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A 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.
 
ClinicalTrials.gov Identifier: NCT00214500
Recruitment Status : Completed
First Posted : September 22, 2005
Results First Posted : September 7, 2018
Last Update Posted : October 30, 2018
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Tracking Information
First Submitted Date  ICMJE September 13, 2005
First Posted Date  ICMJE September 22, 2005
Results First Submitted Date  ICMJE August 10, 2018
Results First Posted Date  ICMJE September 7, 2018
Last Update Posted Date October 30, 2018
Actual Study Start Date  ICMJE January 2, 2006
Actual Primary Completion Date January 29, 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 (after dosing) through Week 96 ]
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 96 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
Safety and tolerability of 3 dose levels of oral AT1001
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
  • PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat [ Time Frame: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hr (postdose) ]
    The AUC from time zero to 12 hours (hr) postdose (AUC0-12) was evaluated in plasma following a single dose of migalastat 25, 100, and 250 mg on Days 1, 15, and 29, respectively. In addition, AUC0-12 was assessed following multiple doses (14 days) of migalastat 25, 100, and 250 mg on Days 14, 28, and 42, respectively.
  • α-Galactosidase A (α-Gal A) Activity In Leukocytes At Baseline, Week 12, And Week 96 [ Time Frame: Baseline, Week 12 (end of treatment period), Week 96 (end of extension period) ]
    Leukocytes 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/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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
  • Pharmacokinetics of 3 dose levels of oral AT1001
  • Pharmacodynamic effects of oral AT1001 (effects on enzyme and substrate levels, cardiac function, renal function, and nerve conduction)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
Official Title  ICMJE A Phase 2, Open-Label, Multicenter, 12-Week Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AT1001 in Patients With Fabry Disease
Brief Summary Study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.
Detailed Description

This was a Phase 2, open-label study in male participants with Fabry disease. All participants who met initial eligibility criteria underwent a 28-day screening period, including a 14-day run-in with migalastat (150 milligrams [mg] migalastat once a day [QD] from Days -28 to -15) to assess eligibility for entering the treatment period of the study. Participants who entered the treatment period were required to have α-galactosidase A (α-Gal A) activity responsive to migalastat.

Fifteen participants received at least 1 dose of study drug, however, 6 of these participants did not demonstrate α-Gal A activity responsive to migalastat and were thus screen failures (these participants are hereafter referred to as "dosed screen failures") due to not meeting all inclusion criteria for treatment. Therefore, 9 participants were enrolled into the treatment period (these participants are hereafter referred to as "eligible-enrolled").

Eligible-enrolled participants (those who satisfied the criteria for inclusion in the study) received escalating doses of migalastat twice a day (BID) for 6 weeks (Days 1 to 42), followed by 6 weeks at 1 dose level BID (Days 43 to 84) during the treatment period. Participants could then opt to participate in the extension period. The study consisted of 2 optional extension periods, the first through Week 48 and the second through Week 96. For participants who did not continue into the optional treatment extension, the study included a 2-week follow-up period.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fabry Disease
Intervention  ICMJE Drug: migalastat HCl
Other Names:
  • AT1001
  • Galafold
  • migalastat
Study Arms  ICMJE Experimental: Migalastat

Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods.

Treatment Period:

  • Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14).
  • Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28).
  • Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42).
  • Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84).

Extension Period:

  • Migalastat 25 mg BID for Weeks 12 through 48.
  • Migalastat 50 mg QD for Weeks 48 through 96.
Intervention: Drug: migalastat HCl
Publications * Benjamin ER, Della Valle MC, Wu X, Katz E, Pruthi F, Bond S, Bronfin B, Williams H, Yu J, Bichet DG, Germain DP, Giugliani R, Hughes D, Schiffmann R, Wilcox WR, Desnick RJ, Kirk J, Barth J, Barlow C, Valenzano KJ, Castelli J, Lockhart DJ. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genet Med. 2017 Apr;19(4):430-438. doi: 10.1038/gim.2016.122. Epub 2016 Sep 22.

*   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: August 10, 2018)
9
Original Enrollment  ICMJE
 (submitted: September 14, 2005)
20
Actual Study Completion Date  ICMJE January 29, 2008
Actual Primary Completion Date January 29, 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males between 18 and 55 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
  • In the judgment of the investigator, were either able to safely suspend ERT throughout the study, or be ERT naive
  • 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 >2 mg per deciliter on Day -2
  • Screening 12-lead electrocardiogram 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00214500
Other Study ID Numbers  ICMJE FAB-CL-201 (AA1565520)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amicus Therapeutics
Study Sponsor  ICMJE Amicus Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor, Clinical Research Amicus Therapeutics
PRS Account Amicus Therapeutics
Verification Date October 2018

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