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CompletedNCT01196871Updated Dec 19, 2018Results posted

Drug-Drug Interaction Study Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Participants With Fabry Disease

A Phase 2 interventional study of Migalastat HCl and Agalsidase Beta in Fabry Disease, sponsored by Amicus Therapeutics. Completed at 10 sites in 5 countries. Open to male participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-12-19.

Sponsored by Amicus Therapeutics · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
20
Allocation
Non-randomized
Ages
18 Years to 65 Years
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • Fabry Disease

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Keywords

  • Amicus Therapeutics
  • AT1001
  • Galafold
  • Migalastat
  • Pharmacokinetics
03

In context

Fabry Disease

242 studies on the registry are indexed under Fabry Disease; 54 are open to participants now.

This study's enrollment of 20 is close to the median of 22 across 105 interventional studies indexed under Fabry Disease.

Browse Fabry Disease studies →

Lead sponsor

Amicus Therapeutics is the lead sponsor of 42 studies on the registry; 8 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
Male
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Experimental
    Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg)

    Drug: Migalastat HCl · Biological: Agalsidase Beta

  • Experimental
    Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg)

    Drug: Migalastat HCl · Biological: Agalsidase Beta

  • Experimental
    Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg)

    Drug: Migalastat HCl · Biological: Agalsidase Alfa

  • Experimental
    Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg)

    Drug: Migalastat HCl · Biological: Agalsidase Beta

  • Experimental
    Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg)

    Drug: Migalastat HCl · Biological: Agalsidase Beta

  • Experimental
    Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg)

    Drug: Migalastat HCl · Biological: Agalsidase Alfa

Interventions

  • DrugMigalastat HCl

    Oral capsules, single dose

    Also known as: AT1001, Galafold, migalastat

  • BiologicalAgalsidase Beta

    IV infusion, single dose

    Also known as: Fabrazyme

  • BiologicalAgalsidase Alfa

    IV infusion, single dose

    Also known as: Replagal

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose

  2. 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.

    Time frame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose

  3. 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.

    Time frame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose

  4. 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.

    Time frame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose

  5. 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.

    Time frame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose

  6. 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.

    Time frame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose

  7. 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.

    Time frame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose

  8. 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.

    Time frame: 0 hr, 1 day post dose

  9. 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.

    Time frame: 0 hr, 1 day post dose

  10. 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.

    Time frame: 0 hr, 1 day post dose

Secondary outcomes

  1. 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.

    Time frame: Baseline, Day 7

07

Results

Posted Nov 1, 2018

Participant flow

Stage 1: Period 1
Participant flow — Stage 1: Period 1
MilestoneAgalsidase 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)
Started534000
Pk population534000
Received at least 1 dose of study drug534000
Completed534000
Not completed000000
Stage 1: Period 2
Participant flow — Stage 1: Period 2
MilestoneAgalsidase 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)
Started534000
Pk population534000
Completed534000
Not completed000000
Stage 1: Period 3
Participant flow — Stage 1: Period 3
MilestoneAgalsidase 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)
Started534000
Completed534000
Not completed000000
Stage 2: Period 1
Participant flow — Stage 2: Period 1
MilestoneAgalsidase 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)
Started000254
Received at least 1 dose of study drug000254
Pk population000154
Completed000254
Not completed000000
Stage 2: Period 2
Participant flow — Stage 2: Period 2
MilestoneAgalsidase 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)
Started000164
Pk population000164
Completed000164
Not completed000000

Outcome measures

PrimaryChange 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.

Time frame:
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Reported as:
Mean · hr*[nmol/hr/mL]
Change In Area Under The Plasma Concentration Versus Time Curve (AUC) For Active α-Galactosidase A (α-Gal A) Levels After Administration Of Migalastat
hr*[nmol/hr/mL]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)
Period 1: AUC0-t1132.72 ± 223.2154730.47 ± 1045.068384.20 ± 86.9042409.02 ± NA5670.76 ± 3926.295787.23 ± 509.967
Period 2: AUC0-t3255.09 ± 904.7169541.21 ± 2813.1391602.58 ± 425.7986127.75 ± NA9908.56 ± 3097.7462199.98 ± 875.140
Period 1: AUCinfinity1145.73 ± 217.8944871.66 ± 1242.965388.10 ± 83.7702523.87 ± NA5851.62 ± 4345.407800.38 ± 509.308
Period 2: AUCinfinity3287.09 ± 907.0739765.04 ± 3118.8751626.67 ± 407.5956197.71 ± NA10280.79 ± 3399.3422253.95 ± 859.586
Statistical analysis
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) · Auc0-t ratio: 2.942 · 90% CI 2.439 to 3.548The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) · Aucinfinity ratio: 2.942 · 90% CI 2.431 to 3.560The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) · Auc0-t ratio: 2.354 · 90% CI 1.826 to 3.035The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) · Aucinfinity ratio: 2.375 · 90% CI 1.839 to 3.068The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
PrimaryChange 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.

