Open-label Extension to Protocol 1042-0600

Sponsor

Marinus Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00512317

Collaborator

(none)

125

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Epilepsies, Partial	Drug: ganaxolone	Phase 2

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.

The study consists of 13 visits over 108 (+or-2) weeks.

Study Design

Study Type:

Interventional

Actual Enrollment :

125 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2007

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ganaxolone active experimental drug	Drug: ganaxolone liquid suspension dosed tid

Arm

Intervention/Treatment

Experimental: ganaxolone

active experimental drug

Drug: ganaxolone

liquid suspension dosed tid

Outcome Measures

Primary Outcome Measures

Change in weekly seizure frequency (including POS with or without secondary generalization, but not non-motor SPS)at study end compared to baseline at beginning of the double-blind study (1042-0600) [26-32 weeks]

Secondary Outcome Measures

Responder rate. Responder is defined as patients experiencing ≥50% of reduction in weekly seizure frequency at study end from the baseline [26-32 weeks]
Number of seizure-free subjects and seizure-free rate [26-32 weeks]
The weekly seizure frequencies for each seizure subtype: POS with or without secondary generalization, but not non-motor SPS [26-32 weeks]
Seizure severity and quality of life surveys [26 weeks]
Change in rate of seizures in catamenial epilepsy [26-32 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 69 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects 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.
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.
Male or female, 18 to 69 years of age (inclusive). [Note: Subjects 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) without 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 diary throughout the course of the study.
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 subjects who are not sexually active, abstinence is an acceptable form of birth control and qualitative serum βHCG pregnancy tests must be tested per protocol.
Subjects with a history of depression must be stable and may be taking one antidepressant medication

Exclusion Criteria

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, neoplasm, 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 in1042-0600 study.
Clinically unstable psychiatric disorder within the last 2 years.
Suicide attempt within the last 5 years or current significant suicidal ideation.
History of psychosis within the last 5 years.
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 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.
A history of chronic noncompliance with drug regimens.
Females who are currently breastfeeding.
Exposure to any other investigational drug within 30 days prior to randomization in 1042-0600 study.
Aspartate transaminase (AST) or alanine transaminase (ALT) levels > 3 times the upper limit of normal (ULN) at screening.
Subject has history of repetitive seizures within the 12-month period preceding study entry where the individual seizures cannot be counted.
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	Birmingham	Alabama	United States	35294-0021
2	Barrow Neurological Institute	Phoenix	Arizona	United States	85013
3	Arkansas Epilepsy Program	Little Rock	Arkansas	United States	72205
4	University of Southern California Adult Comprehensive Epilepsy Center	Los Angeles	California	United States	90033
5	University of California-Davis	Sacramento	California	United States	95817
6	Anchutz Outpatient Pavillion Neurosciences Clinic/ University of Colorado Hospital	Aurora	Colorado	United States	80010-0045
7	Yale University School of Medicine	New Haven	Connecticut	United States	06520
8	University of Florida McKnight Brain Institute	Gainesville	Florida	United States	32610-0236
9	Intercoastal Neurology	Sarasota	Florida	United States	34232
10	Emory HealthCare	Atlanta	Georgia	United States	30322
11	Southern Illinois University Medical Center	Springfield	Illinois	United States	62702
12	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
13	University of Kentucky, Dept. of Neurology	Lexington	Kentucky	United States	40536
14	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland	United States	20817
15	2799 West Grand blvd. CFP 071	Detroit	Michigan	United States	48202
16	Minnesota Epilepsy Group, PA	Saint Paul	Minnesota	United States	55102-2383
17	Comprehensive Epilepsy Care Center for Children and Adults	Chesterfield	Missouri	United States	63017
18	Neurosciences Institute at Albany Medical Center	Albany	New York	United States	12208
19	SUNY Upstate Medical University	Syracuse	New York	United States	13210
20	Ohio State University Medical Center	Columbus	Ohio	United States	43210
21	Riddle Health Care Center for Neuroscience	Media	Pennsylvania	United States	19063
22	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
23	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
24	Neurological Clinic of Texas, P.A.	Dallas	Texas	United States	75230
25	Virginia Commonwealth University	Richmond	Virginia	United States	23298