Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures and Open-label Extension

This is an interventional treatment trial for Drug Resistant Partial Onset Seizure focused on measuring partial onset seizures, complex partial seizures, simple partial seizures, anticonvulsant, ganaxolone, neurosteroid, Marinus, epilepsy Read More

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, subjects 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 subject 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 time 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 subject 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