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A 24-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00283933
Recruitment Status : Completed
First Posted : January 31, 2006
Results First Posted : September 7, 2018
Last Update Posted : September 7, 2018
Information provided by (Responsible Party):
Amicus Therapeutics

Brief Summary:
Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.

Condition or disease Intervention/treatment Phase
Fabry Disease Drug: migalastat HCl Phase 2

Detailed Description:
This was a Phase 2, open-label study in male participants with Fabry disease. The study consisted of a 4-week screening period, during which participants' galactosidase (GLA) genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat. Participants were required to have α-Gal A activity responsive to migalastat. The study consisted of a 24-week treatment period, followed by an optional 24-week extension period. Participants received migalastat once every other day (QOD) for 24 weeks during the treatment period and the optional 24-week extension for a total treatment duration of up to 48 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Single Dose Level, 24-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Patients With Fabry Disease
Actual Study Start Date : May 9, 2006
Actual Primary Completion Date : March 12, 2008
Actual Study Completion Date : March 12, 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Migalastat
Migalastat 150 milligrams (mg) was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period.
Drug: migalastat HCl
Other Names:
  • AT1001
  • Galafold
  • migalastat

Primary Outcome Measures :
  1. Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (after dosing) through Week 48 ]
    TEAEs were defined as any adverse event with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Secondary Outcome Measures :
  1. α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48 [ Time Frame: Baseline, Week 24 (end of treatment period), Week 48 (end of extension period) ]
    PBMC were isolated from whole blood and lysed, and α-Gal A activity was measured using a validated fluorometric assay, with catalysis to fluorescent 4-methylumbelliferone (4-MU) as the activity measure. The activity values obtained were normalized to protein (measured using a colorimetric assay) and reported as enzyme activity (nanomole [nmol] 4-MU/hour [hr]) per mg of protein. On Day 1 of the first visit and at every visit thereafter, the samples were collected prior to dosing with migalastat. α-Gal A activity in leukocytes are presented by individual participants.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males between 18 and 65 years of age (inclusive)
  • Hemizygous for Fabry disease
  • Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
  • Had enhanceable enzyme activity based on in vitro tests
  • Had documented evidence of cardiac and/or renal dysfunction (for example, abnormal electrocardiogram (ECG), left ventricular hypertrophy, renal insufficiency)
  • Were previously untreated by enzyme replacement therapy (ERT) or substrate depletion for Fabry disease, or if ERT or other specific treatment for Fabry disease was administered, were able to stop ERT for at least 30 weeks.
  • Were willing to undergo 2 kidney and 3 skin biopsies
  • Agreed to be sexually abstinent or use a condom with spermicide when engaging in sexual activity during the course of the study and for a period of 30 days following completion of the study
  • Were willing and able to sign an informed consent form

Exclusion Criteria:

  • History of significant disease other than Fabry disease (for example, end-stage renal disease; Class III or IV heart disease [per the New York Heart Association classification]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes [unless hemoglobin A1c ≤8]; or neurological disease that would have impaired the participant's ability to participate in the study)
  • History of organ transplant
  • Serum creatinine >176 millimole per deciliter on Day -2
  • Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds prior to dosing
  • Taking a medication prohibited by the protocol: Fabrazyme® (agalsidase beta), Replagal™ (agalsidase alfa), Glyset® (miglitol), Zavesca® (miglustat), or any experimental therapy for any indication
  • Participated in a previous clinical trial in the last 30 days
  • Any other condition, which, in the opinion of the investigator, would jeopardize the safety of the participant or impact the validity of the study results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00283933

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Paris, France, 75015
United Kingdom
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Amicus Therapeutics
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Study Director: Medical Monitor, Clinical Research Amicus Therapeutics

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Amicus Therapeutics Identifier: NCT00283933    
Other Study ID Numbers: FAB-CL-203 (AA1565522)
First Posted: January 31, 2006    Key Record Dates
Results First Posted: September 7, 2018
Last Update Posted: September 7, 2018
Last Verified: August 2018
Keywords provided by Amicus Therapeutics:
Amicus Therapeutics
Additional relevant MeSH terms:
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Fabry Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action