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

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ClinicalTrials.gov Identifier: NCT00418847
Recruitment Status : Completed
First Posted : January 5, 2007
Last Update Posted : May 19, 2016
Sponsor:
Collaborator:
Actelion
Information provided by (Responsible Party):
The Hospital for Sick Children

Tracking Information
First Submitted Date  ICMJE January 4, 2007
First Posted Date  ICMJE January 5, 2007
Last Update Posted Date May 19, 2016
Study Start Date  ICMJE July 2004
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2010)
Concentration of miglustat in plasma [ Time Frame: Periodic intervals up to 24 hours ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 4, 2007)
concentration of miglustat in plasma at periodic intervals up to 24 hours
Change History Complete list of historical versions of study NCT00418847 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2010)
  • Changes in volume loss and signal intensity from baseline MRI [ Time Frame: 12 months ]
  • Change in single-voxel N acetylaspartate (NAA) from baseline MRS [ Time Frame: 1 month, 3 months, 6 months, 9 months, and 12 months ]
  • Change in neuropsychological testing from baseline [ Time Frame: 6 months and 12 months ]
  • Change in nerve conduction [ Time Frame: 6 months and 12 months ]
  • Change in neurological examination from baseline [ Time Frame: 1 month, 3 months, 6 months, 9 months, and 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2007)
  • changes in volume loss and signal intensity from baseline MRI to 12 months
  • change in single-voxel N acetylaspartate (NAA) from baseline MRS to 12 months
  • change in neuropsychological testing
  • change in nerve conduction at 12 months
  • change in neurological examination at 12 months
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis
Official Title  ICMJE Pharmacokinetics and Tolerability of Zavesca® (Miglustat) In Patients With Juvenile GM2 Gangliosidosis: Single and Multiple Oral Doses
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.
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gangliosidoses GM2
Intervention  ICMJE 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.
Other Name: Zavesca
Study Arms Experimental: 1
Intervention: Drug: miglustat
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 4, 2007)
5
Original Enrollment  ICMJE Same as current
Actual Study Completion Date April 2009
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages 6 Years to 20 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00418847
Other Study ID Numbers  ICMJE 1000004763
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party The Hospital for Sick Children
Study Sponsor  ICMJE The Hospital for Sick Children
Collaborators  ICMJE Actelion
Investigators  ICMJE
Principal Investigator: Joe TR Clarke, MD The Hospital for Sick Children, Toronto Canada
PRS Account The Hospital for Sick Children
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP