Open-label Extension to Protocol 1042-0500

Infantile Spasms Clinical Trial

Official title:

An Open-label Clinical Study to Evaluate the Safety and Antiepileptic Activity of Ganaxolone in Treatment of Patients Diagnosed With Infantile Spasms.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00442104
• Other study ID #: 1042-0501
• Secondary ID: Amend 5 (ROW)Ame
• Status: Terminated
• Phase: Phase 2
• Start date: January 2007
• Est. completion date: March 2009

Study information

• Verified date: May 2024
• Source: Marinus Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To allow open-label extension to patients who have completed Protocol 1042-0500

Description:

Patient should have completed all scheduled clinical study visits in the double blind, controlled trial (Protocol 1042-0500) and have been deemed eligible (had a response to treatment) by the Investigator. Male or female, with a diagnosis of IS with a video EEG (vEEG) recording confirming the diagnosis. There will be a total of 14 visits over 99(+or-1)week. A 24-hr vEEG is only required if the subject has been spasm-free for more than 24-hrs.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 54
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Months to 24 Months

Eligibility

Inclusion Criteria:

• Have completed all scheduled clinical study visits in the previous Protocol 1042 0500 and have been deemed eligible (no SAEs thought to be drug related and had a response to treatment) by the Investigator.
• Be diagnosed with IS regardless of etiology. 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 24 hour 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 AEDs or fewer.
• Have a parent/guardian who is properly informed of the nature and potential risks and benefits of the clinical study, is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study.

Exclusion Criteria:

• Current treatment with more than 2 concomitant AEDs.
• 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 MRI.
• Have any disease or condition (medical or surgical) at Screening that might compromise the hematologic, cardiovascular, pulmonary, renal, GI, 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 transaminase (AST), alanine transaminase (ALT), or total bilirubin greater than 4 times the upper limit of laboratory normal or any 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 enrollment.

Related Conditions & MeSH terms

• Infantile Spasms
• Spasm
• Spasms, Infantile

Intervention

Drug:
• Ganaxolone

Locations

Country	Name	City	State
United States	Montefiore Medical Center- Albert Einstein College of Medicine	Bronx	New York
United States	University of Chicago Comer Children's Hospital	Chicago	Illinois
United States	Dallas Pediatric Neurology Associates	Dallas	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Mattel Children's Hospital at UCLA	Los Angeles	California
United States	Le Bonheur Children's Medical Center	Memphis	Tennessee
United States	Miami Children's Hospital, The Brain Institute	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Child Neurology Center of Nrothwest Florida, P.A.	Pensacola	Florida
United States	Virginia Commonwealth University Health Systems	Richmond	Virginia
United States	Minnesota Epilepsy Group, P.A.	Saint Paul	Minnesota
United States	Children's Hospital and Regional Medical Center	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Marinus Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Were Free of Spasms	Clinical spasms were determined by video-electroencephalography (VEEG). The number of participants with spasm-free duration have been presented.	Weeks 4 through Week 96
Secondary	Change From Baseline in Frequency of Spasm Clusters	Infantile spasms that come one after another in a cluster and lasts several minutes are called Spasm Clusters. Spasm clusters were determined by a 24-hour video-electroencephalography (vEEG). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment prior to ganaxolone dosing in Protocol 1042-0500.	Baseline and Week 4 through Week 32
Secondary	Change From Baseline in Frequency of Individual Spasm	Individual Spasm are seizures that may last only a second or two and were determined by a 24-hour video-electroencephalography (vEEG). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment prior to ganaxolone dosing in Protocol 1042-0500.	Baseline and Week 4 through Week 32
Secondary	Number of Participants With Change in Clinical Status on Caregiver's Global Assessment	Caregiver global assessment of seizure severity and response to treatment rated the participants' based on 7 clinical factors: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale ([1] marked improvement, [2] moderate improvement, [3] slight improvement, [4] no change from baseline, [5] slight worsening, [6] moderate worsening, or [7] marked worsening). Higher score indicated worse symptoms. The assessment compared the participants' current status to their condition prior to initiating study medication.	Week 4 through Week 32
Secondary	Number of Participants With Change in Clinical Status on the Investigator's Global Assessment	The investigators rated the participants' overall clinical status based on 7 clinical factors: seizure frequency, duration, and intensity; adverse experiences; social, intellectual, and motor functioning. Using a 7-point scale ([1] marked improvement, [2] moderate improvement, [3] slight improvement, [4] no change from baseline, [5] slight worsening, [6] moderate worsening, or [7] marked worsening). Higher score indicated worse symptoms. The investigators assessed the participants' status compared to their condition prior to initiating study medication.	Week 4 through Week 32
Secondary	Number of Participants With Spasm-free Durations	Spasm-free duration is defined as total number of spasm-free days recorded in the spasm/seizure diary. Parents/Guardians or nursing staff maintained a spasm/seizure diary to record the number and type of seizures each day, including spasms, throughout the entire study. The number of participants with spasm-free duration of at least 24 hours have been presented.	Week 4 through Week 32
Secondary	Number of Participants With Absence of Spasms	Absence of spasms is defined as percentage of total spasm-free days during a visit period=100%. Parents/Guardians or nursing staff maintained a spasm/seizure diary to record the number and type of seizures each day, including spasms, throughout the entire study. The participants achieving absence of spasms have been presented.	Week 4 through Week 32
Secondary	Developmental Assessment Using Denver-II Developmental Test	Denver-II Developmental Test measures a child's development in several areas:Personal-Social,Fine Motor-Adaptive,Language,and Gross Motor,from birth to 6 years old.It consists of 125 items that are organized into subscales and scored as pass,fail,or refused.To evaluate a child's progress,test compares their performance to a normative sample of children of same age.For each item,age at which 90% of children in normative sample pass it is determined.Derived score for each subscale is sum of item scores and represents difference between child's chronological age and age at which 90% of children in normative sample pass the items in that subscale.A higher derived score on a subscale indicates better performance on items in that subscale relative to other children of same age who have taken the test.Among subscales,Personal-Social subscale ranges from -16 months to 24 months;others range from - 12 months to 24 months.All subscales have a population mean of 0 and a standard deviation of 3.	Week 8 through Week 32
Secondary	Percentage of Total Spasm-free Days and Cumulative Spasm-free Days as Determined From the Seizure Diary.	Percentage of total spasm-free days during a visit period is defined as total number of spasm free days as recorded in the Seizure Diary/ total number of days during that period, multiplied by 100.; Percentage of cumulative total spasm-free days during a visit period is defined as sum of total number of spasm-free days during this period as recorded in the Seizure Diary/ total number of days in the treatment period, multiplied by 100.	Weeks 4 through Week 32