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

Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset GM2 Gangliosidosis: Single and Steady State Oral Doses

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.

Study Overview

• Status: Completed
• Conditions: Sandhoff Disease; GM2 Gangliosidoses; Tay-Sachs
• Intervention / Treatment: Drug: Zavesca (Miglustat)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. 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.
2. Onset of characteristic clinical symptoms of the disease before the age of 9 months.
3. Normal renal and hepatic function.
4. Written informed consent from parent or legal guardian.

Exclusion criteria

1. 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.
2. Patients receiving other investigational agents within 3 months of study initiation.
3. Patients who are anemic (hemoglobin < 11 g/dl, and/or hematocrit < 34%)
4. 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.
5. Patients with a high probability of dying during the 6-month assessment period of the study.
6. Patients who in the opinion of the investigator (for whatever reason) are thought to be unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
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.

Collaborators and Investigators

• Sponsor: Children's National Research Institute
• Collaborators: Actelion
• Investigators: Principal Investigator: Cynthia J TIfft, MD, PhD, Children's National Research Institute

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: May 2, 2008
• First Submitted That Met QC Criteria: May 5, 2008
• First Posted (Estimate): May 6, 2008

Study Record Updates

• Last Update Posted (Estimate): May 6, 2008
• Last Update Submitted That Met QC Criteria: May 5, 2008
• Last Verified: July 1, 2005

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gangliosidoses; Gangliosidoses, GM2; Tay-Sachs Disease; Sandhoff Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Glycoside Hydrolase Inhibitors; Miglustat
• Other Study ID Numbers: 3445