Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures and Open-label Extension
Condition: Drug Resistant Partial Onset Seizure
MeSH terms: Seizures
Intervention: ganaxolone; Placebo
Intervention description: 200 mg and 225 mg capsules; target dose 1800 mg/day dosed 900mg 2x/day; placebo
Intervention MeSH terms: Ganaxolone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 405.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: partial onset seizures; complex partial seizures; simple partial seizures; anticonvulsant; ganaxolone; neurosteroid; Marinus; epilepsy

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).
    

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