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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) | Experimental |
| |
| Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) | Experimental |
| |
| Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Experimental |
| |
| Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Experimental |
| |
| Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Experimental |
| |
| Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Migalastat HCl | Drug | Oral capsules, single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
| 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. | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor Clinical Research | Amicus Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | 35294 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26252393 | Result | 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. |
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The total number of unique participants in this study was 20: 3 from Stage 1 were re-enrolled and newly identified in Stage 2. Of those, 1 initially received 0.5 milligrams (mg)/kilogram (kg) agalsidase beta; after resolution of an agalsidase beta shortage, their dose was increased to 1.0 mg/kg; all remaining visits were completed at this dose.
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| ID | Title | Description |
|---|---|---|
| FG000 | Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat hydrochloride (HCl) (migalastat) 2 hours (hr) before initiation of an intravenous (IV) infusion of 0.5 mg/kg mg/kg agalsidase beta. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Stage 1: Period 1 |
|
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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.
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| Agalsidase Beta | Biological | IV infusion, single dose |
|
|
| Agalsidase Alfa | Biological | IV infusion, single dose |
|
|
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.
| 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
| 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. | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
| 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. | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
| 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. | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
| 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. | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
| 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. | 0 hr, 1 day post dose |
| 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. | 0 hr, 1 day post dose |
| 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. | 0 hr, 1 day post dose |
| Baseline, Day 7 |
| 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 |
| Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) |
Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| FG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| FG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450 mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| FG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450 mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| FG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450 mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| PK Population | Participants with evaluable PK data who successfully completed at least Period 1 and 2 in any stage |
|
| Received at Least 1 Dose of Study Drug | Safety Population |
|
| COMPLETED |
|
| NOT COMPLETED |
|
| Stage 1: Period 2 |
|
| Stage 1: Period 3 |
|
| Stage 2: Period 1 |
|
| Stage 2: Period 2 |
|
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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| BG001 | Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| BG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| BG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| BG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| BG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | The total number of unique participants in this study was 20: 3 from Stage 1 were re-enrolled and newly identified in Stage 2. The total number of participants in Stage 2 was 11. One participant received both 0.5 and 1.0 mg/kg agalsidase beta (450 mg migalastat) in Stage 2 and appears under both treatment groups. | Mean | Standard Deviation | years |
| |||||||||
| Sex: Female, Male | The total number of unique participants in this study was 20: 3 from Stage 1 were re-enrolled and newly identified in Stage 2. The total number of participants in Stage 2 was 11. One participant received both 0.5 and 1.0 mg/kg agalsidase beta (450 mg migalastat) in Stage 2 and appears under both treatment groups. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | hr*[nmol/hr/mL] | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
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| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | nmol/hr/mL | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
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| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | hr | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
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| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | hr*[ng/hr/mL] | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
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| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | percentage of AUC | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
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| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | nmol/hr/mL | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
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| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | hr | 0 hr, 2 hr, 2 days, 7 days, 14 days post dose |
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| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | hr*[ng/hr/mL] | 0 hr, 1 day post dose |
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| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | nmol/hr/mL | 0 hr, 1 day post dose |
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| Primary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Standard Deviation | hr | 0 hr, 1 day post dose |
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| Secondary | 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. | PK Population: all participants with evaluable PK parameter data who had successfully completed at least Period 1 and Period 2 in any stage. All PK analyses were performed using the PK population. | Posted | Mean | Full Range | pmol/mg/hr | Baseline, Day 7 |
|
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]).
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stage 1 Pd 1: 0.5 mg/kg Agal-B (Arm 1) | Period 1 of Stage 1 consisted of IV administration of 0.5 mg/kg agalsidase beta. | 0 | 5 | 4 | 5 | ||
| EG001 | Stage 1 Pd 2: 150 mg Mig Before 0.5 mg/kg Agal-B (Arm 1) | Period 2 of Stage 1 consisted of administration of a single 150-mg oral dose of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. | 0 | 5 | 0 | 5 | ||
| EG002 | Stage 1 Pd 3: 150 mg Mig (Arm 1) | Period 3 of Stage 1 consisted of a single 150-mg oral dose of migalastat HCl. | 0 | 5 | 3 | 5 | ||
| EG003 | Stage 1 Pd 1: 1.0 mg/kg Agal-B (Arm 2) | Period 1 of Stage 1 consisted of IV administration of 1.0 mg/kg agalsidase beta. | 0 | 3 | 3 | 3 | ||
| EG004 | Stage 1 Pd 2: 150 mg Mig Before 1.0 mg/kg Agal-B (Arm 2) | Period 2 of Stage 1 consisted of administration of a single 150-mg oral dose of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. | 0 | 3 | 2 | 3 | ||
| EG005 | Stage 1 Pd 3: 150 mg Mig (Arm 2) | Period 3 of Stage 1 consisted of a single 150-mg oral dose of migalastat HCl. | 0 | 3 | 0 | 3 | ||
| EG006 | Stage 1 Pd 1: 0.2 mg/kg Agal-A (Arm 3) | Period 1 of Stage 1 consisted of IV administration of 0.2 mg/kg agalsidase alfa. | 0 | 4 | 1 | 4 | ||
| EG007 | Stage 1 Pd 2: 150 mg Mig Before 0.2 mg/kg Agal-A (Arm 3) | Period 2 of Stage 1 consisted of administration a single 150-mg oral dose of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. | 0 | 4 | 0 | 4 | ||
| EG008 | Stage 1 Pd 3: 150 mg Mig (Arm 3) | Period 3 of Stage 1 consisted of a single 150-mg oral dose of migalastat HCl. | 0 | 4 | 2 | 4 | ||
| EG009 | Stage 2 Pd 1: 0.5 mg/kg Agal-B (Arm 4) | Period 1 of Stage 2 consisted of IV administration of 0.5 mg/kg agalsidase beta. | 1 | 2 | 1 | 2 | ||
| EG010 | Stage 2 Pd 2: 450 mg Mig Before 0.5 mg/kg Agal-B (Arm 4) | Period 2 of Stage 2 consisted of a single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before IV administration of 0.5 mg/kg agalsidase beta. | 0 | 1 | 0 | 1 | ||
| EG011 | Stage 2 Pd 1: 1.0 mg/kg Agal-B (Arm 5) | Period 1 of Stage 2 consisted of IV administration of 0.5 mg/kg agalsidase beta. | 0 | 6 | 1 | 6 | ||
| EG012 | Stage 2 Pd 2: 450 Mig Before 1.0 mg/kg Agal-B (Arm 5) | Period 2 of Stage 2 consisted of a single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before IV administration of 1.0 mg/kg agalsidase beta. | 0 | 6 | 1 | 6 | ||
| EG013 | Stage 2 Pd 1: 0.2 mg/kg Agal-A (Arm 6) | Period 1 of Stage 2 consisted of IV administration of 0.2 mg/kg agalsidase alfa. | 0 | 4 | 3 | 4 | ||
| EG014 | Stage 2 Pd 2: 450 Mig Before 0.2 mg/kg Agal-A (Arm 6) | Period 2 of Stage 2 consisted of a single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before IV administration of 0.2 mg/kg agalsidase alfa. | 0 | 4 | 4 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acroparaesthesia | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial flutter | Cardiac disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Supraventricular extrasystoles | Cardiac disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Ear canal erythema | Ear and labyrinth disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Tympanic membrane disorder | Ear and labyrinth disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Ear Pain | Ear and labyrinth disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Faeces pale | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Vessel puncture site haematoma | General disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
| |
| Heart sounds abnormal | Investigations | MedDRA 15.0 | Systematic Assessment |
| |
| Lymph node palpable | Investigations | MedDRA 15.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
| |
| Scar | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Tinea capitis | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
| |
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Amaurosis fugax | Eye disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
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| Incision site blister | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
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| Chest discomfort | General disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 15.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
| |
| Aggression | Psychiatric disorders | MedDRA 15.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 15.0 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Systematic Assessment |
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| Hyperventilation | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Systematic Assessment |
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| Fabry's disease | Congenital, familial and genetic disorders | MedDRA 15.0 | Systematic Assessment |
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| Cardiac murmur | Investigations | MedDRA 15.0 | Systematic Assessment |
|
The investigator can only publish the results from this trial provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review. If requested, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Amicus Therapeutics | Medical Affairs | +1-877-426-4287 (877-4-AMICUS) | MedInfoUSA@amicusrx.com |
| ID | Term |
|---|---|
| D000795 | Fabry Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D002561 | Cerebrovascular Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C090092 | migalastat |
| C525167 | larazotide acetate |
| C459420 | agalsidase beta |
| C000627036 | agalsidase alfa |
Not provided
Not provided
Not provided
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| Stage 2 |
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| Stage 2 |
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| Period 2: AUC0-t |
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| Period 1: AUCinfinity |
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| Period 2: AUCinfinity |
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Geometric means for each treatment combination is obtained from the linear mixed effects model Log (parameter) = Intercept + ß*Treatment + Error.
| Statistical Analysis of Stage 1 AUCinfinity Data: Point estimates for the geometric means and their 90% CI are obtained by exponentiating the least squares mean and the lower and upper bounds of the 90% CI of the natural log-transformed data. | AUCinfinity Ratio | 2.942 | 2-Sided | 90 | 2.431 | 3.560 | The 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. | Other | Geometric means for each treatment combination is obtained from the linear mixed effects model Log (parameter) = Intercept + ß*Treatment + Error. |
| Statistical Analysis of Stage 2 AUC0-t Data: Point estimates for the geometric means and their 90% CI are obtained by exponentiating the least squares mean and the lower and upper bounds of the 90% CI of the natural log-transformed data. | AUC0-t Ratio | 2.354 | 2-Sided | 90 | 1.826 | 3.035 | The 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. | Other | Geometric means for each treatment combination is obtained from the linear mixed effects model Log (parameter) = Intercept + ß*Treatment + Error. |
| Statistical Analysis of Stage 2 AUCinfinity Data: Point estimates for the geometric means and their 90% CI are obtained by exponentiating the least squares mean and the lower and upper bounds of the 90% CI of the natural log-transformed data. | AUCinfinity Ratio | 2.375 | 2-Sided | 90 | 1.839 | 3.068 | The 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. | Other | Geometric means for each treatment combination is obtained from the linear mixed effects model Log (parameter) = Intercept + ß*Treatment + Error. |
Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
|
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Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
|
|
Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta.
| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
|
|
|
| OG001 | Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
|
|
Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta.
| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
|
|
|
Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta.
| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
|
|
| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
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| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
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| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
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| OG002 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg) | Stage 1: This arm consisted of 3 sequential treatment periods (Period 1 - Period 3). A single 150-mg oral dose (1 capsule) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
| OG003 | Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.5 mg/kg agalsidase beta. |
| OG004 | Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 × 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 1.0 mg/kg agalsidase beta. |
| OG005 | Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg) | Stage 2: This arm consisted of 2 sequential treatment periods (Period 1, Period 2). A single 450-mg oral dose (3 x 150-mg capsules) of migalastat HCl 2 hr before initiation of an IV infusion of 0.2 mg/kg agalsidase alfa. |
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