Clinical trial NCT00512317: Open-label Extension to Protocol 1042-0600
Official title: An Open-label Extension Study to Evaluate the Safety, Tolerability, and Efficacy of Ganaxolone as add-on Therapy in Adult Patients With Epilepsy Consisting of Uncontrolled Partial-onset Seizures.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epilepsies, Partial
Keywords: partial onset epilepsy
adult epilepsy
partial seizures
anticonvulsant
catamenial epilepsy
adult partial onset epilepsy
Lead sponsor: Marinus Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-08-07
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To allow open-label extension to patients who have completed Protocol 1042-0600.

Detailed description: This is an open-label study evaluating efficacy and safety of ganaxolone treatment in adults with partial onset epilepsy with or without secondary generalizations.

Eligibility criteria: Inclusion Criteria:

1. Participants who have completed all scheduled clinical study visits in the previous protocol 1042-0600 and have been deemed eligible (no major adverse events thought to be drug related) by the Investigator.
2. Diagnosis of epilepsy with CPS with or without secondarily generalized seizures according to the International League Against Epilepsy \[ILAE\] Classification of Epileptic Seizures (1981). Diagnosis should have been established by clinical history and computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain to rule out progressive structural lesions and electroencephalogram (EEG) or video EEG with results consistent with partial-onset epilepsy.
3. Male or female, 18 to 69 years of age (inclusive). \[Note: Participants who are \> 69 years of age but are of good health condition may be allowed to enter the study after discussion with and approval by the Medical Monitor.\]
4. A 12-lead electrocardiogram (ECG) without clinically significant abnormalities.
5. Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study.
6. Able to participate for the full term of study.
7. Able to keep a seizure diary throughout the course of the study.
8. Sexually active women of childbearing potential must be using a medically acceptable method of birth control and have a negative qualitative serum beta-human chorionic growth hormone (beta HCG) pregnancy test result from a blood 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 (e.g., a spermicidal cream) is acceptable. In participants who are not sexually active, abstinence is an acceptable form of birth control and qualitative serum βHCG pregnancy tests must be tested per protocol.
9. Participants with a history of depression must be stable and may be taking one antidepressant medication

Exclusion Criteria:

1. Presence of non-motor simple partial seizures only.
2. History of pseudoseizures in the last 5 years.
3. History of a primary generalized seizure in the last 5 years.
4. 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).
5. Seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive, metabolic illness, or progressive degenerative disease.
6. Status epilepticus within the last year prior to randomization in 1042-0600 study.
7. Clinically unstable psychiatric disorder within the last 2 years.
8. Suicide attempt within the last 5 years or current significant suicidal ideation.
9. History of psychosis within the last 5 years.
10. Current use of neuroleptics for psychosis.
11. 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 participant at increased risk.
12. Known sensitivity or allergy to progesterone or related steroid compounds.
13. History of drug use or alcohol abuse within the past 5 years.
14. Sexually active women of childbearing potential (WCBP) who are unwilling to use a double-barrier method and establish that they are currently not pregnant by submitting to a serum pregnancy test.
15. A history of chronic noncompliance with drug regimens.
16. Females who are currently breastfeeding.
17. Exposure to any other investigational drug within 30 days prior to randomization in 1042-0600 study.
18. Aspartate transaminase (AST) or alanine transaminase (ALT) levels \> 3 times the upper limit of normal (ULN) at screening.
19. Participant has history of repetitive seizures within the 12-month period preceding study entry where the individual seizures cannot be counted.
20. Inability to withhold grapefruit and grapefruit juice from diet during the entire clinical trial.

Primary outcomes:
measure: Percent Change From Baseline in Weekly Seizure Frequency During Weeks 1 Through 117
timeFrame: Baseline (Day 0) and Week 1 through Week 117
Secondary outcomes:
measure: Number of Responders During Weeks 1 Through 117
timeFrame: Baseline (Day 0) and Week 1 through Week 117
measure: Number of Seizure-free Days During Weeks 1 Through 117
timeFrame: Week 1 through Week 117
measure: Number of Seizure-free Participants
timeFrame: Day 1 through Day 224 (Week 32)
measure: Change From Baseline in Quality of Life in Epilepsy Inventory-31 (QOLIE-31) Questionnaire
timeFrame: Baseline (Day 0) and up to Week 104
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Epilepsy Program
state: Arkansas
city: Los Angeles
country: United States
facility: University of Southern California Adult Comprehensive Epilepsy Center
state: California
city: Sacramento
country: United States
facility: University of California-Davis
state: California
city: Aurora
country: United States
facility: Anchutz Outpatient Pavillion Neurosciences Clinic/ University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida McKnight Brain Institute
state: Florida
city: Sarasota
country: United States
facility: Intercoastal Neurology
state: Florida
city: Atlanta
country: United States
facility: Emory HealthCare
state: Georgia
city: Springfield
country: United States
facility: Southern Illinois University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky, Dept. of Neurology
state: Kentucky
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Detroit
country: United States
facility: 2799 West Grand blvd. CFP 071
state: Michigan
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group, PA
state: Minnesota
city: Chesterfield
country: United States
facility: Comprehensive Epilepsy Care Center for Children and Adults
state: Missouri
city: Albany
country: United States
facility: Neurosciences Institute at Albany Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Media
country: United States
facility: Riddle Health Care Center for Neuroscience
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Neurological Clinic of Texas, P.A.
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
References: