Clincosm LogoSign in Get a demo

Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures and Open-label Extension

Sponsor
Marinus Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01963208
Collaborator
(none)
405
Enrollment
71
Locations
2
Arms
36
Duration (Months)
5.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study will evaluate the effectiveness and safety of an investigational drug-ganaxolone - on partial seizure frequency in adults with epilepsy taking a maximum of 3 antiepileptic medications (AEDs).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a 2-cohort study comprised of 2 phases in each cohort. Phase 1 is a double-blind phase followed by Phase 2, an open-label phase. Cohort 1 will provide tolerability, safety, and PK information for ganaxolone 1200mg/d, 1800mg/d and placebo. Cohort 2 will investigate the efficacy, tolerability and safety of ganaxolone 1800mg/d compared to placebo. Cohort 1 (N= approximately 50) will enroll into a 67-week study comprised of a 4-week prospective baseline period plus 4 week retrospective baseline followed by two treatment phases: a 9-week randomized DB placebo-controlled treatment phase followed by a 52-week open label (OL) treatment phase. Cohort 2 (N=150) will enroll into a 72-week study comprised of a 8-week prospective baseline period followed by two treatment phases: a 14-week randomized DB placebo-controlled treatment phase followed by a 52-week open label (OL) treatment phase.

Study Design

Study Type:
Interventional
Actual Enrollment :
405 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Double Blind, Randomized, Placebo-Controlled Trial to Determine the Efficacy and Safety of Ganaxolone as Adjunctive Therapy for Adults With Drug-Resistant Partial-Onset Seizures Followed by Long-term Open-Label Treatment
Study Start Date :
Oct 1, 2013
Actual Primary Completion Date :
May 1, 2016
Actual Study Completion Date :
Oct 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: ganaxolone

active

Drug: ganaxolone
200 mg and 225 mg capsules; target dose 1800 mg/day dosed 900mg 2x/day
Other Names:
  • gnx

    		•
    Placebo Comparator: Placebo

    placebo, non-active

    Drug: Placebo
    placebo
    Other Names:
  • pbo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage change in seizure frequency per 28 days in the double blind period relative to baseline [14 wks (cohort 2)]

    Secondary Outcome Measures

    1. Change in seizure frequency per 28 days [9 wks (Cohort 1), 14 wks (Cohort 2) and 52 weeks (both)]

    2. Proportion of responders experiencing a ≥50% reduction from baseline to the end of the period, in total partial seizure frequency per 28 days [9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both)]

    3. Proportion of seizure free subjects [9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both]

    4. Clinical Global Impression of change [9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both]

    5. Patient Global Impression of change [9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both]

    6. Change in the number of seizure-free days [9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Able to give informed consent in writing, or have a legally authorized representative able to do so

    • Willing to enter and participate for the full term of the double blind phase and willing to enter into the open-label phase

    • Male or female outpatients > 18 years of age

    • Have a confident diagnosis of drug-resistant epilepsy with partial-onset seizures (POS), with or without secondary generalization, for ≥2 years. Have residual POS despite having been treated in the past with at least 2 approved anti-epilepsy drugs (AEDs) either alone or in combination

    • Based on history, subjects would be anticipated to have at least 3 POS during each 4-week Baseline period and unlikely to have 21 or more consecutive POS-free days

    • Currently being treated and maintained with a stable regimen of 1, 2, or 3 AEDs

    • Able and willing to maintain daily seizure calendar

    • Able and willing to take drug with food twice daily

    • Sexually active women of childbearing potential must use acceptable birth control and have a negative pregnancy test at all visits

    Exclusion Criteria:

    • Have had previous exposure to ganaxolone

    • Known sensitivity or allergy to any component in the study drug, progesterone, or other related steroid compounds

    • 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

    • Time of onset of epilepsy treatment < 2 years prior to enrollment

    • 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

    • Have less than 3 POS seizures in a 28-day period or more than 21 consecutive seizure-free days during the Baseline period

    • Have only simple partial seizures without any observable motor component

    • Have innumerable seizures or status epilepticus within the last 12-months prior to screening

    • Have more than 100 POS per 4-week Baseline period

    • Have 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

    • Current use of vigabatrin is not permitted. If prior use of vigabatrin, must have documented stable visual fields

    • Current use of ezogabine is not permitted. If prior use, must have been off the medication for at least 3 months prior to screening and have had documented normal fundoscopic exam by ophthalmologist

    • Are planning surgery, or to be evaluated for surgery, during the double blind phase to control seizures including VNS implantation

    • Are suffering from acute or progressive neurological disease, moderate or severe psychiatric disease, or severe mental abnormalities that are likely to require changes in drug therapy during the double blind portion of the study or interfere with the objectives of the study or the ability to adhere to the protocol requirements

    • Have a history of an actual suicide attempt in the last 5 years or more than 1 lifetime suicide attempt

    • 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.

    • 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

    • Have elevated ALT (SGPT) or AST (SGOT) greater than 3 times upper limits of normal, or total bilirubin greater than 1.5 time ULN

    • Have a history of malignancy within the past 2 years, with the exception of basal cell carcinoma

    • Are currently following or planning to follow a ketogenic diet

    • Use of dietary supplements or herbal preparations are not permitted if subject has been using them consistently for less than 6 months prior to screening, or does not plan on remaining on stable doses for the duration of the double blind phase. Use of St. John's Wort is not permitted

    • Females who are pregnant, currently breastfeeding or planning to become pregnant during the duration of the study

    • A history of chronic noncompliance with drug regimens

    • Inability to withhold grapefruit and grapefruit juice from diet during the entire clinical trial

