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A Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy

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ClinicalTrials.gov Identifier: NCT00433147
Recruitment Status : Completed
First Posted : February 9, 2007
Results First Posted : August 15, 2018
Last Update Posted : August 15, 2018
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Brief Summary:
This study was conducted to test the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease already receiving enzyme replacement therapy.

Condition or disease Intervention/treatment Phase
Gaucher Disease, Type 1 Type 1 Gaucher Disease Gaucher Disease Drug: Afegostat tartrate Phase 2

Detailed Description:
This was a Phase 2, open-label study in participants with Gaucher disease, a lysosomal storage disorder. Afegostat tartrate (also known as AT2101 or isofagomine tartrate) is designed to act as a pharmacological chaperone by selectively binding to misfolded β-glucocerebrosidase (GCase) and helping it fold correctly, intended to restore GCase activity. The study consisted of a 14-day screening period, a 28-day treatment period, and a 7-day wash-out period. Participants received 1 of 4 dosing regimens for afegostat tartrate.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label Study to Assess the Safety and Tolerability of Multiple Dose Levels and Multiple Dosing Regimens of AT2101 in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy
Actual Study Start Date : March 23, 2007
Actual Primary Completion Date : February 19, 2008
Actual Study Completion Date : February 19, 2008


Arm Intervention/treatment
Experimental: Afegostat tartrate 25 milligrams (mg) once per day
Afegostat tartrate was administered orally during the 4-week treatment period.
Drug: Afegostat tartrate
Other Names:
  • isofagomine tartrate
  • AT2101

Experimental: Afegostat tartrate 150 mg once per day
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
Drug: Afegostat tartrate
Other Names:
  • isofagomine tartrate
  • AT2101

Experimental: Afegostat tartrate 150 mg once every four days
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
Drug: Afegostat tartrate
Other Names:
  • isofagomine tartrate
  • AT2101

Experimental: Afegostat tartrate 150 mg once every seven days
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
Drug: Afegostat tartrate
Other Names:
  • isofagomine tartrate
  • AT2101




Primary Outcome Measures :
  1. Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (after dosing) through Day 35 ]
    TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through 7 days after the last dose of study drug (Day 35) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.


Secondary Outcome Measures :
  1. Change From Baseline To End Of Treatment In Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC) [ Time Frame: Baseline, Day 28 ]
    GCase is a biomarker used to assess the PD effects of afegostat tartrate. Blood samples were collected to assess GCase levels in WBC. The baseline value was defined as the last non-missing value before the start of study drug.



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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Had a confirmed diagnosis of type 1 Gaucher disease with a known documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase alleles
  • Clinically stable
  • Male or female participants, 18 to 74 years old inclusive
  • All participants of childbearing potential used adequate birth control
  • Provided written informed consent to participate in the study

Exclusion Criteria:

  • Clinically significant disease, severe complications from Gaucher disease, or serious illness that precluded participation in the study in the opinion of the Investigator that compromised the safety of the participant or precluded the participant from completing the study
  • During the screening period, any clinically significant findings, as deemed by the Investigator
  • Partial or total splenectomy (removal of spleen) within the 2 years prior to study entry
  • History of pulmonary hypertension or Gaucher related lung disease
  • History of allergy or sensitivity to the study drug or any excipients, including any prior serious adverse reaction to iminosugars (for example, N-butyldeoxynojirimycin or miglustat)
  • Pregnant or breast-feeding
  • Current/recent drug or alcohol abuse
  • Treatment with any investigational product in the 90 days before study entry
  • Treatment in the previous 90 days with any drug known to have a well-defined potential for toxicity to a major organ
  • Presence or symptoms of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs

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 ClinicalTrials.gov identifier (NCT number): NCT00433147


Locations
United States, California
San Francisco, California, United States, 94143
United States, Florida
Coral Springs, Florida, United States, 33065
United States, Georgia
Decatur, Georgia, United States, 30033
United States, Iowa
Iowa City, Iowa, United States, 52242
United States, New York
New York, New York, United States, 10016
United States, Ohio
Cincinnati, Ohio, United States, 45229
United States, Oregon
Portland, Oregon, United States, 97239
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Houston, Texas, United States, 77030
Sponsors and Collaborators
Amicus Therapeutics
Investigators
Study Director: Medical Monitor, Clinical Research Amicus Therapeutics

Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT00433147     History of Changes
Other Study ID Numbers: GAU-CL-201
First Posted: February 9, 2007    Key Record Dates
Results First Posted: August 15, 2018
Last Update Posted: August 15, 2018
Last Verified: July 2018

Keywords provided by Amicus Therapeutics:
afegostat tartrate
isofagomine tartrate
AT2101
Amicus Therapeutics

Additional relevant MeSH terms:
Gaucher Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders