 mg/day + AED |
| Double Blind - Cohort 2 - Placebo | Placebo comparator | Drug: PlaceboPlacebo +AED |
| Open Label - Placebo in Double-blind phase | Experimental | Drug: ganaxolone1800 mg/day + AED |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ganaxoloneAlso: gnx200 mg and 225 mg capsules; target dose 1800 mg/day dosed 900mg 2x/day | Drug | Double Blind - Cohort 1 - Ganaxolone, Double Blind - Cohort 2 - Ganaxolone, Open Label - Ganaxolone in Double-blind phase, Open Label - Placebo in Double-blind phase |
| PlaceboAlso: pboplacebo | Drug | Double Blind - Cohort 1 - Placebo, Double Blind - Cohort 2 - Placebo |
Primary outcome
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
Time frame: Baseline and Week 14
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).
15 secondary outcomes
Double Blind: Cohort 2: Number of Participants With ≥50% Responder Rate During Titration + Maintenance Period
Time frame: 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
Time frame: Baseline and Week 14
Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 14
Time frame: At Week 14
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Maintenance Period
Time frame: Baseline and Week 2 to Week 14
Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
Time frame: Baseline and Week 14
Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Maintenance Period
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Week 2 to Week 14
Double Blind: Cohort 2: Percentage of Seizure Free Participants During the Maintenance Period
Time frame: 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
Time frame: Up to Week 14
Double Blind: Cohort 2: Longest Percent of Time Spent Seizure-free During Titration + Maintenance Period
Time frame: 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
Time frame: 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
Time frame: Week 8 and Week 14
Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 8
Time frame: At Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
71 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ganaxolone in people with Drug Resistant Partial Onset Seizure, run by Marinus Pharmaceuticals at 71 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in United States, Russia, Bulgaria, Australia, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period (time frame: Baseline and Week 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2023.