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

NCT01963208 | Completed Phase 3 Results

• 1 other identifier: 1042-0603
• Study Type: interventional
• Target: 405
• Locations: 6 countries
• Sites: 71

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).

Conditions

Drug Resistant Partial Onset Seizure

Keywords

partial onset seizures; complex partial seizures; simple partial seizures; anticonvulsant; ganaxolone; neurosteroid; Marinus; epilepsy

Outcome Measures

Primary Outcomes (1)

• Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period

  Seizure frequency was based on the number of seizures per 28 days, calculated as the number of seizures over the time interval multiplied by 28 and divided by the number of days in the interval. Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period (≤ 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Baseline was defined as non-missing value of last assessment before first dose. Primary analysis was performed using a rank analysis of covariance (ANCOVA).

  Baseline and Week 14

Secondary Outcomes (15)

• Double Blind: Cohort 2: Number of Participants With ≥50% Responder Rate During Titration + Maintenance Period

  Up to Week 14

• Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Titration + Maintenance Period

  Baseline and Week 14

• Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 14

  At Week 14

• Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Maintenance Period

  Baseline and Week 2 to Week 14

• Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period

  Baseline and Week 14

Study Arms (6)

Double Blind - Cohort 1 - Ganaxolone

EXPERIMENTAL

1200 mg/day and 1800 mg/day + AED

Drug: ganaxolone

Double Blind - Cohort 1 - Placebo

PLACEBO COMPARATOR

Placebo + AED

Drug: Placebo

Open Label - Ganaxolone in Double-blind phase

EXPERIMENTAL

1800 mg/day + AED

Drug: ganaxolone

Double Blind - Cohort 2 - Ganaxolone

EXPERIMENTAL

1800 mg/day + AED

Drug: ganaxolone

Double Blind - Cohort 2 - Placebo

PLACEBO COMPARATOR

Placebo +AED

Drug: Placebo

Open Label - Placebo in Double-blind phase

EXPERIMENTAL

1800 mg/day + AED

Drug: ganaxolone

Interventions

ganaxolone DRUG

200 mg and 225 mg capsules; target dose 1800 mg/day dosed 900mg 2x/day

Also known as: gnx

Double Blind - Cohort 1 - Ganaxolone; Double Blind - Cohort 2 - Ganaxolone; Open Label - Ganaxolone in Double-blind phase; Open Label - Placebo in Double-blind phase

Placebo DRUG

placebo

Also known as: pbo

Double Blind - Cohort 1 - Placebo; Double Blind - Cohort 2 - Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, participants 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Marinus Pharmaceuticals: lead

Study Sites (71)

University of Alabama Epilepsy Center

Birmingham, Alabama, 35294-3280, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Xenoscience Inc.

Phoenix, Arizona, 85004, United States

Location

The MORE Foundation

Sun City, Arizona, 85351, United States

Location

Clinical Trials Inc.

Little Rock, Arkansas, 72205, United States

Location

Neuro-Pain Medical Center, Inc

Fresno, California, 93710, United States

Location

Neurological Research Institute

Santa Monica, California, 90404, United States

Location

University of Colorado- Anschutz Outpatient Pavilion

Aurora, Colorado, 80045, United States

Location

Neuroscience Consulants

Miami, Florida, 33176, United States

Location

Medsol Clinical Research Center

Port Charlotte, Florida, 33952, United States

Location

Consultants in Epilepsy & Neurology

Boise, Idaho, 83702, United States

Location

Bluegrass Epilepsy Research, LLC

Lexington, Kentucky, 40504, United States

Location

Mid-Atlantic Epilepsy Center

Bethesda, Maryland, 20817, United States

Location

Bringham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Minneapolis Clinic of Neurology

Golden Valley, Minnesota, 55422, United States

Location

The Comprehensive Epilepsy Care Center for Children and Adults

Chesterfield, Missouri, 63017, United States

Location

Cooper Medical Center of Rowan University

Camden, New Jersey, 08103, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

Five Towns Neuroscience Research

Cedarhurst, New York, 11516, United States

Location

Northeast Regional Epilepsy Group

Middletown, New York, 10941, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

