Oral Miglustat in Adult Patients With Stable Type 1 Gaucher Disease - Full Text View

Purpose

Although miglustat has been approved as a treatment for mild to moderate type 1 Gaucher disease in patients who are unsuitable for enzyme replacement therapy (ERT), more data are required to establish the long term efficacy, safety and tolerability of miglustat in maintaining diseases stability after a switch from ERT.

Condition	Intervention	Phase
Type 1 Gaucher Disease	Drug: miglustat	Phase 3


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Open-label, Non Comparative, Multi-center Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Oral Miglustat as a Maintenance Therapy After a Switch From Enzyme Replacement Therapy in Adult Patients With Stable Type 1 Gaucher Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Gaucher disease Schindler disease succinic semialdehyde dehydrogenase deficiency

MedlinePlus related topics: Gaucher's Disease

Drug Information available for: Miglustat

Genetic and Rare Diseases Information Center resources: Gaucher Disease Gaucher Disease Type 1 Sphingolipidosis

U.S. FDA Resources

Further study details as provided by Actelion:

Primary Outcome Measures:

Liver Volume [ Time Frame: baseline to end of treatment (month 24 or imputed value) ] [ Designated as safety issue: No ]
Liver volume was assessed at baseline and end of treatment by magnetic resonance imaging
Percent Change in Liver Volume [ Time Frame: baseline to end of treatment (month 24 or imputed value) ] [ Designated as safety issue: No ]
Liver volume was assessed at baseline and end of treatment by magnetic resonance imaging

Secondary Outcome Measures:

Spleen Volume [ Time Frame: baseline to end of treatment (month 24 or imputed value) ] [ Designated as safety issue: No ]
Spleen volume was assessed at baseline and end of treatment by magnetic resonance imaging
Percent Change in Spleen Volume [ Time Frame: baseline to end of treatment (month 24 or imputed value) ] [ Designated as safety issue: No ]
Spleen volume was assessed at baseline and end of treatment by magnetic resonance imaging


Enrollment:	42
Study Start Date:	February 2006
Study Completion Date:	July 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: miglustat miglustat oral capsules 100mg three times daily (TID) Other Name: Zavesca

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males or females aged 18 years or older
Type 1 Gaucher disease, diagnosed by glucocerebrosidase assay or molecular analysis of the glucocerebrosidase gene.
Treatment with ERT for at least 3 years, with a stable dose regimen for at least the last 6 months.
Clinically and biologically stable disease for the previous 2 years, with at least 2 time points assessments (including Baseline as one potential time point), defined as:
- Stable organomegaly (assessed by magnetic resonance imaging (MRI) or computed tomography (CT)):
  - Liver volume within 10% of the mean.
  - Spleen volume within 10% of the mean.
- Free of progressive symptomatic documented bone disease.
- Hemoglobin levels > 11g/dl
- Mean platelet count > 100x109 /l.
- Chitotriosidase activity within 20% of the mean. - If chitotriosidase is not available (in the case of chitotriosidase deficiency, or if it was not determined), other relevant biomarkers (e.g., angiotensin converting enzyme (ACE), tartrate resistant acid phosphatase (TRAP) and ferritin) could be considered.
Written informed consent.

Exclusion Criteria:

History or evidence of oculomotor gaze palsy, ataxia or other clinical manifestations typically associated with neuronopathic type 3 Gaucher disease.
Not ambulant patients, or with progressive symptomatic documented bone disease.
Splenectomy before 18 years of age for splenomegaly and/or thrombocytopenia.
Peripheral polyneuropathy (not mononeuropathy) documented with both clinical signs and symptoms, and electrodiagnostic (EDX).
Patients (males and females) who do not agree to use reliable contraception throughout the study and for 3 months after cessation of miglustat treatment.
Female patients who are pregnant or breast feeding, or without pregnancy test prior to Day 1.
History of significant lactose intolerance.
Clinically significant diarrhea (>3 liquid stools per day for >7 days) without definable cause within 6 months prior to Day 1, or a history of clinically relevant gastrointestinal disorders.
History of cataracts or known increased risk of cataract formation.
Severe renal impairment i.e., with a creatinine clearance <30 ml/min/1.73m^2
Concomitant active medical condition such as human immunodeficiency virus (HIV) or hepatitis B/C that would render patients unsuitable for study.
Previous treatment with miglustat.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319046

Show 20 Study Locations

Sponsors and Collaborators

Actelion

Investigators


Principal Investigator:	Timothy Cox, Prof	University of Cambridge

More Information

No publications provided by Actelion

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cox TM, Amato D, Hollak CE, Luzy C, Silkey M, Giorgino R, Steiner RD; Miglustat Maintenance Study Group. Evaluation of miglustat as maintenance therapy after enzyme therapy in adults with stable type 1 Gaucher disease: a prospective, open-label non-inferiority study. Orphanet J Rare Dis. 2012 Dec 27;7:102. doi: 10.1186/1750-1172-7-102.


Responsible Party:	Actelion
ClinicalTrials.gov Identifier:	NCT00319046 History of Changes
Other Study ID Numbers:	OGT 918-011
Study First Received:	April 26, 2006
Results First Received:	April 24, 2012
Last Updated:	May 24, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Actelion:


Type 1 Gaucher Disease miglustat enzyme replacement therapy

Additional relevant MeSH terms:


Gaucher Disease Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases 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 Sphingolipidoses Miglustat Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015