Clinical trial NCT01196871: Drug-Drug Interaction Study Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Participants With Fabry Disease
Official title: An Open-label Phase 2A Study to Investigate Drug-Drug Interactions Between AT1001 (Migalastat Hydrochloride) and Agalsidase in Subjects With Fabry Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fabry Disease
Keywords: Amicus Therapeutics
AT1001
Galafold
Migalastat
Pharmacokinetics
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2010-09-09
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: The objective was to determine the effects of a single dose of migalastat hydrochloride (HCl) (migalastat) 150 and 450 milligrams (mg) on the safety and plasma pharmacokinetics (PK) of agalsidase and the effects of agalsidase on the safety and PK of migalastat 150 mg.

Detailed description: This open-label study was conducted in 2 stages (Stage 1, Stage 2). Stage 1 included migalastat 150 mg; Stage 2 included migalastat 450 mg. Each dose of migalastat was selected to evaluate interaction with each of 3 doses of recombinant agalsidase: 0.5 mg/kilogram (kg) agalsidase beta; 1.0 mg/kg agalsidase beta; 0.2 mg/kg agalsidase alfa.

Migalastat was administered orally. Agalsidase alfa was administered as a 40-minute intravenous (IV) infusion and agalsidase beta was administered as a 2-hour (hr) IV infusion.

Stage 1 consisted of 3 treatment periods with 14 days intervening between each period.

Period 1, Day 1: agalsidase was administered alone.

Period 2, Day 1: migalastat was administered, followed 2 hrs later by agalsidase.

Period 3, Day 7: migalastat was administered alone.

Stage 2 consisted of two 14-day treatment periods in which the plasma exposure of migalastat was characterized when migalastat was administered with agalsidase solely to confirm the attainment of adequate migalastat plasma concentrations.

Period 1, Day 1: agalsidase was administered as an IV infusion using a calibrated infusion pump.

Period 2, Day 1: migalastat was administered, followed 2 hrs later by agalsidase.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
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
timeFrame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose
measure: Change In Maximum Observed Plasma Concentration (Cmax) For Active α-Gal A Levels After Administration Of Migalastat
timeFrame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose
measure: 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
timeFrame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose
measure: Change In AUC For Total α-Gal A Protein Levels After Administration Of Migalastat
timeFrame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose
measure: 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
timeFrame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose
measure: Change In Cmax For Total α-Gal A Protein Levels After Administration Of Migalastat
timeFrame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose
measure: Change In Tmax And T1/2 For Total α-Gal A Protein Levels After Administration Of Migalastat
timeFrame: 0 hr, 2 hr, 2 days, 7 days, 14 days post dose
measure: Change In AUC For Migalastat After Administration Of Agalsidase
timeFrame: 0 hr, 1 day post dose
measure: Change In Cmax For Migalastat After Administration Of Agalsidase
timeFrame: 0 hr, 1 day post dose
measure: Change In Tmax And T1/2 For Migalastat After Administration Of Agalsidase
timeFrame: 0 hr, 1 day post dose
Secondary outcomes:
measure: Change From Baseline To Day 7 In Active α-Gal A In Skin Following Treatment With Agalsidase Alone And Co-administration With Migalastat
timeFrame: Baseline, Day 7
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Decatur
country: United States
state: Georgia
city: Iowa City
country: United States
state: Iowa
city: Kansas City
country: United States
state: Kansas
city: Springfield
country: United States
state: Virginia
city: Nedlands
country: Australia
city: Parkville
country: Australia
city: Edegem
country: Belgium
city: Montreal
country: Canada
city: Amsterdam
country: Netherlands
Study officials:
affiliation: Amicus Therapeutics
name: Medical Monitor Clinical Research
role: STUDY_DIRECTOR
References:
citation: Warnock DG, Bichet DG, Holida M, Goker-Alpan O, Nicholls K, Thomas M, Eyskens F, Shankar S, Adera M, Sitaraman S, Khanna R, Flanagan JJ, Wustman BA, Barth J, Barlow C, Valenzano KJ, Lockhart DJ, Boudes P, Johnson FK. Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active alpha-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase. PLoS One. 2015 Aug 7;10(8):e0134341. doi: 10.1371/journal.pone.0134341. eCollection 2015.