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Completed

NCT Number: NCT00418847

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

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.

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Key information

Conditions

Gangliosidoses GM2 Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Gangliosidoses Gangliosidoses, GM2 Genetic Diseases, Inborn Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Sandhoff Disease Sphingolipidoses Tay-Sachs Disease

Age range

6 year–20 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

miglustat

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.

Other names: Zavesca

Primary outcomes

  1. Concentration of miglustat in plasma

    Time frame: Periodic intervals up to 24 hours

Secondary outcomes

  1. Changes in volume loss and signal intensity from baseline MRI

    Time frame: 12 months

  2. Change in single-voxel N acetylaspartate (NAA) from baseline MRS

    Time frame: 1 month, 3 months, 6 months, 9 months, and 12 months

  3. Change in neuropsychological testing from baseline

    Time frame: 6 months and 12 months

  4. Change in nerve conduction

    Time frame: 6 months and 12 months

  5. Change in neurological examination from baseline

    Time frame: 1 month, 3 months, 6 months, 9 months, and 12 months

Sponsors and collaborators

Lead sponsor

The Hospital for Sick Children

Other

Collaborators

  • Actelion

Registry information

Official study title

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

Important dates

Study start
2004
Primary completion
2009
Study completion
2009
First posted
Jan 5, 2007
Registry last updated
May 19, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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