Time frame:
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Reported as:
Mean · nmol/hr/mL
Change In Maximum Observed Plasma Concentration (Cmax) For Active α-Gal A Levels After Administration Of Migalastat
nmol/hr/mLAgalsidase 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)
Period 1:Cmax514.18 ± 87.4581682.13 ± 407.862309.02 ± 91.568684.36 ± NA1775.12 ± 684.734370.91 ± 113.362
Period 2: Cmax899.93 ± 235.7012400.86 ± 928.257515.34 ± 77.2071351.18 ± NA2413.31 ± 798.090619.00 ± 141.411
Statistical analysis
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) · Cmax ratio: 1.629 · 90% CI 1.440 to 1.843The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) · Cmax ratio: 1.546 · 90% CI 1.300 to 1.838The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
PrimaryChange 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.

Time frame:
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Reported as:
Mean · hr
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
hrAgalsidase 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)
Period 1: tmax2.07 ± 0.1492.16 ± 0.7780.75 ± 0.1703.00 ± NA2.58 ± 0.8010.75 ± 0.170
Period 2: tmax2.30 ± 0.4472.41 ± 0.5260.75 ± 0.1703.00 ± NA2.58 ± 0.8010.75 ± 0.170
Period 1: t1/23.91 ± 2.0545.33 ± 4.0824.48 ± 3.1326.50 ± NA3.11 ± 1.8755.15 ± 3.645
Period 2: t1/23.51 ± 1.3044.30 ± 1.7124.27 ± 1.5363.49 ± NA4.96 ± 1.5325.31 ± 2.462
PrimaryChange 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.

Time frame:
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Reported as:
Mean · hr*[ng/hr/mL]
Change In AUC For Total α-Gal A Protein Levels After Administration Of Migalastat
hr*[ng/hr/mL]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)
Period 1: AUC0-t57187.48 ± 47381.9629905.87 ± 20470.2842256.74 ± 13868.0016229.13 ± NA17200.63 ± 16906.9728770.37 ± 10941.44
Period 2: AUC0-t56895.40 ± 45753.7734298.23 ± 17022.1342528.55 ± 14652.9316272.03 ± NA22031.50 ± 16754.0429816.41 ± 8956.789
Statistical analysis
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) · Auc0-t ratio: 1.025 · 90% CI 0.921 to 1.140The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) · Auc0-t ratio: 1.256 · 90% CI 1.026 to 1.538The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
PrimaryChange 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.

Time frame:
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Reported as:
Mean · percentage of AUC
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
percentage of AUCAgalsidase 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)
Period 160.50 ± 22.24127.55 ± 14.64273.26 ± 13.3248.49 ± NA12.30 ± 15.30758.37 ± 11.065
Period 233.97 ± 31.66217.91 ± 11.09154.06 ± 21.5383.25 ± NA11.90 ± 13.02947.47 ± 18.832
PrimaryChange 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.

Time frame:
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Reported as:
Mean · nmol/hr/mL
Change In Cmax For Total α-Gal A Protein Levels After Administration Of Migalastat
nmol/hr/mLAgalsidase 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)
Period 1: Cmax7159.13 ± 4599.1135156.74 ± 2411.6013813.49 ± 1036.6273141.84 ± NA3983.05 ± 1422.7343587.46 ± 1181.299
Period 2: Cmax7060.29 ± 5016.1475572.63 ± 1915.0734196.18 ± 1264.7632715.38 ± NA4170.15 ± 935.5123773.21 ± 950.710
Statistical analysis
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) · Cmax ratio: 1.034 · 90% CI 0.929 to 1.152The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) · Cmax ratio: 1.063 · 90% CI 0.972 to 1.164The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
PrimaryChange 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.

Time frame:
0 hr, 2 hr, 2 days, 7 days, 14 days post dose
Reported as:
Mean · hr
Change In Tmax And T1/2 For Total α-Gal A Protein Levels After Administration Of Migalastat
hrAgalsidase 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)
Period 1: tmax2.07 ± 0.1492.16 ± 0.7780.75 ± 0.1703.00 ± NA2.50 ± 0.7750.75 ± 0.170
Period 2: tmax2.10 ± 0.5482.24 ± 0.7500.75 ± 0.1663.00 ± NA2.50 ± 0.5480.75 ± 0.170
Period 1: t1/257.78 ± 40.01917.77 ± 8.83786.19 ± 92.0482.96 ± NA6.71 ± 7.70230.32 ± 5.010
Period 2: t1/223.10 ± 22.3389.15 ± 5.62132.95 ± 20.2822.00 ± NA5.55 ± 5.55328.05 ± 18.582
PrimaryChange 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.

Time frame:
0 hr, 1 day post dose
Reported as:
Mean · hr*[ng/hr/mL]
Change In AUC For Migalastat After Administration Of Agalsidase
hr*[ng/hr/mL]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)
Period 2: AUC0-t15717.87 ± 7140.4849413.79 ± 2153.16116051.81 ± 3441.66349483.00 ± NA30450.61 ± 10750.3133920.71 ± 8559.677
Period 3: AUC0-t13009.11 ± 3747.0869285.71 ± 2270.87516011.88 ± 5361.097NA ± NANA ± NANA ± NA
Period 2: AUCinfinity15889.34 ± 7841.9689653.09 ± 2185.03116523.94 ± 3804.01853034.59 ± NA31856.37 ± 11283.9434700.89 ± 8429.954
Period 3: AUCinfinity13708.03 ± 4278.9519597.10 ± 2253.44416586.14 ± 5818.395NA ± NANA ± NANA ± NA
Statistical analysis
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) · Auc0-t ratio: 1.059 · 90% CI 0.818 to 1.371The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) · Aucinfinity ratio: 1.052 · 90% CI 0.807 to 1.371The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
PrimaryChange 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.

Time frame:
0 hr, 1 day post dose
Reported as:
Mean · nmol/hr/mL
Change In Cmax For Migalastat After Administration Of Agalsidase
nmol/hr/mLAgalsidase 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)
Period 2: Cmax1690.00 ± 606.5481295.67 ± 501.6542047.50 ± 192.5924750.00 ± NA3763.33 ± 984.5744455.00 ± 1840.697
Period 3: Cmax1634.00 ± 396.0811374.00 ± 574.1322035.00 ± 512.803NA ± NANA ± NANA ± NA
Statistical analysis
  • Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) vs Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) vs Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) · Cmax ratio: 0.997 · 90% CI 0.791 to 1.259The ratios of the geometric means (combination/alone) and its 90% CI are obtained by exponentiating the least squares mean difference and its 90% CI of the natural log-transformed data.
PrimaryChange 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.

Time frame:
0 hr, 1 day post dose
Reported as:
Mean · hr
Change In Tmax And T1/2 For Migalastat After Administration Of Agalsidase
hrAgalsidase 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)
Period 2: tmax3.70 ± 0.6513.33 ± 0.5773.02 ± 0.8184.00 ± NA3.33 ± 1.1024.50 ± 1.000
Period 3: tmax3.03 ± 0.7103.00 ± 0.0003.03 ± 0.050NA ± NANA ± NANA ± NA
Period 2: t1/25.39 ± 1.0984.95 ± 0.3354.86 ± 0.8316.36 ± NA4.87 ± 1.2024.44 ± 1.328
Period 3: t1/25.31 ± 1.2415.05 ± 0.5584.81 ± 0.601NA ± NANA ± NANA ± NA
SecondaryChange 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.

Time frame:
Baseline, Day 7
Reported as:
Mean · pmol/mg/hr
Change From Baseline To Day 7 In Active α-Gal A In Skin Following Treatment With Agalsidase Alone And Co-administration With Migalastat
pmol/mg/hrAgalsidase 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)
Period 1: Day 2334 (-141 to 998)857 (795 to 919)121 (-52 to 371)89 (NA to NA)1936 (884 to 3162)18 (NA to NA)
Period 2: Day 21508 (221 to 4103)2977 (NA to NA)437 (35 to 1146)647 (NA to NA)4019 (1777 to 6168)160 (NA to NA)
Period 1: Day 7137 (45 to 234)553 (315 to 791)139 (50 to 229)72 (NA to NA)613 (252 to 2001)—
Period 2: Day 7574 (-200 to 2588)855 (460 to 1250)228 (11 to 606)235 (NA to NA)789 (-174 to 1935)-100 (NA to NA)

Adverse events

Collected over Adverse events (AEs) were monitored up to 5.5 months after the first dose of study drug. For Period (Pd) 1 and 2 of Stages 1 and 2, AEs were reported starting 1 day prior (Day -1) to the first dose of study drug (Agalsidase Beta [Agal-B] or Agalsidase Alfa [Agal-A]) to 1 month after the last dose of study drug. For Pd 3 of Stage 1, AEs were reported starting on the day of the first dose of study drug (Day 1) to 1 month after the last dose of study drug (Migalastat [Mig]).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Stage 1 Pd 1: 0.5 mg/kg Agal-B (Arm 1)—0/5 (0%)4/5 (80%)
Stage 1 Pd 2: 150 mg Mig Before 0.5 mg/kg Agal-B (Arm 1)—0/5 (0%)0/5 (0%)
Stage 1 Pd 3: 150 mg Mig (Arm 1)—0/5 (0%)3/5 (60%)
Stage 1 Pd 1: 1.0 mg/kg Agal-B (Arm 2)—0/3 (0%)3/3 (100%)
Stage 1 Pd 2: 150 mg Mig Before 1.0 mg/kg Agal-B (Arm 2)—0/3 (0%)2/3 (66.7%)
Stage 1 Pd 3: 150 mg Mig (Arm 2)—0/3 (0%)0/3 (0%)
Stage 1 Pd 1: 0.2 mg/kg Agal-A (Arm 3)—0/4 (0%)1/4 (25%)
Stage 1 Pd 2: 150 mg Mig Before 0.2 mg/kg Agal-A (Arm 3)—0/4 (0%)0/4 (0%)
Stage 1 Pd 3: 150 mg Mig (Arm 3)—0/4 (0%)2/4 (50%)
Stage 2 Pd 1: 0.5 mg/kg Agal-B (Arm 4)—1/2 (50%)1/2 (50%)
Stage 2 Pd 2: 450 mg Mig Before 0.5 mg/kg Agal-B (Arm 4)—0/1 (0%)0/1 (0%)
Stage 2 Pd 1: 1.0 mg/kg Agal-B (Arm 5)—0/6 (0%)1/6 (16.7%)
Stage 2 Pd 2: 450 Mig Before 1.0 mg/kg Agal-B (Arm 5)—0/6 (0%)1/6 (16.7%)
Stage 2 Pd 1: 0.2 mg/kg Agal-A (Arm 6)—0/4 (0%)3/4 (75%)
Stage 2 Pd 2: 450 Mig Before 0.2 mg/kg Agal-A (Arm 6)—0/4 (0%)4/4 (100%)
Most frequent serious events
Most frequent serious events
EventStage 1 Pd 1: 0.5 mg/kg Agal-B (Arm 1)Stage 1 Pd 2: 150 mg Mig Before 0.5 mg/kg Agal-B (Arm 1)Stage 1 Pd 3: 150 mg Mig (Arm 1)Stage 1 Pd 1: 1.0 mg/kg Agal-B (Arm 2)Stage 1 Pd 2: 150 mg Mig Before 1.0 mg/kg Agal-B (Arm 2)Stage 1 Pd 3: 150 mg Mig (Arm 2)Stage 1 Pd 1: 0.2 mg/kg Agal-A (Arm 3)Stage 1 Pd 2: 150 mg Mig Before 0.2 mg/kg Agal-A (Arm 3)Stage 1 Pd 3: 150 mg Mig (Arm 3)Stage 2 Pd 1: 0.5 mg/kg Agal-B (Arm 4)Stage 2 Pd 2: 450 mg Mig Before 0.5 mg/kg Agal-B (Arm 4)Stage 2 Pd 1: 1.0 mg/kg Agal-B (Arm 5)Stage 2 Pd 2: 450 Mig Before 1.0 mg/kg Agal-B (Arm 5)Stage 2 Pd 1: 0.2 mg/kg Agal-A (Arm 6)Stage 2 Pd 2: 450 Mig Before 0.2 mg/kg Agal-A (Arm 6)
AcroparaesthesiaNervous system disorders0/50/50/50/30/30/30/40/40/41/20/10/60/60/40/4
Most frequent other events
Showing 10 of 54
Most frequent other events
EventStage 1 Pd 1: 0.5 mg/kg Agal-B (Arm 1)Stage 1 Pd 2: 150 mg Mig Before 0.5 mg/kg Agal-B (Arm 1)Stage 1 Pd 3: 150 mg Mig (Arm 1)Stage 1 Pd 1: 1.0 mg/kg Agal-B (Arm 2)Stage 1 Pd 2: 150 mg Mig Before 1.0 mg/kg Agal-B (Arm 2)Stage 1 Pd 3: 150 mg Mig (Arm 2)Stage 1 Pd 1: 0.2 mg/kg Agal-A (Arm 3)Stage 1 Pd 2: 150 mg Mig Before 0.2 mg/kg Agal-A (Arm 3)Stage 1 Pd 3: 150 mg Mig (Arm 3)Stage 2 Pd 1: 0.5 mg/kg Agal-B (Arm 4)Stage 2 Pd 2: 450 mg Mig Before 0.5 mg/kg Agal-B (Arm 4)Stage 2 Pd 1: 1.0 mg/kg Agal-B (Arm 5)Stage 2 Pd 2: 450 Mig Before 1.0 mg/kg Agal-B (Arm 5)Stage 2 Pd 1: 0.2 mg/kg Agal-A (Arm 6)Stage 2 Pd 2: 450 Mig Before 0.2 mg/kg Agal-A (Arm 6)
VomitingGastrointestinal disorders0/50/50/50/30/30/31/40/40/41/20/11/60/60/40/4
Tinea capitisInfections and infestations0/50/50/50/30/30/30/40/40/41/20/10/60/60/40/4
Melanocytic naevusNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/50/50/50/30/30/30/40/40/41/20/10/60/60/40/4
Dry skinSkin and subcutaneous tissue disorders0/50/50/50/30/30/30/40/40/41/20/10/60/60/40/4
LymphoedemaVascular disorders0/50/50/50/30/30/30/40/40/41/20/10/60/60/40/4
Fabry's diseaseCongenital, familial and genetic disorders0/50/50/50/30/30/30/40/40/41/20/10/60/60/40/4
Cardiac murmurInvestigations2/50/50/50/30/30/30/40/40/40/20/10/60/60/40/4
Angina pectorisCardiac disorders0/50/50/50/31/30/30/40/40/40/20/10/60/60/40/4
Supraventricular extrasystolesCardiac disorders0/50/50/51/30/30/30/40/40/40/20/10/60/60/40/4
DiarrhoeaGastrointestinal disorders0/50/50/50/31/30/30/40/40/40/20/10/60/61/41/4

