A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Ganaxolone as add-on Therapy in Adult Subjects With Epilepsy Consisting of Uncontrolled Partial-onset Seizures.
A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Ganaxolone as add-on Therapy in Adult Subjects With Epilepsy Consisting of Uncontrolled Partial-onset Seizures.
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.
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.
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:
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.
Los Angeles, California 90033, United States
Aurora, Colorado 80010-0045, United States
Chesterfield, Missouri 63017, United States