Open-label Extension to Protocol 1042-0600

Study Overview
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Brief Summary
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To allow open-label extension to patients who have completed Protocol 1042-0600.

Detailed Description
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This is an open-label study evaluating efficacy and safety of ganaxolone treatment in adults with partial onset epilepsy with or without secondary generalizations.

Official Title
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An Open-label Extension Study to Evaluate the Safety, Tolerability, and Efficacy of Ganaxolone as add-on Therapy in Adult Patients With Epilepsy Consisting of Uncontrolled Partial-onset Seizures.

Conditions
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Epilepsies, Partial

Intervention / Treatment
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* Drug: ganaxolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have completed all scheduled clinical study visits in the previous protocol 1042-0600 and have been deemed eligible (no major adverse events thought to be drug related) by the Investigator. Diagnosis of epilepsy with CPS with or without secondarily generalized seizures according to the International League Against Epilepsy [ILAE] Classification of Epileptic Seizures (1981). Diagnosis should have been established by clinical history and computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain to rule out progressive structural lesions and electroencephalogram (EEG) or video EEG with results consistent with partial-onset epilepsy. 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) without 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 diary throughout the course of the study. Sexually active women of childbearing potential must be using a medically acceptable method of birth control and have a negative qualitative serum beta-human chorionic growth hormone (beta HCG) pregnancy test result from a blood 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 (e.g., a spermicidal cream) is acceptable. In participants who are not sexually active, abstinence is an acceptable form of birth control and qualitative serum βHCG pregnancy tests must be tested per protocol. Participants with a history of depression must be stable and may be taking one antidepressant 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, neoplasm, 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 in 1042-0600 study. Clinically unstable psychiatric disorder within the last 2 years. Suicide attempt within the last 5 years or current significant suicidal ideation. History of psychosis within the last 5 years. 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 participant 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 women of childbearing potential (WCBP) who are unwilling to use a double-barrier method and establish that they are currently not pregnant by submitting to a serum pregnancy test. A history of chronic noncompliance with drug regimens. Females who are currently breastfeeding. Exposure to any other investigational drug within 30 days prior to randomization in 1042-0600 study. Aspartate transaminase (AST) or alanine transaminase (ALT) levels > 3 times the upper limit of normal (ULN) at screening. 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 during the entire clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ganaxolone<br>active experimental drug | Drug: ganaxolone<br>* liquid suspension dosed tid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117 | Percent Change in weekly seizure frequency by treatment group compared to Baseline at the beginning of the double-blind study 1042-0600 is presented. Weekly seizure frequency included partial-onset seizures (POS) with or without secondary generalization, but not non-motor simple partial seizure (SPS) during Weeks 1 through Week 117. Baseline was defined as the Day 0 assessment before study drug infusion of the double-blind study 1042-0600. | Baseline (Day 0) and Week 1 through Week 117 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Responders During Weeks 1 Through 117 | Responders were defined as participants experiencing ≥50% of reduction in mean weekly seizure frequency from the Baseline. Baseline was defined as the Day 0 assessment before study drug infusion of the double-blind study 1042-0600. | Baseline (Day 0) and Week 1 through Week 117 | 
| Number of Seizure-free Days During Weeks 1 Through 117 | Average number of seizure-free days per week for a given period was calculated as follows: (Total number of days with no seizures of any type during that period / number of days with seizure diary in that period) multiplied by 7. | Week 1 through Week 117 | 
| Number of Seizure-free Participants | Number of Seizure-free participants is presented. | Day 1 through Day 224 (Week 32) | 
| Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire | QOLIE-31 was a survey of health-related QOL for adults with epilepsy and evaluated how much distress the participant feels about problems and worries related to epilepsy. It included 38 items grouped into eight multi-item subscales - Energy/Fatigue, Emotional Well-Being, Daily Activities/Social Functioning, Cognitive Functioning, Medication Effect, Seizure Worry, Overall Quality of Life (QoL) and Distress. The subscale scores and the total score were calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100; higher scores indicated better function. Baseline was defined as the last non-missing observation prior to the first dose in double-blind study 1042-0600. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. | Baseline (Day 0) and up to Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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partial onset epilepsy, adult epilepsy, partial seizures, anticonvulsant, catamenial epilepsy, adult partial onset epilepsy