Baseline characteristics

Safety Population: all participants who received at least 1 dose of agalsidase or migalastat. All safety analyses were performed using this set. Participants were analyzed according to treatment received. Three participants from Stage 1 were re-enrolled and newly identified in Stage 2, with 1 receiving both 0.5 and 1.0 mg/kg agalsidase beta.

Age, Continuous
Age, Continuous(years)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)Total
Stage 150.6 ± 6.8845.7 ± 8.0243.5 ± 5.07———47.0 ± 6.84
Stage 2———53.5 ± 2.1238.7 ± 12.1638.5 ± 9.1540.1 ± 11.11
Sex: Female, Male
Sex: Female, Male(Participants)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)Total
Stage 1 — Female000———0
Stage 1 — Male534———12
Stage 2 — Female———0000
Stage 2 — Male———26412
08

Study locations

10 sites
  • Birmingham, Alabama 35294, United States
  • Decatur, Georgia 30033, United States
  • Iowa City, Iowa 52242, United States
  • Kansas City, Kansas 66160, United States
  • Springfield, Virginia 22152, United States
  • Nedlands, Australia
  • Parkville, Australia
  • Edegem, Belgium
  • Montreal, Canada
  • Amsterdam, Netherlands
09

References and documents

Publications

  • 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. PubMed 26252393 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 19, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01196871
Lead sponsor
Amicus Therapeutics
Responsible party
Sponsor
First posted
Sep 9, 2010
Start date
Feb 2, 2011
Primary completion
Oct 9, 2012
Completion
Oct 9, 2012
Results posted
Nov 1, 2018
Last update
Dec 19, 2018

Study contacts

Medical Monitor Clinical Research
study director · Amicus Therapeutics

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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