A Randomized, Controlled Trial of Ganaxolone in Adult Uncontrolled Partial-Onset Seizures
Condition: Partial Epilepsy; Catamenial Epilepsy
MeSH terms: Epilepsy; Seizures; Epilepsies, Partial
Intervention: Ganaxolone; Placebo
Intervention description: Oral suspension 200-500 mg 3x/day; non-active placebo
Intervention MeSH terms: Ganaxolone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 147.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: Partial onset seizures; Complex-partial seizures; Anticonvulsant; Partial seizures; Catamenial 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). The study will also evaluate the effectiveness of ganaxolone in females
      with catamenial epilepsy.

      Catamenial epilepsy refers to a relationship between seizure frequency and a woman's
      menstrual cycle, where the number of seizures increases around the time of a woman's
      menstrual cycle.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Diagnosis of epilepsy with POS with or without secondary generalized seizures
             according to the International League Against Epilepsy [ILAE] Classification of
             Epileptic Seizures (1981). Diagnosis should have been established by clinical history
             and CT or MRI of the brain to rule out progressive structural lesions and EEG with
             results consistent with partial-onset epilepsy.

          -  During the 8 week baseline period preceding randomization visit (Visit 4),
             participants should have a documented seizure frequency of ≥ 3CPS per 4 weeks on
             average.

          -  Participants should not be seizure free for more than 28 consecutive days during
             treatment with a stable dose of AEDs [Note: Participants with historically
             sufficiently high seizure frequency who fall short 1 seizure in any 4 weeks period or
             with a seizure-free period > 28 consecutive days may be allowed to enter the study
             after discussion with the Medical Monitor. Prolongation of the screening period for
             questionable cases may also be allowed by the Medical Monitor.]

          -  Treatment with a stable dose of up to 3 (FDA approved) current AEDs for 1 month prior
             to screening.

          -  Maintenance of current AEDs without a change in dosing for the duration of study.

               -  Concomitant vigabatrin not permitted;

               -  Felbamate is allowed if the participant has been on felbamate for at least 18
                  months and has stable laboratory tests) for the course of the study. [Note: A
                  shorter period for stable laboratory results may be allowed by the Medical
                  Monitor, depending on the extent of dose change and the half-life of the AED.]

               -  Participants receiving treatment with a vagal nerve stimulator (VNS) may be
                  included as long as the VNS has been in place for at least 12 months prior to
                  entry into the study, the VNS battery is not due for replacement during 0600
                  subject participation, and stimulation parameters have been kept constant for 1
                  month prior to screening. VNS will be counted as 1 of the 3 concomitant AEDs.

          -  Male or female, 18 to 69 years of age (inclusive). [Note: Participants who are > 69
             years of age but are of good health condition may be allowed to enter the study after
             discussion with and approval by the Medical Monitor.]

          -  A 12-lead electrocardiogram (ECG) w/o clinically significant abnormalities.

          -  Be properly informed of the nature and risks of the study and give informed consent in
             writing, prior to entering the study.

          -  Able to participate for the full term of study.

          -  Able to keep a seizure & medication diary throughout the course of the study.

          -  Sexually active women of childbearing potential (WCBP) must be using a medically
             acceptable method of birth control and have a negative qualitative β-human chorionic
             growth hormone (β-HCG) pregnancy test result from a urine sample collected at the
             initial screening visit. A woman of childbearing potential is defined as a female who
             is biologically capable of becoming pregnant. A medically acceptable method of birth
             control includes intrauterine devices in place for at least 3 months, surgical
             sterilization, or adequate barrier methods (e.g., diaphragm and foam). An oral
             contraceptive alone is not considered adequate for the purpose of this study. Use of
             oral contraceptives in combination with another method (eg, a spermicidal cream) is
             acceptable.in participants who are not sexually active, abstinence is an acceptable
             form of birth control and serum β-HCG must be tested per protocol.

          -  Participants with a history of depression who are stable and may be taking 1
             anti-depressant medication.

        EXCLUSION CRITERIA:

          -  Presence of non-motor simple partial seizures only.

          -  History of pseudoseizures in the last 5 years.

          -  History of a primary generalized seizure in the last 5 years.

          -  Past use of vigabatrin without stable visual fields tested twice over the 12 months
             after the last dose of vigabatrin (Concomitant use of vigabatrin is not allowed).

          -  Seizures secondary to illicit drug or alcohol use, infection, neoplasia, demyelinating
             disease, degenerative neurological disease, or CNS disease deemed progressive,
             metabolic illness, or progressive degenerative disease.

          -  Status epilepticus within the last year prior to randomization.

          -  Clinically unstable psychiatric disorder within the last 2 years.

          -  Suicidal attempt within the last 5 years or current significant suicidal ideation.

          -  History of psychosis within the last 5 years. [Note: Participants who suffered a
             psychosis that can well be explained by exogenous factors may be allowed to enter the
             study after discussion with and approval by the Medical Monitor.]

          -  Current use of neuroleptics for psychosis.

          -  A significant medical or surgical condition at screening which might compromise the
             hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems or
             other conditions that would place the subject at increased risk.

          -  Known sensitivity or allergy to progesterone or related steroid compounds.

          -  History of drug use or alcohol abuse within the past 5 years.

          -  Sexually active WCBP who are unwilling to use a double-barrier method and establish
             that they are currently not pregnant by submitting to a pregnancy test.

          -  Females who are currently breastfeeding.

          -  history of chronic noncompliance with drug regimens.

          -  Exposure to any other investigational drug or device within 30 days prior to
             screening.

          -  Alanine transferase (ALT; SGPT) or Aspartate transferase (AST; SGOT) levels > 3 times
             upper limits of normal (ULN) at screening.

          -  Benzodiazepines may be used intermittently for the control of seizure clustering as a
             one time rescue up to a maximum of 4 occasions as follows:

               -  Participants who need benzodiazepines for control of seizures more than once per
                  month or more than 4 times total during the Titration and Maintenance Phases will
                  be discontinued.

               -  Once during the Titration Phase

               -  No more than once per month during the Maintenance Phase

               -  Each occasion may be a period of 24 hours, during which up to 3 doses of
                  benzodiazepine may be used.

               -  If a participant is taking a benzodiazepine chronically for epilepsy and
                  non-epilepsy conditions, it will be counted as 1 of the 3 AEDs and the dose
                  cannot be changed during the study.

          -  Participant has history of repetitive seizures within the 12-month period preceding
             study entry where the individual seizures cannot be counted.

          -  Inability to withhold grapefruit and grapefruit juice from diet for the entire
             clinical trial.