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

This study has been completed.
Sponsor:
Information provided by:
Marinus Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00465517
First received: April 24, 2007
Last updated: October 28, 2009
Last verified: October 2009
  Purpose

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.


Condition Intervention Phase
Partial Epilepsy
Catamenial Epilepsy
Drug: Ganaxolone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Ganaxolone as add-on Therapy in Adult Subjects With Epilepsy Consisting of Uncontrolled Partial-onset Seizures.

Resource links provided by NLM:


Further study details as provided by Marinus Pharmaceuticals:

Primary Outcome Measures:
  • Weekly seizure frequency, analyzed as mean weekly log-transformed seizure frequency [including POS with or without secondary generalization, but not non-motor SPS] during the Maintenance Phase (Weeks 3 to 10). [ Time Frame: 10-16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change and percent change of mean weekly seizure frequency from baseline [ Time Frame: 10-16 weeks ] [ Designated as safety issue: No ]
  • Change and percent change of weekly seizure frequency from baseline for each week after dosing [ Time Frame: 10-16 weeks ] [ Designated as safety issue: No ]
  • Responder rate. Responders are defined as patients experiencing ≥50% of reduction in mean weekly seizure frequency during the maintenance period from the baseline [ Time Frame: 10-16weeks ] [ Designated as safety issue: No ]
  • Number of seizure-free days [ Time Frame: 10-16 weeks ] [ Designated as safety issue: No ]
  • Number of seizure-free subjects and seizure-free rate [ Time Frame: 10-16 weeks ] [ Designated as safety issue: No ]
  • The weekly seizure frequencies, changes, and percent changes from baseline for each seizure subtype: POS with or without secondary generalization, but not non-motor SPS [ Time Frame: 10-16 weeks ] [ Designated as safety issue: No ]
  • Seizure severity questionnaires and quality of life surveys changes [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  • Change in rate of seizures in catamenial epilepsy [ Time Frame: 10-16 weeks ] [ Designated as safety issue: No ]
  • Weekly seizure frequency for each week after dosing. [ Time Frame: 10-16 weeks ] [ Designated as safety issue: No ]

Enrollment: 147
Study Start Date: February 2007
Study Completion Date: November 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ganaxolone Drug: Ganaxolone
Oral suspension 200-500 mg 3x/day
Placebo Comparator: non-active drug Drug: Ganaxolone
Oral suspension 200-500 mg 3x/day

Detailed Description:

Subjects will undergo

  • 8-week baseline seizure period
  • Randomization to ganaxolone or placebo
  • Dose titrate for 2 weeks followed by 8 weeks of maintenance.
  • Eligible subjects will be offered participation in the open-label extension study.
  • Those not entering open-label will undergo a 6-week dose de-escalation to gradually taper ganaxolone.
  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • 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), subjects should have a documented seizure frequency of ≥ 3CPS per 4 weeks on average.
  • Subjects should not be seizure free for more than 28 consecutive days during treatment with a stable dose of AEDs [Note: Subjects 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 subject 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.]
    • Subjects 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: 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) 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 subjects who are not sexually active, abstinence is an acceptable form of birth control and serum β-HCG must be tested per protocol.
  • Subjects with a history of depression who are stable an dmay be taking 1 anti-depressant 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, 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: Subjects 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.
  • history of chronic noncompliance with drug regimens.
  • Exposure to any other investigational drug or device within 30 days prior to screening.
  • Alanine transferase (ALT; SGPT) or Aspartate transferase (AST; SGOT) levels > 3 times upper limits of normal (ULN) at screening.
  • Benzodiazepines may be used intermittently for the control of seizure clustering as a one time rescue up to a maximum of 4 occasions as follows:

    • Subjects who need benzodiazepines for control of seizures more than once per month or more than 4 times total during the Titration and Maintenance Phases will be discontinued.
    • Once during the Titration Phase
    • No more than once per month during the Maintenance Phase
    • Each occasion may be a period of 24 hours, during which up to 3 doses of benzodiazepine may be used.
    • If a subject is taking a benzodiazepine chronically for epilepsy and non-epilepsy conditions, it will be counted as 1 of the 3 AEDs and the dose cannot be changed during the study.
  • 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 for the entire clinical trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00465517

  Show 27 Study Locations
Sponsors and Collaborators
Marinus Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Julia Tsai/ Director Clinical Operations, Marinus Pharmaceutical, Inc
ClinicalTrials.gov Identifier: NCT00465517     History of Changes
Other Study ID Numbers: 1042-0600, V 1.3
Study First Received: April 24, 2007
Last Updated: October 28, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Marinus Pharmaceuticals:
Partial onset seizures
Complex-partial seizures
Anticonvulsant
Partial seizures
Catamenial epilepsy

Additional relevant MeSH terms:
Epilepsies, Partial
Epilepsy
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on November 19, 2014