Clinical trial NCT02519439: A Two-year Open-label Extension Study of Ganaxolone in Patients With Drug-resistant Partial-onset Seizures
Official title: A follow-on, Two-year Open-label Extension Study of Ganaxolone as add-on Therapy in Adult Patients With Drug-resistant Partial-onset Seizures
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Drug Resistant Partial Onset Seizure
Keywords: Partial Onset Seizures
complex partial seizures
simple partial seizures
anticonvulsant
ganaxolone
neurosteroid
Marinus
epilepsy
Lead sponsor: Marinus Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-08-11
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline in 28-day Seizure Frequency
timeFrame: Baseline and at Day 28
Secondary outcomes:
measure: Number of Participants Who Showed Greater Than or Equal to 50% Reduction in 28-day Seizure Frequent From Baseline
timeFrame: Baseline and at Day 28
measure: Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores
timeFrame: At Week 104
measure: Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores
timeFrame: At Week 104
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Neurological Research Institute
state: California
city: Lexington
country: United States
facility: Bluegrass Epilepsy Research, LLC
state: Kentucky
city: Golden Valley
country: United States
facility: Minneapolis Clinic of Neurology
state: Minnesota
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: Dallas
country: United States
facility: Texas Epilepsy Group
state: Texas
Study officials:
References: