Back to resultsDrug-Drug Interaction Study Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Participants With Fabry Disease
Primary Purpose
Fabry Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Migalastat HCl
Agalsidase Beta
Agalsidase Alfa
Sponsored by
About this trial
This is an interventional treatment trial for Fabry Disease focused on measuring Amicus Therapeutics, AT1001, Galafold, Migalastat, Pharmacokinetics
Eligibility Criteria
Inclusion Criteria:
- Male diagnosed with Fabry disease and between 18 and 65 years of age, inclusive
- Body mass index between 18-35 kg per meter squared
- Had initiated treatment with agalsidase at least 1 month prior to screening, and had received at least 2 infusions before screening
- Had stable dose level, dosing regimen, and form of agalsidase for at least 1 month before screening
- Had an estimated creatinine clearance greater than or equal to 50 milliliters (mL)/minute at screening
- Agreed to use medically accepted methods of contraception during the study and for 30 days after study completion
- Were willing and able to provide written informed consent
Exclusion Criteria:
- Had a documented transient ischemic attack, ischemic stroke, unstable angina, or myocardial infarction within the 3 months before screening
- Had clinically significant unstable cardiac disease (for example, cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or New York Heart Association class III or IV congestive heart failure)
- History of allergy or sensitivity to study drug (including excipients) or other iminosugars (such as miglustat, miglitol)
- Required a concomitant medication prohibited by the protocol: Glyset® (miglitol), or Zavesca® (miglustat)
- Any investigational/experimental drug or device within 30 days of screening, except for use of investigational enzyme replacement therapy for Fabry disease
- Had any intercurrent illness or condition that might have precluded the participant from fulfilling the protocol requirements or suggested to the investigator that the potential participant might have had an unacceptable risk by participating in this study
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg)
Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg)
Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg)
Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg)
Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg)
Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg)
Arm Description
Outcomes
Primary Outcome Measures
Change In Area Under The Plasma Concentration Versus Time Curve (AUC) For Active α-Galactosidase A (α-Gal A) Levels After Administration Of Migalastat
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the active α-Gal A enzyme level in plasma using a qualified assay that measured the rate of enzyme activity using an artificial, fluorescent substrate. The agalsidase plasma PK parameter values for AUC extrapolated from time 0 to infinity (AUCinfinity) and AUC to the last time point at which concentration is quantified (AUC0-t) are reported in hr*[nanomoles/hr/milliliter] (hr*[nmol/hr/mL]). In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Change In Maximum Observed Plasma Concentration (Cmax) For Active α-Gal A Levels After Administration Of Migalastat
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the active α-Gal A enzyme level in plasma using a qualified assay that measured the rate of enzyme activity using an artificial, fluorescent substrate. The agalsidase plasma PK parameter value for Cmax is reported in nmol/hr/mL. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Change In Time To Maximum Observed Plasma Concentration (Tmax) And Terminal Elimination Half-life (T1/2) For Active α-Gal A Levels After Administration Of Migalastat
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the active α-Gal A enzyme level in plasma using a qualified assay that measured the rate of enzyme activity using an artificial, fluorescent substrate. The agalsidase plasma PK parameter values for tmax and t1/2 are reported in hr. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Change In AUC For Total α-Gal A Protein Levels After Administration Of Migalastat
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the α-Gal A protein level in plasma by Western blot using anti-human Gal A antibody. The agalsidase plasma PK parameter value for AUC0-t is reported in hr*[nanogram (ng)/hr/mL]. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Change In Percentage Of AUCinfinity Extrapolated From The Last Time Point At Which Concentration Is Quantified To Infinity (AUCextrapolated %) For Total α-Gal A Protein Levels After Administration Of Migalastat
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the α-Gal A protein level by Western blot using anti-human Gal A antibody. The agalsidase plasma PK parameter values for AUCextrapolated % are reported. AUCextrapolated % is reported instead of AUCinfinity because small but quantifiable concentrations of α-Gal A protein past 24 hr post-dose extrapolated to infinity comprised >50% of total AUC in most participants and were unevaluable. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hour after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Change In Cmax For Total α-Gal A Protein Levels After Administration Of Migalastat
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the α-Gal A protein level in plasma by Western blot using anti-human Gal A antibody. The agalsidase plasma PK parameter values for Cmax is reported in nmol/hr/mL. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Change In Tmax And T1/2 For Total α-Gal A Protein Levels After Administration Of Migalastat
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the total α-Gal A protein level in plasma by Western blot using anti-human Gal A antibody. The agalsidase plasma PK parameter values for tmax and t1/2 are reported in hr. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Change In AUC For Migalastat After Administration Of Agalsidase
This measure characterized the effects of agalsidase on the plasma PK of migalastat using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay. The migalastat plasma PK parameter values for AUCinfinity and AUC0-t are reported in hr*[ng/hr/mL]. In Period 2 of Stages 1 and 2, blood samples were collected: just before dosing with migalastat (2 hr prior to the agalsidase infusion) and at 1 hr after migalastat dosing; immediately before the agalsidase infusion and over a 24-hr period after infusion. In Period 3 (Stage 1 only), blood samples were collected before dosing and over the 24-hr period after administration of migalastat.
Change In Cmax For Migalastat After Administration Of Agalsidase
This measure characterized the effects of agalsidase on the plasma PK of migalastat using a validated liquid LC-MS assay. The migalastat plasma PK parameter values for Cmax are reported in nmol/hr/mL. In Period 2 of Stages 1 and 2, blood samples were collected: just before dosing with migalastat (2 hr prior to the agalsidase infusion) and at 1 hr after migalastat dosing; immediately before the agalsidase infusion and over a 24-hr period after infusion. In Period 3 (Stage 1 only), blood samples were collected before dosing and over the 24-hr period after administration of migalastat.
Change In Tmax And T1/2 For Migalastat After Administration Of Agalsidase
This measure characterized the effects of agalsidase on the plasma PK of migalastat using a validated LC-MS assay. The migalastat plasma PK parameter values for tmax and t1/2 are reported in hr. In Period 2 of Stages 1 and 2, blood samples were collected: just before dosing with migalastat (2 hr prior to the agalsidase infusion) and at 1 hr after migalastat dosing; immediately before the agalsidase infusion and over a 24-hr period after infusion. In Period 3 (Stage 1 only), blood samples were collected before dosing and over the 24-hr period after administration of migalastat.
Secondary Outcome Measures
Change From Baseline To Day 7 In Active α-Gal A In Skin Following Treatment With Agalsidase Alone And Co-administration With Migalastat
This measure characterized the effects of agalsidase and migalastat on α-Gal A activity in the skin using a qualified assay that measured the rate of enzyme activity using an artificial, fluorescent substrate. Baseline was defined as Day 1/Period 1 pre-infusion level. α-Gal A activity is reported in picomoles/mg/hr (pmol/mg/hr). Biopsy samples were obtained: on Day -1/Period 1; 24 hr after initiation of the infusion during Period 1 and Period 2; on Day 7 of Period 1 and Period 2.
Full Information
NCT ID
NCT01196871
First Posted
September 7, 2010
Last Updated
November 29, 2018
Sponsor
Amicus Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT01196871
Brief Title
Drug-Drug Interaction Study Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Participants With Fabry Disease
Official Title
An Open-label Phase 2A Study to Investigate Drug-Drug Interactions Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Subjects With Fabry Disease
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
February 2, 2011 (Actual)
Primary Completion Date
October 9, 2012 (Actual)
Study Completion Date
October 9, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amicus Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The objective was to determine the effects of a single dose of migalastat hydrochloride (HCl) (migalastat) 150 and 450 milligrams (mg) on the safety and plasma pharmacokinetics (PK) of agalsidase and the effects of agalsidase on the safety and PK of migalastat 150 mg.
Detailed Description
This open-label study was conducted in 2 stages (Stage 1, Stage 2). Stage 1 included migalastat 150 mg; Stage 2 included migalastat 450 mg. Each dose of migalastat was selected to evaluate interaction with each of 3 doses of recombinant agalsidase: 0.5 mg/kilogram (kg) agalsidase beta; 1.0 mg/kg agalsidase beta; 0.2 mg/kg agalsidase alfa.
Migalastat was administered orally. Agalsidase alfa was administered as a 40-minute intravenous (IV) infusion and agalsidase beta was administered as a 2-hour (hr) IV infusion.
Stage 1 consisted of 3 treatment periods with 14 days intervening between each period.
Period 1, Day 1: agalsidase was administered alone.
Period 2, Day 1: migalastat was administered, followed 2 hrs later by agalsidase.
Period 3, Day 7: migalastat was administered alone.
Stage 2 consisted of two 14-day treatment periods in which the plasma exposure of migalastat was characterized when migalastat was administered with agalsidase solely to confirm the attainment of adequate migalastat plasma concentrations.
Period 1, Day 1: agalsidase was administered as an IV infusion using a calibrated infusion pump.
Period 2, Day 1: migalastat was administered, followed 2 hrs later by agalsidase.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease
Keywords
Amicus Therapeutics, AT1001, Galafold, Migalastat, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
A 2-stage design was used to study the effects of 2 dose levels of migalastat, while a 2- or 3-period design within each stage enabled study of the effects of one drug on the PK, pharmacodynamics, and safety of the other drug.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg)
Arm Type
Experimental
Arm Title
Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg)
Arm Type
Experimental
Arm Title
Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg)
Arm Type
Experimental
Arm Title
Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg)
Arm Type
Experimental
Arm Title
Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg)
Arm Type
Experimental
Arm Title
Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Migalastat HCl
Other Intervention Name(s)
AT1001, Galafold, migalastat
Intervention Description
Oral capsules, single dose
Intervention Type
Biological
Intervention Name(s)
Agalsidase Beta
Other Intervention Name(s)
Fabrazyme
Intervention Description
IV infusion, single dose
Intervention Type
Biological
Intervention Name(s)
Agalsidase Alfa
Other Intervention Name(s)
Replagal
Intervention Description
IV infusion, single dose
Primary Outcome Measure Information:
Title
Change In Area Under The Plasma Concentration Versus Time Curve (AUC) For Active α-Galactosidase A (α-Gal A) Levels After Administration Of Migalastat
Description
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the active α-Gal A enzyme level in plasma using a qualified assay that measured the rate of enzyme activity using an artificial, fluorescent substrate. The agalsidase plasma PK parameter values for AUC extrapolated from time 0 to infinity (AUCinfinity) and AUC to the last time point at which concentration is quantified (AUC0-t) are reported in hr*[nanomoles/hr/milliliter] (hr*[nmol/hr/mL]). In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Time Frame
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Title
Change In Maximum Observed Plasma Concentration (Cmax) For Active α-Gal A Levels After Administration Of Migalastat
Description
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the active α-Gal A enzyme level in plasma using a qualified assay that measured the rate of enzyme activity using an artificial, fluorescent substrate. The agalsidase plasma PK parameter value for Cmax is reported in nmol/hr/mL. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Time Frame
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Title
Change In Time To Maximum Observed Plasma Concentration (Tmax) And Terminal Elimination Half-life (T1/2) For Active α-Gal A Levels After Administration Of Migalastat
Description
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the active α-Gal A enzyme level in plasma using a qualified assay that measured the rate of enzyme activity using an artificial, fluorescent substrate. The agalsidase plasma PK parameter values for tmax and t1/2 are reported in hr. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Time Frame
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Title
Change In AUC For Total α-Gal A Protein Levels After Administration Of Migalastat
Description
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the α-Gal A protein level in plasma by Western blot using anti-human Gal A antibody. The agalsidase plasma PK parameter value for AUC0-t is reported in hr*[nanogram (ng)/hr/mL]. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Time Frame
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Title
Change In Percentage Of AUCinfinity Extrapolated From The Last Time Point At Which Concentration Is Quantified To Infinity (AUCextrapolated %) For Total α-Gal A Protein Levels After Administration Of Migalastat
Description
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the α-Gal A protein level by Western blot using anti-human Gal A antibody. The agalsidase plasma PK parameter values for AUCextrapolated % are reported. AUCextrapolated % is reported instead of AUCinfinity because small but quantifiable concentrations of α-Gal A protein past 24 hr post-dose extrapolated to infinity comprised >50% of total AUC in most participants and were unevaluable. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hour after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Time Frame
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Title
Change In Cmax For Total α-Gal A Protein Levels After Administration Of Migalastat
Description
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the α-Gal A protein level in plasma by Western blot using anti-human Gal A antibody. The agalsidase plasma PK parameter values for Cmax is reported in nmol/hr/mL. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Time Frame
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Title
Change In Tmax And T1/2 For Total α-Gal A Protein Levels After Administration Of Migalastat
Description
This measure characterized the effects of migalastat on the plasma PK of agalsidase by measurement of the total α-Gal A protein level in plasma by Western blot using anti-human Gal A antibody. The agalsidase plasma PK parameter values for tmax and t1/2 are reported in hr. In Period 1 of Stages 1 and 2, blood samples were collected: immediately before the agalsidase infusion and over a 24-hr period after infusion; on Days 2, 7, and 14. In Period 2 of Stages 1 and 2, blood samples were collected: prior to dosing with migalastat (2 hr prior to the agalsidase infusion) and 1 hr after migalastat dosing; immediately before initiation of the agalsidase infusion and over a 24-hr period after initiation of the agalsidase infusion; on Days 2, 7, and 14.
Time Frame
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Title
Change In AUC For Migalastat After Administration Of Agalsidase
Description
This measure characterized the effects of agalsidase on the plasma PK of migalastat using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay. The migalastat plasma PK parameter values for AUCinfinity and AUC0-t are reported in hr*[ng/hr/mL]. In Period 2 of Stages 1 and 2, blood samples were collected: just before dosing with migalastat (2 hr prior to the agalsidase infusion) and at 1 hr after migalastat dosing; immediately before the agalsidase infusion and over a 24-hr period after infusion. In Period 3 (Stage 1 only), blood samples were collected before dosing and over the 24-hr period after administration of migalastat.
Time Frame
0 hr, 1 day post dose
Title
Change In Cmax For Migalastat After Administration Of Agalsidase
Description
This measure characterized the effects of agalsidase on the plasma PK of migalastat using a validated liquid LC-MS assay. The migalastat plasma PK parameter values for Cmax are reported in nmol/hr/mL. In Period 2 of Stages 1 and 2, blood samples were collected: just before dosing with migalastat (2 hr prior to the agalsidase infusion) and at 1 hr after migalastat dosing; immediately before the agalsidase infusion and over a 24-hr period after infusion. In Period 3 (Stage 1 only), blood samples were collected before dosing and over the 24-hr period after administration of migalastat.
Time Frame
0 hr, 1 day post dose
Title
Change In Tmax And T1/2 For Migalastat After Administration Of Agalsidase
Description
This measure characterized the effects of agalsidase on the plasma PK of migalastat using a validated LC-MS assay. The migalastat plasma PK parameter values for tmax and t1/2 are reported in hr. In Period 2 of Stages 1 and 2, blood samples were collected: just before dosing with migalastat (2 hr prior to the agalsidase infusion) and at 1 hr after migalastat dosing; immediately before the agalsidase infusion and over a 24-hr period after infusion. In Period 3 (Stage 1 only), blood samples were collected before dosing and over the 24-hr period after administration of migalastat.
Time Frame
0 hr, 1 day post dose
Secondary Outcome Measure Information:
Title
Change From Baseline To Day 7 In Active α-Gal A In Skin Following Treatment With Agalsidase Alone And Co-administration With Migalastat
Description
This measure characterized the effects of agalsidase and migalastat on α-Gal A activity in the skin using a qualified assay that measured the rate of enzyme activity using an artificial, fluorescent substrate. Baseline was defined as Day 1/Period 1 pre-infusion level. α-Gal A activity is reported in picomoles/mg/hr (pmol/mg/hr). Biopsy samples were obtained: on Day -1/Period 1; 24 hr after initiation of the infusion during Period 1 and Period 2; on Day 7 of Period 1 and Period 2.
Time Frame
Baseline, Day 7
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male diagnosed with Fabry disease and between 18 and 65 years of age, inclusive
Body mass index between 18-35 kg per meter squared
Had initiated treatment with agalsidase at least 1 month prior to screening, and had received at least 2 infusions before screening
Had stable dose level, dosing regimen, and form of agalsidase for at least 1 month before screening
Had an estimated creatinine clearance greater than or equal to 50 milliliters (mL)/minute at screening
Agreed to use medically accepted methods of contraception during the study and for 30 days after study completion
Were willing and able to provide written informed consent
Exclusion Criteria:
Had a documented transient ischemic attack, ischemic stroke, unstable angina, or myocardial infarction within the 3 months before screening
Had clinically significant unstable cardiac disease (for example, cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or New York Heart Association class III or IV congestive heart failure)
History of allergy or sensitivity to study drug (including excipients) or other iminosugars (such as miglustat, miglitol)
Required a concomitant medication prohibited by the protocol: Glyset® (miglitol), or Zavesca® (miglustat)
Any investigational/experimental drug or device within 30 days of screening, except for use of investigational enzyme replacement therapy for Fabry disease
Had any intercurrent illness or condition that might have precluded the participant from fulfilling the protocol requirements or suggested to the investigator that the potential participant might have had an unacceptable risk by participating in this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor Clinical Research
Organizational Affiliation
Amicus Therapeutics
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
City
Springfield
State/Province
Virginia
ZIP/Postal Code
22152
Country
United States
City
Nedlands
Country
Australia
City
Parkville
Country
Australia
City
Edegem
Country
Belgium
City
Montreal
Country
Canada
City
Amsterdam
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
26252393
Citation
Warnock DG, Bichet DG, Holida M, Goker-Alpan O, Nicholls K, Thomas M, Eyskens F, Shankar S, Adera M, Sitaraman S, Khanna R, Flanagan JJ, Wustman BA, Barth J, Barlow C, Valenzano KJ, Lockhart DJ, Boudes P, Johnson FK. Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active alpha-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase. PLoS One. 2015 Aug 7;10(8):e0134341. doi: 10.1371/journal.pone.0134341. eCollection 2015.
Results Reference
result
Learn more about this trial
Drug-Drug Interaction Study Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Participants With Fabry Disease
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