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Fabry DiseasePhase 2NCT01196871

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

A Phase 2 study testing Migalastat HCl, Agalsidase Beta and Agalsidase Alfa in people with Fabry Disease, run by Amicus Therapeutics at 10 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 more about this study

Who is it for?
Ages 18 to 65 years, men only
Conditions the study is for
Fabry Disease
What is being tested?
Migalastat HCl, Agalsidase Beta and Agalsidase Alfa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
10 sitesin 5 countries
Study dates
2 Feb 2011to 9 Oct 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

10 sites in 5 countries.

10 sites in 5 countries

United States5 sites
  • Study site

    Birmingham, Alabama, 35294

  • Study site

    Decatur, Georgia, 30033

  • Study site

    Iowa City, Iowa, 52242

  • Study site

    Kansas City, Kansas, 66160

  • Study site

    Springfield, Virginia, 22152

Other trials in United States

Australia2 sites
  • Study site

    Nedlands

  • Study site

    Parkville

Other trials in Australia

Belgium1 site
  • Study site

    Edegem

Other trials in Belgium

Canada1 site
  • Study site

    Montreal

Other trials in Canada

Netherlands1 site
  • Study site

    Amsterdam

Other trials in Netherlands

About this study

Official title: An Open-label Phase 2A Study to Investigate Drug-Drug Interactions Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Subjects With Fabry Disease

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.

Conditions
Fabry Disease
Being tested
Migalastat HCl, Agalsidase Beta, Agalsidase Alfa
Keywords
Amicus Therapeutics, AT1001, Galafold, Migalastat, Pharmacokinetics
Medical subject headings
Fabry Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Migalastat HClDrug

    Also called AT1001, Galafold, migalastat

    Oral capsules, single dose

  • Agalsidase BetaBiological

    Also called Fabrazyme

    IV infusion, single dose

  • Agalsidase AlfaBiological

    Also called Replagal

    IV infusion, single dose

Study groups in NCT01196871
Study groupRoleWhat they receive
Agalsidase Beta (0.5 mg/kg)-Migalastat (150 mg)ExperimentalNot described
Receives: Drug: Migalastat HCl; Biological: Agalsidase Beta
Agalsidase Beta (1.0 mg/kg)-Migalastat (150 mg)ExperimentalNot described
Receives: Drug: Migalastat HCl; Biological: Agalsidase Beta
Agalsidase Alfa (0.2 mg/kg)-Migalastat (150 mg)ExperimentalNot described
Receives: Drug: Migalastat HCl; Biological: Agalsidase Alfa
Agalsidase Beta (0.5 mg/kg)-Migalastat (450 mg)ExperimentalNot described
Receives: Drug: Migalastat HCl; Biological: Agalsidase Beta
Agalsidase Beta (1.0 mg/kg)-Migalastat (450 mg)ExperimentalNot described
Receives: Drug: Migalastat HCl; Biological: Agalsidase Beta
Agalsidase Alfa (0.2 mg/kg)-Migalastat (450 mg)ExperimentalNot described
Receives: Drug: Migalastat HCl; Biological: Agalsidase Alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 0 hr, 1 day post dose

Secondary outcomes (1)
  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.

    Measured: Baseline, Day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2010 (estimated)
  2. Study start2 Feb 2011
  3. Primary completion9 Oct 2012
  4. Study completion9 Oct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
A 2-stage design was used to study the effects of 2 dose levels of migalastat, while a 2- or 3-period design within each stage enabled study of the effects of one drug on the PK, pharmacodynamics, and safety of the other drug.
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01196871
Sponsor's protocol ID
AT1001-013
Status last verified
Nov 2018
First submitted
7 Sep 2010
Last updated
19 Dec 2018
Data monitoring committee
Yes

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Migalastat HCl, Agalsidase Beta and Agalsidase Alfa in people with Fabry Disease, run by Amicus Therapeutics at 10 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Australia, Belgium, Canada, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change In Area Under The Plasma Concentration Versus Time Curve (AUC) For Active α-Galactosidase A (α-Gal A) Levels After Administration Of Migalastat (time frame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01196871, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2018.

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