Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures, With Long-term Open-label Extensio
- Conditions
- Drug-Resistant Epilepsy with Partial-Onset SeizuresMedDRA version: 19.0 Level: PT Classification code 10015037 Term: Epilepsy System Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2014-004363-21-DE
- Lead Sponsor
- Marinus Pharmaceuticals, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 405
1. Written consent.
2. Willing to participate for the full term of 9 or 14-week double blind phase and willing to enter into the open-label phase.
3. Male/Female outpatients >18 years of age.
4. Confident diagnosis of drug-resistant epilepsy with POS with or without secondary generalization (classified according to International League Against Epilepsy Guidelines [Guy, 1981] and as determined by secondary review by the Epilepsy Consortium) for =2 years and is having POS despite having been treated in the past with =2 approved anti-epilepsy drugs (AEDs) either alone or in combination at adequate doses for a sufficient length of time in the opinion of the investigator. Diagnosis should have been established by clinical history, electroencephalogram (EEG) or video EEG with results consistent with partialonset epilepsy, and computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain to rule out progressive structural lesions within the last 10 years.
5. Based on documented history of POS, the investigator judges that the subject is likely to have 3 or more POS* during any 4-week period prior to study treatment, i.e., rarely falls below that threshold with usual fluctuations. Further, the pattern of seizures makes it unlikely the subject will have 21 seizure-free days in any 4-week period prior to study treatment.
* POS includes complex partial seizures [CPS], and simple partial seizures [SPS] with motor expression. Partial seizures may be seizures secondarily generalized [SGTC]. Subjects who only have simple partial seizures without any observable motor component will NOT be eligible to participate in this study.
6. Currently being treated and maintained with a stable regimen of 1, 2, or 3 AEDs for =1 month prior to the screening visit, without a foreseeable change in dosing for the duration of the double-blind phase of the study (AEDs may be adjusted during the open-label phase of the study).
a. Barbituates: If the subject is taking barbiturates (e.g., phenobarbital), the dose of the barbiturate must have been stable for =3 months prior to the
screening visit.
b. Vagus Nerve Stimulator (VNS): VNS will not be counted towards the number of concomitant AEDs. Subjects with surgically implanted VNS
will be allowed to enter the study provided that all of the following conditions are met:
i. The VNS has been in place for =1 year prior to the screening visit
ii. The settings must have remained constant for =3 months prior to the screening visit and remain constant throughout the study
iii. The battery is expected to last for the duration of DB Phase I (9 or 14 weeks) of the study
c. Benzodiazepines: The chronic use of a benzodiazepine as a concurrent AED is permitted as long as the dose has been stable for =1 month prior to the screening visit and remains constant throughout the study. See Section9.4.10 for use of benzodiazepines for seizure rescue or for other
indications.
d. Felbamate: The use of felbamate is allowed provided that the subject has been maintained on a stable dose of felbamate for >18 months, and has had stable liver function (AST/ALT) and hematology during the course of treatment, and is expected to remain constant throughout the study.
1. Have had previous exposure to ganaxolone.
2. Known sensitivity or allergy to any component in the study drug, progesterone, or other related steroid compounds.
3. Exposure to any investigational drug or device <30 days prior to screening, or plans to take another investigational drug at any time during the study.
4. Time of onset of epilepsy treatment <2 years prior to enrollment
5. Have generalized epilepsy, such as Lennox-Gastaut syndrome, juvenile myoclonic epilepsy, absence epilepsy, or non-epileptic seizures within the last 12- month period prior to study entry.
6. Have less than 3 POS seizures in a 28-day period or more than 21 consecutive seizure-free days during the 8-week baseline period.
7. Have only simple partial seizures without any observable motor component.
8. Have innumerable seizures or status epilepticus within the last 12-months prior to screening.
9. Have more than 100 POS total (complex partial seizures [CPS] only + simple partial seizures [SPS] with motor (both types with or without secondary generalized tonic-clonic seizures [SGTC]) per each 4-week baseline period.
10. 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.
11. Current use of vigabatrin is not permitted, as well as prior use of vigabatrin without stable visual fields tested prior to screening. If used during the last 12 months two visual fields tests are required.
12. Current use of ezogabine (retigabine; Potiga; Trobalt) is not permitted. Subjects who may have used this agent in the past should have been off this medication for at least 3 months prior to screening and should have had a documented normal fundoscopic exam by an ophthalmologist.
13. Are planning surgery, or to be evaluated for surgery, during the 9 or 14-week double blind phase to control seizures including those subjects who are considering implantation of a VNS device.
14. Are suffering from acute or progressive neurological disease, moderate or severe psychiatric disease, or severe mental abnormalities that are likely to require changes in pharmacotherapy during the 9 or 14-week double blind portion of the study or interfere with the objectives of the study or the ability to adhere to the protocol requirements.
15. Have active suicidal plan/intent, or have had active suicidal thoughts in the past 6 months.
16. 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).
17. Have a positive urine drug screen at Screening or meet criteria for current or historical Substance Use Disorder (DSM-V criteria) within the past 5 years. As with other AEDs, the use of alcohol is not advised.
18. 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, including but not limited to: clinically significant cardiac, renal, pulmonary, gastrointestinal, hematologic or hepatic conditions; or a
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method