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

NCT ID: NCT01196871

Last Updated: 2018-12-19

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-02

Study Completion Date

2012-10-09

Brief Summary

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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.

Detailed Description

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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

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Fabry Disease

Keywords

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Amicus Therapeutics AT1001 Galafold Migalastat Pharmacokinetics

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

Group Type EXPERIMENTAL

Migalastat HCl

Intervention Type DRUG

Oral capsules, single dose

Agalsidase Beta

Intervention Type BIOLOGICAL

IV infusion, single dose

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

Group Type EXPERIMENTAL

Migalastat HCl

Intervention Type DRUG

Oral capsules, single dose

Agalsidase Beta

Intervention Type BIOLOGICAL

IV infusion, single dose

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

Group Type EXPERIMENTAL

Migalastat HCl

Intervention Type DRUG

Oral capsules, single dose

Agalsidase Alfa

Intervention Type BIOLOGICAL

IV infusion, single dose

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

Group Type EXPERIMENTAL

Migalastat HCl

Intervention Type DRUG

Oral capsules, single dose

Agalsidase Beta

Intervention Type BIOLOGICAL

IV infusion, single dose

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

Group Type EXPERIMENTAL

Migalastat HCl

Intervention Type DRUG

Oral capsules, single dose

Agalsidase Beta

Intervention Type BIOLOGICAL

IV infusion, single dose

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

Group Type EXPERIMENTAL

Migalastat HCl

Intervention Type DRUG

Oral capsules, single dose

Agalsidase Alfa

Intervention Type BIOLOGICAL

IV infusion, single dose

Interventions

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Migalastat HCl

Oral capsules, single dose

Intervention Type DRUG

Agalsidase Beta

IV infusion, single dose

Intervention Type BIOLOGICAL

Agalsidase Alfa

IV infusion, single dose

Intervention Type BIOLOGICAL

Other Intervention Names

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AT1001 Galafold migalastat Fabrazyme Replagal

Eligibility Criteria

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Inclusion Criteria

* Male diagnosed with Fabry disease and between 18 and 65 years of age, inclusive
* Body mass index between 18-35 kg per meter squared
* Had initiated treatment with agalsidase at least 1 month prior to screening, and had received at least 2 infusions before screening
* Had stable dose level, dosing regimen, and form of agalsidase for at least 1 month before screening
* Had an estimated creatinine clearance greater than or equal to 50 milliliters (mL)/minute at screening
* Agreed to use medically accepted methods of contraception during the study and for 30 days after study completion
* Were willing and able to provide written informed consent

Exclusion Criteria

* Had a documented transient ischemic attack, ischemic stroke, unstable angina, or myocardial infarction within the 3 months before screening
* Had clinically significant unstable cardiac disease (for example, cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or New York Heart Association class III or IV congestive heart failure)
* History of allergy or sensitivity to study drug (including excipients) or other iminosugars (such as miglustat, miglitol)
* Required a concomitant medication prohibited by the protocol: Glyset® (miglitol), or Zavesca® (miglustat)
* Any investigational/experimental drug or device within 30 days of screening, except for use of investigational enzyme replacement therapy for Fabry disease
* Had any intercurrent illness or condition that might have precluded the participant from fulfilling the protocol requirements or suggested to the investigator that the potential participant might have had an unacceptable risk by participating in this study
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Amicus Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor Clinical Research

Role: STUDY_DIRECTOR

Amicus Therapeutics

Locations

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Birmingham, Alabama, United States

Site Status

Decatur, Georgia, United States

Site Status

Iowa City, Iowa, United States

Site Status

Kansas City, Kansas, United States

Site Status

Springfield, Virginia, United States

Site Status

Nedlands, , Australia

Site Status

Parkville, , Australia

Site Status

Edegem, , Belgium

Site Status

Montreal, , Canada

Site Status

Amsterdam, , Netherlands

Site Status

Countries

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France United Kingdom United States Australia Belgium Canada Netherlands

References

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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.

Reference Type RESULT
PMID: 26252393 (View on PubMed)

Other Identifiers

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AT1001-013

Identifier Type: -

Identifier Source: org_study_id