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama Epilepsy Center Birmingham Alabama United States 35294-3280
    2 University of Alabama at Birmingham Birmingham Alabama United States 35294
    3 Xenoscience Inc. Phoenix Arizona United States 85004
    4 The MORE Foundation Sun City Arizona United States 85351
    5 Clinical Trials Inc. Little Rock Arkansas United States 72205
    6 Neuro-Pain Medical Center, Inc Fresno California United States 93710
    7 Neurological Research Institute Santa Monica California United States 90404
    8 University of Colorado- Anschutz Outpatient Pavilion Aurora Colorado United States 80045
    9 Neuroscience Consulants Miami Florida United States 33176
    10 Medsol Clinical Research Center Port Charlotte Florida United States 33952
    11 Consultants in Epilepsy & Neurology Boise Idaho United States 83702
    12 Bluegrass Epilepsy Research, LLC Lexington Kentucky United States 40504
    13 Mid-Atlantic Epilepsy Center Bethesda Maryland United States 20817
    14 Bringham and Women's Hospital Boston Massachusetts United States 02115
    15 Minneapolis Clinic of Neurology Golden Valley Minnesota United States 55422
    16 The Comprehensive Epilepsy Care Center for Children and Adults Chesterfield Missouri United States 63017
    17 Cooper Medical Center of Rowan University Camden New Jersey United States 08103
    18 Northeast Regional Epilepsy Group Hackensack New Jersey United States 07601
    19 Five Towns Neuroscience Research Cedarhurst New York United States 11516
    20 Northeast Regional Epilepsy Group Middletown New York United States 10941
    21 Winthrop University Hospital Mineola New York United States 11501
    22 New York University Comprehensive Epilepsy Center New York New York United States 10016
    23 Northeast Regional Epilepsy Group New York New York United States 10017
    24 Wake Forest Health Sciences Winston-Salem North Carolina United States 27157
    25 Ohio Clinical Research Partners, LLC Canton Ohio United States 44718
    26 Ohio State University Columbus Ohio United States 43221
    27 Lynn Health Institute Oklahoma City Oklahoma United States 73112
    28 Sooner Clinical Research Oklahoma City Oklahoma United States 73112
    29 Jefferson Comprehensive Epilepsy Center Philadelphia Pennsylvania United States 19107
    30 Temple University School of Medicine Philadelphia Pennsylvania United States 19140
    31 Neurology Consultants of Dallas Dallas Texas United States 75231
    32 Texas Epilepsy Group Dallas Texas United States 75251
    33 Rainier Clinical Research Center, Inc. Renton Washington United States 98057
    34 Royal Prince Alfred Hospital Camperdown New South Wales Australia 2050
    35 The Prince of Wales Hospital Randwick New South Wales Australia 2031
    36 Westmead Hospital Westmead New South Wales Australia 2145
    37 Flinders Medical Center Bedford Park South Australia Australia 5042
    38 St. Vincent's Hospital Fitzroy Victoria Australia 3065
    39 The Florey Institute of Neuroscience and Mental Health Heidelberg Victoria Australia 3084
    40 The Royal Melbourne Hospital Parkville Victoria Australia 3050
    41 MHAT Blagoevgrad Bulgaria 2700
    42 UMHAT Dr. Georgi Stranski Clinic of Neurology Pleven Bulgaria 5800
    43 Medical Centre-Teodora Ruse Bulgaria 7000
    44 Medical Center Excelsior 4 Sofia Bulgaria 1000
    45 SHATNP Sofia Bulgaria 1113
    46 MHAT Lyulin Department of Neurology Sofia Bulgaria 1336
    47 UMHAT Alexandrovska Clinic of Nerve Diseases Sofia Bulgaria 1431
    48 Medical Center Ekvita Ltd Varna Bulgaria 9000
    49 Epilepsieklinik Bernau Germany 16321
    50 Krankenhaus Mara Epilepsie-Zentrum Bielefeld Germany 33617
    51 Klinik fur Epileptologie Bonn Germany 53105
    52 Neuro-Consil Dussseldorf Germany 40212
    53 Universitatsklinikum GieBen und Marburg Marburg Germany 35043
    54 Universitatsklin Kum Ulm Ulm Germany 89081
    55 Novo-Med Jaworowa Poland
    56 Centrum Medycne Dendryt Katowice Poland
    57 Indywidualna Praktyka ul Narutowicza Lublin Poland
    58 Wojewodzki Szpital Specjalistyczny Oddzial Lublin Poland
    59 Fundacja Epileptologii Wiertnicza Warszawa Poland
    60 Instytut Psychiatrii i Neurologii Warszawa Poland
    61 Kazan State Medical University Kazan Russian Federation 420064
    62 Moscow Russian Federation 107150
    63 Moscow Russian Federation 117049
    64 Nizhniy Novgorod Russian Federation 603163
    65 Novosibirsk Russian Federation 630054
    66 City Neurological Center Novosibirsk Russian Federation 630091
    67 Saint Petersburg Russian Federation 192019
    68 Saint Petersburg Russian Federation 194291
    69 Saint Petersburg Russian Federation
    70 Samara Russian Federation 443095
    71 Yaroslavl Russian Federation 150030

    Sponsors and Collaborators

    • Marinus Pharmaceuticals

    Investigators

    • Study Director: Joseph Hulihan, M.D., Marinus Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Marinus Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01963208
    Other Study ID Numbers:
    • 1042-0603
    First Posted:
    Oct 16, 2013
    Last Update Posted:
    Aug 26, 2020
    Last Verified:
    Aug 1, 2020
    Keywords provided by Marinus Pharmaceuticals
    partial onset seizures
    complex partial seizures
    simple partial seizures
    anticonvulsant
    ganaxolone
    neurosteroid
    Marinus
    epilepsy
    Additional relevant MeSH terms:
    Seizures
    Ganaxolone

    Study Results

    No Results Posted as of Aug 26, 2020