Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses - Full Text View

Sponsors and Collaborators:	Children's Research Institute Actelion
Information provided by:	Children's Research Institute
ClinicalTrials.gov Identifier:	NCT00672022

Purpose

We want to see if Zavesca (or miglustat) is safe and can be tolerated by patients with acute infantile onset GM2 gangliosidosis - classical Tay-Sachs and infantile onset Sandhoff disease. We know that miglustat inhibits the formation of GM2 ganglioside, the compound that is stored in the brains of children with Tay-Sachs and Sandhoff disease. Since it inhibits the synthesis of ganglioside, miglustat may be able to reduce or delay the onset of clinical symptoms.

Condition	Intervention	Phase
GM2 Gangliosidoses Tay-Sachs Sandhoff Disease	Drug: Zavesca (Miglustat)	Phase III

Genetics Home Reference related topics: cholesteryl ester storage disease Farber lipogranulomatosis GM2-gangliosidosis, AB variant long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency mitochondrial trifunctional protein deficiency primary carnitine deficiency Sandhoff disease Tay-Sachs disease

MedlinePlus related topics: Tay-Sachs Disease

Drug Information available for: SC 48334

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset GM2 Gangliosidosis: Single and Steady State Oral Doses

Further study details as provided by Children's Research Institute:

Primary Outcome Measures:

Biomarkers (level of GM2 ganglioside, chitotriosidase activity, anti-GM2 antibodies) in plasma, serum and CSF will be measured at initial visit (run-in period), Week 13, and Week 25.

Secondary Outcome Measures:

Neurophysiologic Assessment - EEG and BEAR tests will be done at initial visit (run-in period), Week 13, and Week 25.
Ophthalmology Assessment - comparision of the "cherry-red" macula changes will be made at initial visit (run-in period) and Week 25.

Estimated Enrollment:	10
Study Start Date:	July 2004
Study Completion Date:	August 2007
Primary Completion Date:	August 2007 (Final data collection date for primary outcome measure)

Detailed Description:

Specific Aims

The primary objective of the study is to investigate the pharmacokinetics of ZAVESCA® (miglustat, OGT918), when given as a single dose and at steady state, in infantile patients with GM2 gangliosidosis. The secondary objectives are to evaluate the tolerability and safety of single and multiple doses of miglustat and to monitor disease progression using physical and developmental assessments and disease-specific biomarkers.

Eligibility

Ages Eligible for Study:	6 Months to 5 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria

Diagnosis of GM2 gangliosidosis, confirmed by demonstration of profound deficiency of -hexosaminidase A or A & B in peripheral blood leukocytes or in cultured skin fibroblasts, within the previous 1 year in non-bone marrow transplant recipients who are < 2 years of age, or prior to stem cell transplant in stably engrafted transplant patients who are < 5 years of age.
Onset of characteristic clinical symptoms of the disease before the age of 9 months.
Normal renal and hepatic function.
Written informed consent from parent or legal guardian.

Exclusion criteria

Patients who are unable to comply with the study procedures of this protocol, including the refusal to swallow the food used to mask the taste of the study drug and whose parents are unwilling to administer the drug through a nasogastric or gastrostomy tube.
Patients receiving other investigational agents within 3 months of study initiation.
Patients who are anemic (hemoglobin < 11 g/dl, and/or hematocrit < 34%)
Patients who have a history of significant gastrointestinal disorders, including clinically significant diarrhea (>3 liquid stools per day for > 7 days), without definable cause within 3 months of baseline visit.
Patients with a high probability of dying during the 6-month assessment period of the study.
Patients who in the opinion of the investigator (for whatever reason) are thought to be unsuitable for the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00672022

Locations

United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010

Sponsors and Collaborators

Children's Research Institute

Actelion

Investigators

Principal Investigator:

Cynthia J TIfft, MD, PhD

Childrens Research Institute

More Information

Study ID Numbers:	3445
Study First Received:	May 2, 2008
Last Updated:	May 5, 2008
ClinicalTrials.gov Identifier:	NCT00672022
Health Authority:	United States: Institutional Review Board

Study placed in the following topic categories:

Lipid Metabolism, Inborn Errors
Gangliosidosis (GM2) Type1
Sphingolipidoses
Metabolic Diseases
Lysosomal Storage Diseases
Sphingolipidosis
Central Nervous System Diseases
Tay-Sachs disease
Brain Diseases
Metabolism, Inborn Errors
Miglustat

Genetic Diseases, Inborn
Gangliosidoses, GM2
Brain Diseases, Metabolic, Inborn
Lipidoses
Metabolic disorder
Tay-Sachs Disease
Sandhoff disease
Gangliosidoses
Sandhoff Disease
Lipid Metabolism Disorders
Brain Diseases, Metabolic

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents
Molecular Mechanisms of Pharmacological Action
Lysosomal Storage Diseases, Nervous System

Therapeutic Uses
Nervous System Diseases
Enzyme Inhibitors
Antiviral Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009