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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00418847
Recruitment Status : Completed
First Posted : January 5, 2007
Last Update Posted : May 19, 2016
Information provided by (Responsible Party):
The Hospital for Sick Children

Brief Summary:
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 or disease Intervention/treatment Phase
Gangliosidoses GM2 Drug: miglustat Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
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
Study Start Date : July 2004
Actual Primary Completion Date : April 2009
Actual Study Completion Date : April 2009

Arm Intervention/treatment
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

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

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

Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00418847

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Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
The Hospital for Sick Children
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Principal Investigator: Joe TR Clarke, MD The Hospital for Sick Children, Toronto Canada
Publications of Results:
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Responsible Party: The Hospital for Sick Children Identifier: NCT00418847    
Other Study ID Numbers: 1000004763
First Posted: January 5, 2007    Key Record Dates
Last Update Posted: May 19, 2016
Last Verified: May 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:
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Gangliosidoses, GM2
Tay-Sachs Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
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