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

This study has been completed.
Sponsor:
Information provided by:
Marinus Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00441896
First received: February 27, 2007
Last updated: October 29, 2009
Last verified: October 2009
  Purpose

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.


Condition Intervention Phase
Infantile Spasms
Drug: Ganaxolone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Marinus Pharmaceuticals:

Primary Outcome Measures:
  • Spasm frequency as measured by a 24-hour vEEG at Visit 5 (Day 9 ±1 day). [ Time Frame: 1 week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Spasm frequency after two weeks of treatment, as determined by 24-hour vEEG. [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Cessation of hypsarrhythmia, as determined by vEEG. [ Time Frame: 1 week, 2 weeks ] [ Designated as safety issue: No ]
  • Investigator and caregiver global assessment of seizure severity and response to treatment at Weeks 1 and 2. [ Time Frame: 1 week, 2 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Responders (≥ 50% decrease in spasm frequency) at Weeks 1 and 2. [ Time Frame: 1 week, 2 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Investigators and caregivers assessment of the presence and absence of spasms in each subject following treatment. [ Time Frame: 1 week, 2 weeks ] [ Designated as safety issue: No ]
  • Developmental assessment. [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: January 2007
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ganaxolone Drug: Ganaxolone
Placebo Comparator: non-active drug Drug: Ganaxolone

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.

  Eligibility

Ages Eligible for Study:   4 Months to 24 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00441896

Locations
United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
Mattel Children's Hospital at UCLA
Los Angeles, California, United States, 90095
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Miami Children's Hospital, The Brain Institute
Miami, Florida, United States, 33155
Child Neurology Care Center of Northwest Florida
Pensacola, Florida, United States, 32504
Child Neurology Center of Northwest Florida
Pensacola, Florida, United States
United States, Illinois
University of Chicago Comer Children's Hospital
Chicago, Illinois, United States, 60637
United States, Minnesota
Minnesota Epilepsy Group, P.A.
St. Paul, Minnesota, United States, 55102
United States, New York
Montefiore Medical Center- Albert Einstein College of Medicine
Bronx, New York, United States, 10467
United States, Tennessee
Le Bonheur Children's Medical Center
Memphis, Tennessee, United States, 38105
United States, Texas
Dallas Pediatric Neurology Associates
Dallas, Texas, United States, 75230
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University Health System
Richmond, Virginia, United States, 23298
United States, Washington
Children's Hospital and Regional Medical Center
Seattle, Washington, United States, 98105
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53201
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: NCT00441896     History of Changes
Other Study ID Numbers: 1042-0500
Study First Received: February 27, 2007
Last Updated: October 29, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Marinus Pharmaceuticals:
infantile spasms
anticonvulsant
pediatric epilepsy
West Syndrome
epileptic spasms

Additional relevant MeSH terms:
Spasm
Spasms, Infantile
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases

ClinicalTrials.gov processed this record on July 20, 2014