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

NCT ID: NCT01963208

Last Updated: 2023-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 405 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2016-10-31

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).

Detailed Description

This is a 2-cohort study comprised of 2 phases in each cohort. Phase 1 is a double-blind (DB) phase followed by Phase 2, an open-label phase. Cohort 1 will provide tolerability, safety, and PK information for ganaxolone 1200 milligram per day (mg/day), 1800 mg/day and placebo. Cohort 2 will investigate the efficacy, tolerability and safety of ganaxolone 1800 mg/day 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 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 treatment phase.

Conditions

Drug Resistant Partial Onset Seizure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Double Blind - Cohort 1 - Ganaxolone

1200 mg/day and 1800 mg/day + AED

Group Type: EXPERIMENTAL

ganaxolone

Intervention Type: DRUG

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

Double Blind - Cohort 1 - Placebo

Placebo + AED

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo

Open Label - Ganaxolone in Double-blind phase

1800 mg/day + AED

Group Type: EXPERIMENTAL

ganaxolone

Intervention Type: DRUG

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

Double Blind - Cohort 2 - Ganaxolone

1800 mg/day + AED

Group Type: EXPERIMENTAL

ganaxolone

Intervention Type: DRUG

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

Double Blind - Cohort 2 - Placebo

Placebo +AED

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo

Open Label - Placebo in Double-blind phase

1800 mg/day + AED

Group Type: EXPERIMENTAL

ganaxolone

Intervention Type: DRUG

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

Interventions

ganaxolone

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

Intervention Type: DRUG

Placebo

placebo

Intervention Type: DRUG

Other Intervention Names

gnx; pbo

Eligibility Criteria

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, 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

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 participant 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 times 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 participant 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Marinus Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama Epilepsy Center

Birmingham, Alabama, United States

University of Alabama at Birmingham

Birmingham, Alabama, United States

Xenoscience Inc.

Phoenix, Arizona, United States

The MORE Foundation

Sun City, Arizona, United States

Clinical Trials Inc.

Little Rock, Arkansas, United States

Neuro-Pain Medical Center, Inc

Fresno, California, United States

Neurological Research Institute

Santa Monica, California, United States

University of Colorado- Anschutz Outpatient Pavilion

Aurora, Colorado, United States

Neuroscience Consulants

Miami, Florida, United States

Medsol Clinical Research Center

Port Charlotte, Florida, United States

Consultants in Epilepsy & Neurology

Boise, Idaho, United States

Bluegrass Epilepsy Research, LLC

Lexington, Kentucky, United States

Mid-Atlantic Epilepsy Center

Bethesda, Maryland, United States

Bringham and Women's Hospital

Boston, Massachusetts, United States

Minneapolis Clinic of Neurology

Golden Valley, Minnesota, United States

The Comprehensive Epilepsy Care Center for Children and Adults

Chesterfield, Missouri, United States

Cooper Medical Center of Rowan University

Camden, New Jersey, United States

Northeast Regional Epilepsy Group

Hackensack, New Jersey, United States

Five Towns Neuroscience Research

Cedarhurst, New York, United States

Northeast Regional Epilepsy Group

Middletown, New York, United States

Winthrop University Hospital

Mineola, New York, United States

New York University Comprehensive Epilepsy Center

New York, New York, United States

Northeast Regional Epilepsy Group

New York, New York, United States

Wake Forest Health Sciences

Winston-Salem, North Carolina, United States

Ohio Clinical Research Partners, LLC

Canton, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Lynn Health Institute

Oklahoma City, Oklahoma, United States

Sooner Clinical Research

Oklahoma City, Oklahoma, United States

Jefferson Comprehensive Epilepsy Center

Philadelphia, Pennsylvania, United States

Temple University School of Medicine

Philadelphia, Pennsylvania, United States

Neurology Consultants of Dallas

Dallas, Texas, United States

Texas Epilepsy Group

Dallas, Texas, United States

Rainier Clinical Research Center, Inc.

Renton, Washington, United States

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

The Prince of Wales Hospital

Randwick, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Flinders Medical Center

Bedford Park, South Australia, Australia

St. Vincent's Hospital

Fitzroy, Victoria, Australia

The Florey Institute of Neuroscience and Mental Health

Heidelberg, Victoria, Australia

The Royal Melbourne Hospital

Parkville, Victoria, Australia

MHAT

Blagoevgrad, , Bulgaria

UMHAT Dr. Georgi Stranski Clinic of Neurology

Pleven, , Bulgaria

Medical Centre-Teodora

Rousse, , Bulgaria

Medical Center Excelsior 4

Sofia, , Bulgaria

SHATNP

Sofia, , Bulgaria

MHAT Lyulin Department of Neurology

Sofia, , Bulgaria

UMHAT Alexandrovska Clinic of Nerve Diseases

Sofia, , Bulgaria

Medical Center Ekvita Ltd

Varna, , Bulgaria

Epilepsieklinik

Bernau, , Germany

Krankenhaus Mara Epilepsie-Zentrum

Bielefeld, , Germany

Klinik fur Epileptologie

Bonn, , Germany

Neuro-Consil

Dussseldorf, , Germany

Universitatsklinikum GieBen und Marburg

Marburg, , Germany

Universitatsklin Kum Ulm

Ulm, , Germany

Novo-Med

Jaworowa, , Poland

Centrum Medycne Dendryt

Katowice, , Poland

Indywidualna Praktyka ul Narutowicza

Lublin, , Poland

Wojewodzki Szpital Specjalistyczny Oddzial

Lublin, , Poland

Fundacja Epileptologii Wiertnicza

Warsaw, , Poland

Instytut Psychiatrii i Neurologii

Warsaw, , Poland

Kazan State Medical University

Kazan', , Russia

Moscow, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Novosibirsk, , Russia

City Neurological Center

Novosibirsk, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Samara, , Russia

Yaroslavl, , Russia

Countries

United States; Australia; Bulgaria; Germany; Poland; Russia

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1042-0603

Identifier Type: -

Identifier Source: org_study_id