A Two-year Open-label Extension Study of Ganaxolone in Patients With Drug-resistant Partial-onset Seizures

Study Overview
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Brief Summary
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A follow-on, two-year open-label extension study of ganaxolone as add-on therapy in adult patients with drug-resistant partial-onset seizures

Detailed Description
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This study is a 2-year, open-label continuation for those patients benefiting from ganaxolone treatment after completing Protocol 1042-0603.

Official Title
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A follow-on, Two-year Open-label Extension Study of Ganaxolone as add-on Therapy in Adult Patients With Drug-resistant Partial-onset Seizures

Conditions
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Drug Resistant Partial Onset Seizure

Intervention / Treatment
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* Drug: ganaxolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have completed all scheduled clinical study visits in the previous protocol 1042-0603 and have shown a minimum 35% improvement in mean 28-day seizure frequency over the last three 28-day periods in study 1042-603 as compared to the baseline of study 1042-603. Subjects whose daily study drug compliance in Study 1042-0603 was 90% or greater, and for whom the investigator feels that the subject was compliant with the full dose as prescribed. Able to give informed consent in writing, or have a legally authorized representative able to do so, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures. Currently being treated and maintained with a stable regimen of 1, 2, or 3 anti-epileptic drugs (AED) at a consistent dose for one month prior to study entry. Implanted Vagus Nerve Stimulator (VNS) is permitted and will not count towards the number of concomitant AEDs. Able and willing to maintain an accurate and complete daily written seizure calendar or has a caregiver who is able and willing to maintain an accurate and complete daily written seizure calendar. Able and willing to take drug with food twice daily. Ganaxolone must be administered with food. Sexually active women of childbearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative pregnancy test at Visit 1 and at subsequent visits. Exclusion Criteria: Have any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome Experienced a Serious Adverse Event or a moderate or severe medically important adverse event judged probably or definitely related to open-label ganaxolone in the previous study, 1042-0603 Have Alanine transferase (ALT; SGPT) or Aspartate transferase (AST; SGOT) levels > 3 times upper limits of normal (ULN), or total bilirubin >1.5 time ULN during Study 1042-0603. Have a history of malignancy within the past 2 years, with the exception of basal cell carcinoma. 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. Have active suicidal plan/intent, or have had active suicidal thoughts in the past 6 months. Have a history of an actual suicide attempt in the last 5 years or more than 1 lifetime actual suicide attempt as classified by the Columbia-Suicide Severity Rating Scale (C-SSRS). Have a history of drug or alcohol abuse within the past 5 years. As with other AEDs, the use of alcohol is not advised. Are currently following or planning to follow a ketogenic diet. Current use of vigabatrin or ezogabine (retigabine; Potiga; Trobalt) is not permitted. Females who are pregnant, currently breastfeeding or planning to become pregnant during the study. Inability/unwillingness 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

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>Up to a maximum of 1800 mg/day | Drug: ganaxolone<br>* 225 mg capsules 450 mg to 900 mg 2x/day<br>* Other names: CCD 1042;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in 28-day Seizure Frequency | Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period of Study 1042-0603 (less than or equal to 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Post-baseline 28-day seizure frequency was calculated as the number of seizures in the entire treatment period divided by the number of days with available seizure data in the treatment period and multiplied by 28. Baseline was defined as the last non-missing value obtained before the first treatment in the preceding Study 1042-0603. The calculation for percent change from Baseline in 28-day seizure frequency was done as follows for each participant: post-Baseline 28-day seizure frequency minus Baseline 28-day seizure frequency whole divided by Baseline 28-day seizure frequency multiplied by 100 percent. | Baseline and at Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Showed Greater Than or Equal to 50% Reduction in 28-day Seizure Frequent From Baseline | A 50% responder is an individual whose reduction of percent change from Baseline to the end of the open label extension period in 28-day partial-onset seizure (POS) seizure frequency is greater than or equal to 50%. | Baseline and at Day 28 | 
| Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores | The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. very much improved 2. much improved 3. minimally improved 4. no change 5. minimally worse 6. much worse 7. very much worse. Higher scores indicated worse condition. Participants who showed CGI improvement at Week 104 (End of treatment) has been presented. | At Week 104 | 
| Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores | The participant is asked to rate the total improvement of their partial-onset seizures whether or not in the participant's judgment it is due entirely to drug treatment based on a 7-point scale using the markers very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse (1 = very much improved; 7 = very much worse). Higher scores indicated worse condition. Participants who showed PGI improvement at Week 104 (End of treatment) has been presented. | At Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Partial Onset Seizures, complex partial seizures, simple partial seizures, anticonvulsant, ganaxolone, neurosteroid, Marinus, epilepsy