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Trial record 5 of 20 for:    Tay-Sachs Disease

Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis

This study has been completed.
Information provided by (Responsible Party):
The Hospital for Sick Children Identifier:
First received: January 4, 2007
Last updated: May 18, 2016
Last verified: May 2016
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 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis: Single and Multiple Oral Doses

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Concentration of miglustat in plasma [ Time Frame: Periodic intervals up to 24 hours ]

Secondary Outcome Measures:
  • Changes in volume loss and signal intensity from baseline MRI [ Time Frame: 12 months ]
  • Change in single-voxel N acetylaspartate (NAA) from baseline MRS [ Time Frame: 1 month, 3 months, 6 months, 9 months, and 12 months ]
  • Change in neuropsychological testing from baseline [ Time Frame: 6 months and 12 months ]
  • Change in nerve conduction [ Time Frame: 6 months and 12 months ]
  • Change in neurological examination from baseline [ Time Frame: 1 month, 3 months, 6 months, 9 months, and 12 months ]

Enrollment: 5
Study Start Date: July 2004
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: miglustat
Target dose of 320 mg/m^2/day (divided in 3 doses) will be based on the Body Surface Area (BSA). For children with a BSA > 1.3, 200 mg TID will be administered. For children with a BSA of 0.8-1.3, 100 mg TID will be administered.
Other Name: Zavesca

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.

Ages Eligible for Study:   6 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
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Please refer to this study by its identifier: NCT00418847

Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
The Hospital for Sick Children
Principal Investigator: Joe TR Clarke, MD The Hospital for Sick Children, Toronto Canada
  More Information

Responsible Party: The Hospital for Sick Children Identifier: NCT00418847     History of Changes
Other Study ID Numbers: 1000004763
Study First Received: January 4, 2007
Last Updated: May 18, 2016

Keywords provided by The Hospital for Sick Children:
lysosomal storage diseases
Gangliosidoses GM2
Tay-Sachs disease
Sandhoff disease
Infantile GM2-activator deficiency

Additional relevant MeSH terms:
Tay-Sachs Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Gangliosidoses, GM2
Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs processed this record on September 21, 2017