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

NCT ID: NCT00418847

Last Updated: 2016-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2009-04-30

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.

Conditions

Gangliosidoses GM2

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

miglustat

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Zavesca

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joe TR Clarke, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children, Toronto Canada

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 19595619 (View on PubMed)

Other Identifiers

1000004763

Identifier Type: -

Identifier Source: org_study_id