Clinical trial NCT00418847: Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis
Official title: Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis: Single and Multiple Oral Doses
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gangliosidoses GM2
Keywords: pediatrics
lysosomal storage diseases
Gangliosidoses GM2
Tay-Sachs disease
Sandhoff disease
Infantile GM2-activator deficiency
Miglustat
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Actelion
First posted: 2007-01-05
Enrollment: 5
Sex: ALL
Minimum age (years): 6
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Concentration of miglustat in plasma
timeFrame: Periodic intervals up to 24 hours
Secondary outcomes:
measure: Changes in volume loss and signal intensity from baseline MRI
timeFrame: 12 months
measure: Change in single-voxel N acetylaspartate (NAA) from baseline MRS
timeFrame: 1 month, 3 months, 6 months, 9 months, and 12 months
measure: Change in neuropsychological testing from baseline
timeFrame: 6 months and 12 months
measure: Change in nerve conduction
timeFrame: 6 months and 12 months
measure: Change in neurological examination from baseline
timeFrame: 1 month, 3 months, 6 months, 9 months, and 12 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children, Toronto Canada
name: Joe TR Clarke, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maegawa GH, Banwell BL, Blaser S, Sorge G, Toplak M, Ackerley C, Hawkins C, Hayes J, Clarke JT. Substrate reduction therapy in juvenile GM2 gangliosidosis. Mol Genet Metab. 2009 Sep-Oct;98(1-2):215-24. doi: 10.1016/j.ymgme.2009.06.005. Epub 2009 Jun 12.