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

Gangliosidoses GM2 Clinical Trial

Official title:

Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis: Single and Multiple Oral Doses

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00418847
• Other study ID #: 1000004763
• Status: Completed
• Phase: Phase 2
• First received: January 4, 2007
• Last updated: May 18, 2016
• Start date: July 2004
• Est. completion date: April 2009

Study information

• Verified date: May 2016
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 20 Years

Eligibility

Inclusion Criteria:

• Diagnosis of GM2 gangliosidosis confirmed by demonstration of profound deficiency of ß-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.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gangliosidoses
• Gangliosidoses GM2
• Gangliosidoses, GM2
• Tay-Sachs Disease

Intervention

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.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
The Hospital for Sick Children	Actelion

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of miglustat in plasma		Periodic intervals up to 24 hours	No
Secondary	Changes in volume loss and signal intensity from baseline MRI		12 months	No
Secondary	Change in single-voxel N acetylaspartate (NAA) from baseline MRS		1 month, 3 months, 6 months, 9 months, and 12 months	No
Secondary	Change in neuropsychological testing from baseline		6 months and 12 months	No
Secondary	Change in nerve conduction		6 months and 12 months	No
Secondary	Change in neurological examination from baseline		1 month, 3 months, 6 months, 9 months, and 12 months	No