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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00441896
• Date of registration: 27/02/2007
• Prospective Registration: No
• Primary sponsor: Marinus Pharmaceuticals
• Public title: A Randomized, Controlled Trial of Ganaxolone in Patients With Infantile Spasms
• Scientific 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
• Date of first enrolment: January 2007
• Target sample size: 56
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00441896
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Joseph Hulihan, MD
• Affiliation: Marinus Pharmaceuticals, Inc.

Key inclusion & exclusion 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.



Age minimum: 4 Months
Age maximum: 24 Months
Gender: All

Health Condition(s) or Problem(s) studied

Infantile Spasms

Intervention(s)

Drug: Ganaxolone

Other: Placebo

Primary Outcome(s)

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

Secondary Outcome(s)

Investigator and caregiver global assessment of seizure severity and response to treatment at Weeks 1 and 2. [Time Frame: 1 week, 2 weeks]

Spasm frequency after two weeks of treatment, as determined by 24-hour vEEG. [Time Frame: 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]

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]

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]

Cessation of hypsarrhythmia, as determined by vEEG. [Time Frame: 1 week, 2 weeks]

Responders (= 50% decrease in spasm frequency) at Weeks 1 and 2. [Time Frame: 1 week, 2 weeks]

Secondary ID(s)

1042-0500

Source(s) of Monetary Support

Please refer to primary and secondary sponsors