A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
Condition: Infantile Spasms
MeSH terms: Muscle Cramp; Spasm; Spasms, Infantile
Intervention: Ganaxolone; Placebo
Intervention MeSH terms: Ganaxolone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 57.0
Sex: All
Minimum age: 4 Months
Maximum age: 24 Months
Healthy volunteers: No
Keywords: infantile spasms; anticonvulsant; pediatric epilepsy; West Syndrome; epileptic spasms

Summary:

      The study consists of cohorts where participants are randomized, in a 2:1 ratio, to 1 of 2
      sequences, A and B. In each cohort, Sequence A, comprised of participants, who will receive
      ascending doses of ganaxolone and ascending doses of placebo. Sequence B, comprised of
      participants, who will receive ascending doses of placebo and ascending doses of ganaxolone.
      The dosing level in each subsequent cohort will be based upon experience gained from previous
      cohorts.
    

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.