Clinical trial NCT00465517 (phase 2, status: completed)
Conditions: partial epilepsy, catamenial epilepsy
ICD codes: G40.111, G40.119, G40.211, G40.219, G40.101, G40.109, G40.201
Drugs: ganaxolone
SMILES: [H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])C[C@](C)(O)CC[C@]12C
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), subjects
             should have a documented seizure frequency of ≥ 3CPS per 4 weeks on average.

          -  Subjects should not be seizure free for more than 28 consecutive days during treatment
             with a stable dose of AEDs [Note: Subjects 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 subject 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.]

               -  Subjects 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: Subjects 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 subjects who are not sexually active, abstinence is an acceptable form
             of birth control and serum β-HCG must be tested per protocol.

          -  Subjects with a history of depression who are stable an dmay 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: Subjects 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:

               -  Subjects 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 subject 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.

          -  Subject 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.