Migalastat Food Effect Study

A Randomized, Open-Label, 5-Period Crossover Study to Evaluate the Effect of Meal Type and Timing on the Pharmacokinetics of Migalastat Hydrochloride in Healthy Volunteers.

A 5-period crossover study to evaluate the effect of meal type and timing on migalastat HCl pharmacokinetics in healthy male and female subjects. Subjects will be randomly assigned to 1 of 5 treatment sequences and will receive each treatment over the course of 5 weekly periods.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: A (migalastat); Drug: B (migalastat); Drug: C (migalastat); Drug: D (migalastat); Drug: E (migalastat)

Detailed Description

This is a Phase 1, randomized, open-label, 5-period crossover study to evaluate the effect of meal type and timing on migalastat HCl pharmacokinetics in healthy male and female subjects between the ages of 18 and 65 years. A total of 20 subjects will be enrolled such that approximately 14 evaluable subjects complete dosing and critical assessments. Subjects will be randomly assigned to 1 of 5 treatment sequences and will receive each treatment over the course of 5 successive weekly periods including a single dose of migalastat HCl 150 mg in the fasting state as the reference treatment. There will be at least a 7-day washout period between each dose of migalastat HCl and a follow-up visit approximately 7 to 10 days after the last dose in Period 5.

All subjects will be screened within 28 days of admission to the clinical unit. In each period, subjects will check in to the clinical unit the day prior to drug administration and have relevant assessments to ensure continued eligibility for dose administration. On Day 1 of each period, subjects will receive a single dose of migalastat HCl within 1 of the following 5 treatment regimens as follows:

• 150 mg migalastat HCl in the fasting state (reference arm)
• 150 mg migalastat HCl with simultaneous consumption of a glucose drink
• 150 mg migalastat HCl 1 hour before consumption of a high fat meal
• 150 mg migalastat HCl 1 hour before consumption of a light meal
• 150 mg migalastat HCl 1 hour after consumption of a light meal

Subjects will be confined to the clinical unit for 24 hours after dosing with serial blood samples collected for PK analysis. Safety will be assessed throughout the study by monitoring clinical laboratory tests, ECGs, physical examinations, vital signs, and AEs.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female aged 18 to 65 years inclusive
• Healthy, as determined by study physician
• Capable of giving informed consent

Exclusion Criteria:

• Positive for HIV or Hepatitis B and/or C viruses
• History of drug or alcohol abuse or addiction within 2 years
• Smoker or consumes tobacco products
• Participation in a clinical trial within 30 days of scheduled first dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Reference; Fasted	Drug: A (migalastat); 150 mg migalastat HCl in the fasting state (reference arm)
EXPERIMENTAL: Glucose Drink; Fed	Drug: B (migalastat); 150 mg migalastat HCl with simultaneous consumption of a glucose drink
EXPERIMENTAL: Before High Fat Meal; Fed	Drug: C (migalastat); 150 mg migalastat HCl 1 hour before consumption of a high fat meal
EXPERIMENTAL: Before Light Meal; Fed	Drug: D (migalastat); 150 mg migalastat HCl 1 hour before consumption of a light meal
EXPERIMENTAL: After Light Meal; Fed	Drug: E (migalastat); 150 mg migalastat HCl 1 hour after consumption of a light meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration of migalastat HCl after a single dose	Cmax	5 weeks (60 PK timepoints)
Time of occurence of maximum observed plasma concentration of migalastat HCl after a single dose	tmax	5 weeks (60 PK timepoints)
Area under the plasma concentration-time curve of migalastat HCl after a single dose from time 0 (before dosing) to infinity	AUC (0 to infinity)	5 weeks (60 PK timepoints)
Terminal phase half life of migalastat HCl after a single dose	t1/2	5 weeks (60 PK timepoints)
Apparent clearance following oral dosing of migalastat HCl after a single dose	CL/F	5 weeks (60 PK timepoints)
Area under the plasma concentration-time curve of migalastat HCl after a single dose from time 0 (before dosing) to the time of the last quantifiable concentration	AUC (0 to t)	5 weeks (60 PK timepoints)

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse Events	5 weeks
Clinical Laboratory Tests	5 weeks
Vital Signs	5 weeks
ECGs	5 weeks
Physical Examination	5 weeks

Collaborators and Investigators

• Sponsor: Amicus Therapeutics
• Investigators: Study Director: Medical Monitor, Clinical Research, AmicusTherapeutics

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: October 20, 2011
• First Submitted That Met QC Criteria: December 8, 2011
• First Posted (ESTIMATE): December 12, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): December 18, 2013
• Last Update Submitted That Met QC Criteria: December 17, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Food effect; AT1001; Lysosomal storage disorders; migalastat hydrochloride; GR181413A
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; 1-Deoxynojirimycin
• Other Study ID Numbers: 116050