A Randomized, Controlled Trial of Ganaxolone in Adult Uncontrolled Partial-Onset Seizures

NCT00465517 | Completed Phase 2 Results

• 2 other identifiers: 1042-0600V 1.3
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 27

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). The study will also evaluate the effectiveness of ganaxolone in females with catamenial epilepsy. Catamenial epilepsy refers to a relationship between seizure frequency and a woman's menstrual cycle, where the number of seizures increases around the time of a woman's menstrual cycle.

Conditions

Partial Epilepsy; Catamenial Epilepsy

Keywords

Partial onset seizures; Complex-partial seizures; Anticonvulsant; Partial seizures; Catamenial epilepsy

Outcome Measures

Primary Outcomes (1)

• Mean Weekly Log-transformed Seizure Frequency During Weeks 1 Through 10

  Weekly seizure frequency, analyzed as mean weekly log-transformed seizure frequency \[including partial-onset seizures (POS) with or without secondary generalization, but not non-motor simple partial seizure (SPS)\] during Weeks 1 through 10.

  Week 1 through Week 10

Secondary Outcomes (15)

• Mean Weekly Log-transformed Seizure Frequency During Weeks 3 Through 10

  Week 3 through Week 10

• Change From Baseline in Mean Weekly Seizure Frequency During Weeks 1 Through 10

  Baseline and at Week 1 through Week 10

• Change From Baseline in Mean Weekly Seizure Frequency During Weeks 3 Through 10

  Baseline and at Week 3 through Week 10

• Percent Change From Baseline in Mean Weekly Seizure Frequency During Weeks 1 Through 10

  Baseline and at Week 1 through Week 10

• Percent Change From Baseline in Mean Weekly Seizure Frequency During Weeks 3 Through 10

  Baseline and at Week 3 through Week 10

Study Arms (2)

ganaxolone

EXPERIMENTAL

active study drug

Drug: Ganaxolone

non-active drug

PLACEBO COMPARATOR

placebo

Other: Placebo

Interventions

Ganaxolone DRUG

Oral suspension 200-500 mg 3x/day

ganaxolone

Placebo OTHER

non-active placebo

non-active drug

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of epilepsy with POS with or without secondary generalized seizures according to the International League Against Epilepsy \[ILAE\] Classification of Epileptic Seizures (1981). Diagnosis should have been established by clinical history and CT or MRI of the brain to rule out progressive structural lesions and EEG with results consistent with partial-onset epilepsy.
• During the 8 week baseline period preceding randomization visit (Visit 4), participants should have a documented seizure frequency of ≥ 3CPS per 4 weeks on average.
• Participants should not be seizure free for more than 28 consecutive days during treatment with a stable dose of AEDs \[Note: Participants with historically sufficiently high seizure frequency who fall short 1 seizure in any 4 weeks period or with a seizure-free period \> 28 consecutive days may be allowed to enter the study after discussion with the Medical Monitor. Prolongation of the screening period for questionable cases may also be allowed by the Medical Monitor.\]
• Treatment with a stable dose of up to 3 (FDA approved) current AEDs for 1 month prior to screening.
• Maintenance of current AEDs without a change in dosing for the duration of study.
• Concomitant vigabatrin not permitted;
• Felbamate is allowed if the participant has been on felbamate for at least 18 months and has stable laboratory tests) for the course of the study. \[Note: A shorter period for stable laboratory results may be allowed by the Medical Monitor, depending on the extent of dose change and the half-life of the AED.\]
• Participants receiving treatment with a vagal nerve stimulator (VNS) may be included as long as the VNS has been in place for at least 12 months prior to entry into the study, the VNS battery is not due for replacement during 0600 subject participation, and stimulation parameters have been kept constant for 1 month prior to screening. VNS will be counted as 1 of the 3 concomitant AEDs.
• Male or female, 18 to 69 years of age (inclusive). \[Note: Participants who are \> 69 years of age but are of good health condition may be allowed to enter the study after discussion with and approval by the Medical Monitor.\]
• A 12-lead electrocardiogram (ECG) w/o clinically significant abnormalities.
• Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study.
• Able to participate for the full term of study.
• Able to keep a seizure \& medication diary throughout the course of the study.
• Sexually active women of childbearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative qualitative β-human chorionic growth hormone (β-HCG) pregnancy test result from a urine sample collected at the initial screening visit. A woman of childbearing potential is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices in place for at least 3 months, surgical sterilization, or adequate barrier methods (e.g., diaphragm and foam). An oral contraceptive alone is not considered adequate for the purpose of this study. Use of oral contraceptives in combination with another method (eg, a spermicidal cream) is acceptable.in participants who are not sexually active, abstinence is an acceptable form of birth control and serum β-HCG must be tested per protocol.
• Participants with a history of depression who are stable and may be taking 1 anti-depressant medication.

