Migalastat Food Effect Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Fabry Disease

Intervention / Treatment
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* Drug: A (migalastat)
* Drug: B (migalastat)
* Drug: C (migalastat)
* Drug: D (migalastat)
* Drug: E (migalastat)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  | 5 weeks | 
| Clinical Laboratory Tests |  | 5 weeks | 
| Vital Signs |  | 5 weeks | 
| ECGs |  | 5 weeks | 
| Physical Examination |  | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food effect, GR181413A, AT1001, migalastat hydrochloride, Lysosomal storage disorders, Pharmacokinetics