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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01963208
Recruitment Status : Completed
First Posted : October 16, 2013
Last Update Posted : August 26, 2020
Information provided by (Responsible Party):
Marinus Pharmaceuticals

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).

Condition or disease Intervention/treatment Phase
Drug Resistant Partial Onset Seizure Drug: ganaxolone Drug: Placebo Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 405 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double Blind, Randomized, Placebo-Controlled Trial to Determine the Efficacy and Safety of Ganaxolone as Adjunctive Therapy for Adults With Drug-Resistant Partial-Onset Seizures Followed by Long-term Open-Label Treatment
Study Start Date : October 2013
Actual Primary Completion Date : May 2016
Actual Study Completion Date : October 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Medicines Seizures

Arm Intervention/treatment
Experimental: ganaxolone
Drug: ganaxolone
200 mg and 225 mg capsules; target dose 1800 mg/day dosed 900mg 2x/day
Other Name: gnx

Placebo Comparator: Placebo
placebo, non-active
Drug: Placebo
Other Name: pbo

Primary Outcome Measures :
  1. Percentage change in seizure frequency per 28 days in the double blind period relative to baseline [ Time Frame: 14 wks (cohort 2) ]

Secondary Outcome Measures :
  1. Change in seizure frequency per 28 days [ Time Frame: 9 wks (Cohort 1), 14 wks (Cohort 2) and 52 weeks (both) ]
  2. Proportion of responders experiencing a ≥50% reduction from baseline to the end of the period, in total partial seizure frequency per 28 days [ Time Frame: 9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both) ]
  3. Proportion of seizure free subjects [ Time Frame: 9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both ]
  4. Clinical Global Impression of change [ Time Frame: 9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both ]
  5. Patient Global Impression of change [ Time Frame: 9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both ]
  6. Change in the number of seizure-free days [ Time Frame: 9 wks (cohort 1), 14 wks (cohort 2) and 52 weeks (both ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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, subjects 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 subject 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 time 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 subject 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01963208

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Sponsors and Collaborators
Marinus Pharmaceuticals
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Study Director: Joseph Hulihan, M.D. Marinus Pharmaceuticals, Inc.
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Responsible Party: Marinus Pharmaceuticals Identifier: NCT01963208    
Other Study ID Numbers: 1042-0603
First Posted: October 16, 2013    Key Record Dates
Last Update Posted: August 26, 2020
Last Verified: August 2020
Keywords provided by Marinus Pharmaceuticals:
partial onset seizures
complex partial seizures
simple partial seizures
Additional relevant MeSH terms:
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Neurologic Manifestations
Nervous System Diseases
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
GABA Modulators
GABA Agents