New York University Comprehensive Epilepsy Center

New York, New York, 10016, United States

Location

Northeast Regional Epilepsy Group

New York, New York, 10017, United States

Location

Wake Forest Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Ohio Clinical Research Partners, LLC

Canton, Ohio, 44718, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

Lynn Health Institute

Oklahoma City, Oklahoma, 73112, United States

Location

Sooner Clinical Research

Oklahoma City, Oklahoma, 73112, United States

Location

Jefferson Comprehensive Epilepsy Center

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

Neurology Consultants of Dallas

Dallas, Texas, 75231, United States

Location

Texas Epilepsy Group

Dallas, Texas, 75251, United States

Location

Rainier Clinical Research Center, Inc.

Renton, Washington, 98057, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

The Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Flinders Medical Center

Bedford Park, South Australia, 5042, Australia

Location

St. Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

The Florey Institute of Neuroscience and Mental Health

Heidelberg, Victoria, 3084, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

MHAT

Blagoevgrad, 2700, Bulgaria

Location

UMHAT Dr. Georgi Stranski Clinic of Neurology

Pleven, 5800, Bulgaria

Location

Medical Centre-Teodora

Rousse, 7000, Bulgaria

Location

Medical Center Excelsior 4

Sofia, 1000, Bulgaria

Location

SHATNP

Sofia, 1113, Bulgaria

Location

MHAT Lyulin Department of Neurology

Sofia, 1336, Bulgaria

Location

UMHAT Alexandrovska Clinic of Nerve Diseases

Sofia, 1431, Bulgaria

Location

Medical Center Ekvita Ltd

Varna, 9000, Bulgaria

Location

Epilepsieklinik

Bernau, 16321, Germany

Location

Krankenhaus Mara Epilepsie-Zentrum

Bielefeld, 33617, Germany

Location

Klinik fur Epileptologie

Bonn, 53105, Germany

Location

Neuro-Consil

Dussseldorf, 40212, Germany

Location

Universitatsklinikum GieBen und Marburg

Marburg, 35043, Germany

Location

Universitatsklin Kum Ulm

Ulm, 89081, Germany

Location

Novo-Med

Jaworowa, Poland

Location

Centrum Medycne Dendryt

Katowice, Poland

Location

Indywidualna Praktyka ul Narutowicza

Lublin, Poland

Location

Wojewodzki Szpital Specjalistyczny Oddzial

Lublin, Poland

Location

Fundacja Epileptologii Wiertnicza

Warsaw, Poland

Location

Instytut Psychiatrii i Neurologii

Warsaw, Poland

Location

Kazan State Medical University

Kazan', 420064, Russia

Location

Unknown Facility

Moscow, 107150, Russia

Location

Unknown Facility

Moscow, 117049, Russia

Location

Unknown Facility

Nizhny Novgorod, 603163, Russia

Location

Unknown Facility

Novosibirsk, 630054, Russia

Location

City Neurological Center

Novosibirsk, 630091, Russia

Location

Unknown Facility

Saint Petersburg, 192019, Russia

Location

Unknown Facility

Saint Petersburg, 194291, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Samara, 443095, Russia

Location

Unknown Facility

Yaroslavl, 150030, Russia

Location

MeSH Terms

Conditions

Seizures; Epilepsies, Partial; Epilepsy

Interventions

ganaxolone

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Results Point of Contact

• Title: Marinus Clinical Trials Submission Manager
• Organization: Marinus Pharmaceuticals, Inc.

clinicaltrials@marinuspharma.com

484-801-4670

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2013
• First Posted: October 16, 2013
• Study Start: October 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: October 1, 2016
• Last Updated: February 14, 2023
• Results First Posted: February 14, 2023

Record last verified: 2023-01

Locations

RU (11); DE (6); BU (8); AU (7); PL (6); US (33)