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

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Brief Title

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

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

Brief Summary

      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.
    

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 Spasm frequency after two weeks of treatment, as determined by 24-hour vEEG.

Condition

Infantile Spasms

Intervention

Ganaxolone

Study Arms / Comparison Groups

 ganaxolone
Description:  ganaxolone

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

56

Start Date

January 2007

Completion Date

May 2008

Primary Completion Date

May 2008

Eligibility 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.
      

Gender

All

Ages

4 Months - 24 Months

Accepts Healthy Volunteers

No

Contacts

Joseph Hulihan, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00441896

Organization ID

1042-0500


Responsible Party

Sponsor

Study Sponsor

Marinus Pharmaceuticals


Study Sponsor

Joseph Hulihan, MD, Study Director, Marinus Pharmaceuticals, Inc.


Verification Date

November 2020