A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms

Overview

The study is a two period (8-10 days/period), incomplete cross-over in which successive cohorts of 9 subjects are randomized, in a 2:1 ratio, to 1 of 2 sequences, A and B. In each cohort, Sequence A, comprised of 6 subjects, receives ascending doses of ganaxolone during period 1 and ganaxolone (at the maximal dose attained in period 1) and ascending doses of placebo during period 2. Sequence B, comprised of 3 subjects, receives ascending doses of placebo during period 1 and receives the maximum dose of placebo and ascending doses of ganaxolone during period 2. The dosing level in each subsequent cohort will be based upon experience gained from previous cohorts.

Full Title of Study: “A Double-blind, Placebo-controlled, Dose-ranging Clinical Study to Evaluate the Safety, Tolerability, and Antiepileptic Activity of Ganaxolone in Treatment of Patients With Infantile Spasms”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: May 2008

Detailed Description

Male or female, 4 to 24 months of age (inclusive) with a diagnosis of IS with a 24 hour video EEG (vEEG) recording confirming the diagnosis and previously treated with 3 or fewer antiepileptic drugs (AEDs) are eligible for the study. The subject is able to continue treatment with concomitant AEDs (no more than 2; adrenocorticotropic hormone [ACTH], corticosteroids, felbamate, and vigabatrin are not allowed concomitantly). A ketogenic diet is permitted if it can be maintained for the duration of the study. There will be a total of three weekly 24-hr video EEGs (baseline, end of weeks 1 and 2 of treatment). Dosing titration begins the day after each video EEG during the inpatient stay. All subjects will be receiving ganaxolone the day after the second video EEG. A Data Monitoring Board (DMB) will determine whether successive cohorts of subjects can be dosed at an increased dose level; up to a maximum of 6 cohorts.

Interventions

  • Drug: Ganaxolone
  • Other: Placebo

Arms, Groups and Cohorts

  • Experimental: ganaxolone
    • ganaxolone
  • Placebo Comparator: non-active drug
    • placebo

Clinical Trial Outcome Measures

Primary Measures

  • Spasm frequency as measured by a 24-hour vEEG at Visit 5 (Day 9 ±1 day).
    • Time Frame: 1 week

Secondary Measures

  • Spasm frequency after two weeks of treatment, as determined by 24-hour vEEG.
    • Time Frame: 2 weeks
  • Cessation of hypsarrhythmia, as determined by vEEG.
    • Time Frame: 1 week, 2 weeks
  • Investigator and caregiver global assessment of seizure severity and response to treatment at Weeks 1 and 2.
    • Time Frame: 1 week, 2 weeks
  • The number of subjects spasm-free and seizure-free (for at least 24 hours) at Weeks 1 and 2.
    • Time Frame: 1 week, 2 weeks
  • Responders (≥ 50% decrease in spasm frequency) at Weeks 1 and 2.
    • Time Frame: 1 week, 2 weeks
  • Reduction of other seizure types at Weeks 1 and 2. Parents/caregivers will maintain a spasm/seizure diary for clinical study subjects.
    • Time Frame: 1 week, 2 weeks
  • Investigators and caregivers assessment of the presence and absence of spasms in each subject following treatment.
    • Time Frame: 1 week, 2 weeks
  • Developmental assessment.
    • Time Frame: 2 weeks

Participating in This Clinical Trial

Inclusion Criteria

  • Be diagnosed with IS (regardless of etiology- except for a progressive neurologic illness). Diagnostic Criteria: Seizures consisting of single or repetitive short muscular contractions leading to flexion or extension. Spasms may be characterized as tonic or myoclonic contractions, may occur singly or in clusters, and typically occur bilaterally and symmetrically. The EEG pattern must be consistent with the diagnosis of IS (hypsarrhythmia, modified hypsarrhythmia, multifocal spike wave discharges, etc). – Have a vEEG recording confirming the diagnosis of IS. – Have had a magnetic resonance imaging (MRI) performed to determine any possible causes of IS. – Have been previously treated with 3 or fewer AEDs. – If being treated with concomitant AEDs – Current AEDs have been at a constant daily dose for at least 2 weeks; Note: Subjects with minor dose adjustments may be allowed to enter the study after shorter periods after detailed discussion with the medical monitor. – Have a stable clinical response/plateau for at least 2 weeks – Are able to continue treatment with no more than 2 concomitant AEDs (ACTH, corticosteroids, felbamate, and vigabatrin are not allowed concomitantly). – A ketogenic diet is permitted if it can be maintained for the duration of the study. – Be a male or female, 4 to 24 months of age (inclusive) – Have a Parent/Guardian who is properly informed of the nature and risks of the clinical study, who is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study – Be able to participate for the full term of the clinical study. Exclusion Criteria:
  • Treatment with corticosteroids, ACTH, vigabatrin, felbamate, or any AED not approved by Regulatory Agencies, 2 weeks prior to randomization. – Treatment with more than two AEDs at baseline. – Have an active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive (with the exception of tuberous sclerosis) as evaluated by brain imaging (MRI). – Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk. – Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin greater than four times the upper limit of normal (ULN) or clinical laboratory value deemed clinically significant by the Investigator. – History of recurrent status epilepticus. – Have been exposed to any other investigational drug within 30 days prior to randomization.
  • Gender Eligibility: All

    Minimum Age: 4 Months

    Maximum Age: 24 Months

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Marinus Pharmaceuticals
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • Joseph Hulihan, MD, Study Director, Marinus Pharmaceuticals, Inc.

    Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

    At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.