You may not qualify if:

• Presence of non-motor simple partial seizures only.
• History of pseudoseizures in the last 5 years.
• History of a primary generalized seizure in the last 5 years.
• Past use of vigabatrin without stable visual fields tested twice over the 12 months after the last dose of vigabatrin (Concomitant use of vigabatrin is not allowed).
• Seizures secondary to illicit drug or alcohol use, infection, neoplasia, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive, metabolic illness, or progressive degenerative disease.
• Status epilepticus within the last year prior to randomization.
• Clinically unstable psychiatric disorder within the last 2 years.
• Suicidal attempt within the last 5 years or current significant suicidal ideation.
• History of psychosis within the last 5 years. \[Note: Participants who suffered a psychosis that can well be explained by exogenous factors may be allowed to enter the study after discussion with and approval by the Medical Monitor.\]
• Current use of neuroleptics for psychosis.
• A significant medical or surgical condition at screening which might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems or other conditions that would place the subject at increased risk.
• Known sensitivity or allergy to progesterone or related steroid compounds.
• History of drug use or alcohol abuse within the past 5 years.
• Sexually active WCBP who are unwilling to use a double-barrier method and establish that they are currently not pregnant by submitting to a pregnancy test.
• Females who are currently breastfeeding.

Sponsors & Collaborators

• Marinus Pharmaceuticals: lead

Study Sites (27)

University of Alabama

Birmingham, Alabama, 35294-0021, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Arkansas Epilepsy Program

Little Rock, Arkansas, 72205, United States

Location

University of Southern California Adult Comprehensive Epilepsy Center

Los Angeles, California, 90033, United States

Location

University of California-Davis

Sacramento, California, 95817, United States

Location

Anchutz Outpatient Pavillion Neurosciences Clinic/ University of Colorado Hospital

Aurora, Colorado, 80010-0045, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

University of Florida McKnight Brain Institute

Gainesville, Florida, 32610-0236, United States

Location

Intercoastal Medicine

Sarasota, Florida, 34232, United States

Location

Emory HealthCare

Atlanta, Georgia, 30322, United States

Location

Southern Illinois University Medical Center

Springfield, Illinois, 62702, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kentucky, Dept. of Neurology

Lexington, Kentucky, 40536, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

2799 West Grand blvd. CFP 071

Detroit, Michigan, 48202, United States

Location

Minnesota Epilepsy Group, PA

Saint Paul, Minnesota, 55102-2383, United States

Location

Comprehensive Epilepsy Care Center for Children and Adults

Chesterfield, Missouri, 63017, United States

Location

Overlook Hospital and Hackensack Medical Center

Hackensack, New Jersey, 07601, United States

Location

Neurosciences Institute at Albany Medical Center

Albany, New York, 12208, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Riddle Health Care Center for Neuroscience

Media, Pennsylvania, 19063, United States

Location

Drexel University / Hahneman Hospital

Philadelphia, Pennsylvania, 19102, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Vanderbilt University Medical Ctr

Nashville, Tennessee, 37232, United States

Location

Neurological Clinic of Texas, P.A.

Dallas, Texas, 75230, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• Maguire MJ, Nevitt SJ. Treatments for seizures in catamenial (menstrual-related) epilepsy. Cochrane Database Syst Rev. 2021 Sep 16;9(9):CD013225. doi: 10.1002/14651858.CD013225.pub3.

  PMID: 34528245 DERIVED

Related Links

• information about ganaxolone

MeSH Terms

Conditions

Epilepsies, Partial; Seizures

Interventions

ganaxolone

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Overall count of AEs provided is associated with 'at least 1 AE'.

Results Point of Contact

• Title: Marinus
• Organization: Marinus Pharmaceuticals, Inc.

clinicaltrials@marinuspharma.com

(484) 801-4670

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: April 24, 2007
• First Posted: April 25, 2007
• Study Start: February 1, 2007
• Primary Completion: October 1, 2008
• Study Completion: November 1, 2008
• Last Updated: March 15, 2023
• Results First Posted: March 15, 2023

Record last verified: 2023-02

Locations

US (27)