Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis - Full Text View

Purpose

The purpose of the study is to investigate the pharmacokinetics of Zavesca (miglustat, OGT918) when given as single and multiple doses in juvenile patients with GM2 gangliosidosis.

Condition	Intervention	Phase
Gangliosidoses GM2	Drug: miglustat	Phase II

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

ChemIDplus related topics:

SC 48334

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study

Official Title:	Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis: Single and Multiple Oral Doses

Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:

concentration of miglustat in plasma at periodic intervals up to 24 hours

Secondary Outcome Measures:

changes in volume loss and signal intensity from baseline MRI to 12 months
change in single-voxel N acetylaspartate (NAA) from baseline MRS to 12 months
change in neuropsychological testing
change in nerve conduction at 12 months
change in neurological examination at 12 months

Estimated Enrollment:	5
Study Start Date:	July 2004
Estimated Study Completion Date:	October 2006

Detailed Description:

The GM2 gangliosidoses are a group of neuro-degenerative lysosomal storage diseases resulting from accumulation of GM2 and related glycolipids in the central nervous system (CNS). Tay-Sachs and Sandhoff disease are two variants which are indistinguishable in clinical grounds. According to the onset and rate of disease progression, the condition can be categorized in infantile, juvenile and adult forms. This open-label, single-arm study is designed to assess the pharmacokinetics, safety and tolerability of miglustat in juvenile patients. Miglustat will be administered at a maximum dose of 600 mg/day, divided into three doses per day. The dose used for patients in this pediatric age range will be related to the patient’s body surface area. The pharmacokinetics assessments for the study will be performed in-hospital during a 24 hour period, and will take place at the day one and at the month 3 visits. The clinical (which includes safety and tolerability) assessments will be performed throughout the 24-month study period.

Eligibility

Ages Eligible for Study:	6 Years to 20 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of GM2 gangliosidosis confirmed by demonstration of profound deficiency of β-hexosaminidase A or A & B in peripheral blood leukocytes or cultured skin fibroblasts
Aged 6 to 20 years
Onset of characteristic clinical symptoms of the disease before age 15 years
Normal renal or hepatic function

Exclusion Criteria:

Fertile patients who do not agree to use adequate contraception throughout the study and for 3 months after cessation of miglustat treatment.
Patients who cannot tolerate the study procedures, cannot be compliant to therapy or who are unable to travel to the study center as required by this protocol.
Patients receiving other investigational agents within 3 months of study initiation.
Patients with disease that may affect absorption or elimination of drugs.
Patients suffering from clinically significant diarrhea (>3 liquid stools per day for > 7 days) without definable cause within 3 months of baseline visit, or who have a history of significant gastrointestinal disorders.
Patients with swallowing difficulties.
Patients with a high probability of dying during 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: NCT00418847

Locations


Canada, Ontario
	The Hospital for Sick Children
	Toronto, Ontario, Canada, M5G 1X8

Sponsors and Collaborators

The Hospital for Sick Children

Actelion

Investigators


Principal Investigator:	Joe TR Clarke, MD	The Hospital for Sick Children, Toronto Canada

More Information

Study ID Numbers:	1000004763
First Received:	January 4, 2007
Last Updated:	January 4, 2007
ClinicalTrials.gov Identifier:	NCT00418847
Health Authority:	Canada: Health Canada

Keywords provided by The Hospital for Sick Children:

pediatrics

lysosomal storage diseases

Gangliosidoses GM2

Tay-Sachs disease

Sandhoff disease

Infantile GM2-activator deficiency

Miglustat

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 September 05, 2008

Sponsors and Collaborators:	The Hospital for Sick Children Actelion
Information provided by:	The Hospital for Sick Children
ClinicalTrials.gov Identifier:	NCT00418847