Pilot, multicenter study to evaluate the efficacy of the ganaxolone in female children with PCDH19 Pediatric Epilepsy.
- Conditions
- PCDH19 Female Pediatric Epilepsy (FPE)MedDRA version: 18.0Level: LLTClassification code 10032062Term: Other forms of epilepsy, with intractable epilepsySystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2015-001324-36-IT
- Lead Sponsor
- Marinus Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 10
1. Have parent or legal guardian available and willing to give written informed consent, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures.
2. Female outpatients > 2 years of age and younger than 11 years of age at time of consent.
3. Have confirmed PCDH19 genetic mutation.
4. Have uncontrolled cluster seizures (approximately 10 or more seconds between seizures), lasting for one hour or more per episode, with inter-cluster episodes of not more than 6 weeks, AND/OR, non-clustered focal dyscognitive or focal convulsive seizures with a frequency =4 seizures per 28-day period during baseline.
5. Subjects should be on a stable regimen of AED medication, and generally in good health.
6. Parent or guardian is able and willing to maintain an accurate and complete daily written seizure calendar for the duration of the study.
7. Able and willing to take study medication with food, two or three times daily. Ganaxolone must be administered with food.
8. Subject must be approved to participate by Sponsor and Principal Investigator after review of medical history and baseline seizure calendars.
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
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. Have SCN1A genetic mutation.
4. Exposure to any investigational drug or device < 90 days prior to screening, or plans to participate in another drug or device trial at any time during the study.
5. 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.
6. Concurrent use of vigabatrin, tiagabine, ezogabine or finasteride is not permitted, nor use of moderate or severe inducers or inhibitors of CYP3A4/5/7. Individuals with prior use of vigabatrin must have had stable visual fields tested twice over the 12 months after the last dose of vigabatrin. A list of CYP3A4/5/7 inhibitors and inducers is included in the Appendix.
7. 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 condition that affects the absorption, distribution, metabolism or excretion of drugs.
8. Have active suicidal plan/intent, or have had active suicidal thoughts in the past 6 months or a suicide attempt in the past 3 years.
9. 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 at the baseline visit.
10. Are currently following or planning to follow a ketogenic diet.
11. Is sexually active or pregnant.
12. Unwilling to forgo grapefruit and grapefruit juice from diet during the entire clinical trial.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of open-label ganaxolone as adjunctive therapy for uncontrolled seizures in female children with PCDH19 mutation.;Secondary Objective: To evaluate the safety and tolerability of open-label ganaxolone as adjunctive therapy for uncontrolled seizures in female children with PCDH19 mutation.;Primary end point(s): Percentage change in seizure (focal dyscognitive or focal convulsive) frequency per 28 days relative to baseline.;Timepoint(s) of evaluation of this end point: 28 days from calculated baseline.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Efficacy: <br>Evaluation of inter-cluster interval calculated using daily seizure diary. <br>Seizure-free interval calculated using daily seizure diary.<br>Proportion of responders by cohort calculated using daily seizure diary. <br>Proportion of subjects whose inter-cluster interval increases by cohort calculated using daily seizure diary. <br>Time to reach baseline number of seizures (per 28 days) calculated using daily seizure diary. <br>Clinician Global Impression of Change score as assessed by questionnaire. Patient Global Impression of Change score as assessed by questionnaire.<br><br>Safety:<br>Evaluation of safety and tolerability of open-label ganaxolone as adjunctive therapy for uncontrolled seizures in female children with PCDH19 mutation, based on adverse event log and other clinical safety assessments. ;Timepoint(s) of evaluation of this end point: Efficacy:<br>26 weeks<br><br>Safety:<br>30 weeks