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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2008 by The Hospital for Sick Children.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Actelion
Information provided by:
The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00418847
First received: January 4, 2007
Last updated: March 11, 2010
Last verified: January 2008
History of Changes
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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:

Drug Information available for: Miglustat
U.S. FDA Resources

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in volume loss and signal intensity from baseline MRI [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Change in single-voxel N acetylaspartate (NAA) from baseline MRS [ Time Frame: 1 month, 3 months, 6 months, 9 months, and 12 months ] [ Designated as safety issue: No ]
  • Change in neuropsychological testing from baseline [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]
  • Change in nerve conduction [ Time Frame: 6 months and 12 months ] [ Designated as safety issue: No ]
  • Change in neurological examination from baseline [ Time Frame: 1 month, 3 months, 6 months, 9 months, and 12 months ] [ Designated as safety issue: No ]

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

  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

No publications provided

Responsible Party: Joe Clarke/Principal Investigator, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00418847     History of Changes
Other Study ID Numbers: 1000004763
Study First Received: January 4, 2007
Last Updated: March 11, 2010
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

Additional relevant MeSH terms:
Gangliosidoses
Tay-Sachs Disease
Gangliosidoses, GM2
Sphingolipidoses
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
Lipidoses
 Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Miglustat
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013