Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses
Information source: Children's Research Institute
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: GM2 Gangliosidoses; Tay-Sachs; Sandhoff Disease
Intervention: Zavesca (Miglustat) (Drug)
Phase: Phase 3
Sponsored by: Children's Research Institute
Official(s) and/or principal investigator(s):
Cynthia J TIfft, MD, PhD, Principal Investigator, Affiliation: Childrens Research Institute
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
Official title: Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset GM2 Gangliosidosis: Single and Steady State Oral Doses
Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Primary outcome: 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.
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.
The primary objective of the study is to investigate the pharmacokinetics of ZAVESCAŽ
(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.
Minimum age: 6 Months.
Maximum age: 5 Years.
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.
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
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
6. Patients who in the opinion of the investigator (for whatever reason) are thought to
be unsuitable for the study.
Locations and Contacts
Children's National Medical Center, Washington, District of Columbia 20010, United States
Starting date: July 2004
Ending date: August 2007
Last updated: May 5, 2008