Safety and Pharmacokinetics of AT1001 (Migalastat HCl) in Healthy Subjects and Subjects With Impaired Renal Function

Fabry Disease Clinical Trial

Official title:

An Open-Label Study to Determine the Safety and Pharmacokinetics of AT1001 in Subjects With Impaired Renal Function and Healthy Subjects With Normal Renal Function (AT1001-015)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01730469
• Other study ID #: 116431
• Status: Completed
• Phase: Phase 1
• First received: November 8, 2012
• Last updated: August 2, 2017
• Start date: August 2011
• Est. completion date: April 2012

Study information

• Verified date: August 2017
• Source: Amicus Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety, tolerability, and pharmacokinetics (PK) study of a single dose of 150 mg AT1001 (migalastat HCl, GR181413A) administered orally to healthy subjects with normal renal function and to subjects with mild, moderate, and severe renal impairment.

Description:

This will be an open-label, non-randomized, multiple-center, sequential group, safety, tolerability, and PK study of a single dose of AT1001 (migalastat HCl, GR181413A) administered orally as a 150 mg dose in fasted healthy control male and female subjects with normal renal function compared to mild, moderate, and severe renally-impaired subjects (classified by level of creatinine clearance [CLcr] as determined by the Cockcroft-Gault formula).

Screening will occur from Day -28 to Day -2. Subjects will check-in to the clinic on Day -1 and receive a single oral dose of 150 mg AT1001 on Day 1. Subjects will be discharged from the clinic on Day 2 (if stable as determined by the Investigator) and return for daily visits on Day 3 through Day 6 for a safety assessment and PK sampling. Subjects will undergo a follow-up visit on Day 7 (+1) and an end of study visit on Day 10 (+1).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria All subjects

• males or females aged 18 to 70 years inclusive (subjects with normal renal function, mild or moderate renal impairment), and 18 to 75 years inclusive (subjects with severe renal impairment)

• body mass index 18.0 to 40.0 kilogram (kg)/square meter (m^2) inclusive

• females who are non-pregnant, non-lactating, or postmenopausal for >=1 year, surgically sterile for >= 90 days, or agree to use approved methods of contraception

• males will be sterile or use approved methods of contraception

• understands and signs informed consent form Healthy subjects with normal renal function

• negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in

• good health with no clinically significant medical history, physical examination, vital signs, or 12-lead ECG

• clinical laboratory tests within the reference range or not clinically significant

• normal renal function (estimated CLcr >90 mL/min) at Screening Subjects with mild, moderate or severe renal impairment

• negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in or verification of a prescription for a positive test

• renal impairment (estimated CLcr <90 mL/min)

• evidence of stable renal impairment defined as two separate estimated CLcr values within 25%

• clinical laboratory results consistent with their renal condition or of no clinical significance for the study

• abnormal laboratory values must not be clinically significant. Anemia secondary to renal disease is acceptable if hemoglobin is =9 g/dL and no clinically significant symptoms. Liver enzymes and bilirubin must be below twice the upper normal level

• subjects with renal impairment must have stable underlying medical conditions < 90 days before study start

• stable medication regimen(s) (no new drug(s) or changed dosage(s) <30 days before study drug)

• in good general health, allowing for concurrent illnesses associated with chronic kidney disease

Exclusion Criteria:

All subjects:

• history of hypersensitivity or allergies to any drug, unless approved by the Investigator and reviewed by Sponsor/Medical Monitor

• participation in a study with receipt of an investigational drug < 5 half-lives or 30 days (whichever is longer) before Check-in

• use of alcohol, grapefruit, or caffeine-containing foods or beverages < 72 hours before Check-in, unless approved by the Investigator and reviewed by the Sponsor/Medical Monitor

• poor peripheral venous access

• whole blood donation < 56 days before dosing or plasma donation < 14 days before dosing

• receipt of blood products < 2 months before Check-in

• history or presence of any clinically significant abnormal ECG

• history of alcoholism or drug addiction < 1 year before Check-in

• positive test for HIV antibody, HBsAg or anti-HCV

• pregnant or breastfeeding

Healthy subjects with normal renal function:

• use of any tobacco- or nicotine-containing products < 6 months before Check-in

• clinically significant (history of or active) cardiac, hepatic, pulmonary, endocrine, neurological, infectious, gastrointestinal, hematologic, oncologic, or psychiatric disease putting the subject at increased risk or could interfere with study objectives

• screening laboratory values outside normal range and deemed clinically significant by the Investigator

• use of a prescription drug < 14 days of dosing or a non-prescription drug < 7 days before dosing or need of concomitant medication during the study

Subjects with mild, moderate, or severe renal impairment:

• unstable disease (concurrent medical conditions that have changed significantly < 90 days)

• changes in concomitant prescription medications < 30 days before dosing or expected changes during study

• use of new non-prescription medication < 30 days before dosing

• renal transplant

• acute or chronic non-renal condition limiting the subject's ability to complete and/or participate in the study

Related Conditions & MeSH terms

• Fabry Disease
• Renal Insufficiency

Intervention

Drug:
• AT1001 150 mg
AT1001 150mg is available as a capsule

Locations

Country	Name	City	State
United States	GSK Investigational Site	Costa Mesa	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Amicus Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events to assess safety and tolerability	Adverse events will be evaluated from Day 1 to the end of study (Day 10 +1).	Day 1 to Day 10 (+1)
Primary	Clinical laboratory test values to assess safety and tolerability	Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis, Hepatitis A and HIV screen) will be evaluated from screening to the end of the study.	Day -28 to Day 10 (+1)
Primary	Vital signs to assess safety and tolerability	Vital signs (oral temperature, respiratory rate, and seated blood pressure) will be performed from screening to the end of the study.	Day -28 to Day 10 (+1)
Primary	Physician examination to assess safety and tolerability	Physical examination (general appearance, skin, thorax/lungs, cardiovascular and abdomen) will be performed from screening to the end of the study.	Day -28 to Day 10 (+1)
Primary	Measure of ECG to assess safety and tolerability	Electrocardiogram (ECG) measures the electrical activity of the heart and the hearts' rhythm. All subjects will undergo ECG testing.	Day -28 to Day 10 (+1)
Secondary	Maximum observed concentration (Cmax) of AT1001	Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the resultant maximum plasma concentration (Cmax) will be measured in subjects with impaired renal function and normal renal function.	Day 1 to Day 6
Secondary	Time to achieve maximum concentration (Tmax) of AT1001	Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and time to maximum concentration (tmax) will be measured in subjects with impaired renal function and normal renal function.	Day 1 to Day 6
Secondary	Apparent terminal elimination half life (t1/2 ) of AT1001	Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and and apparent terminal elimination half-life (t1/2) will be measured in subjects with impaired renal function and normal renal function.	Day 1 to Day 6
Secondary	Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001	Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-t will be measured in subjects with impaired renal function and normal renal function	Day 1 to Day 6
Secondary	Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001	Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-inf will be measured in subjects with impaired renal function and normal renal function	Day 1 to Day 6
Secondary	Apparent terminal elimination rate constant for AT1001	Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the apparent terminal elimination rate constant will be measured in subjects with impaired renal function and normal renal function	Day 1 to Day 6
Secondary	Oral clearance of AT1001	Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral clearance will be measured in subjects with impaired renal function and normal renal function	Day 1 to Day 6
Secondary	Oral volume of distribution of AT1001	Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral volume of distribution will be measured in subjects with impaired renal function and normal renal function	Day 1 to Day 6