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

NCT01730469 | Completed Phase 1

• 1 other identifier: 116431
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Fabry Disease

Keywords

Pharmacokinetics; GR181413; Safety; AT1001; Migalastat hydrochloride

Outcome Measures

Primary Outcomes (5)

• 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)

• 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)

• 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)

• 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)

• 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 Outcomes (8)

• Maximum observed concentration (Cmax) of AT1001

  Day 1 to Day 6

• Time to achieve maximum concentration (Tmax) of AT1001

  Day 1 to Day 6

• Apparent terminal elimination half life (t1/2 ) of AT1001

  Day 1 to Day 6

• Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001

  Day 1 to Day 6

• Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001

  Day 1 to Day 6

Study Arms (1)

AT1001 150 mg

EXPERIMENTAL

Each subject will receive a single oral dose of AT1001 150 mg administered orally with 240 mL room temperature water after at least a 4-hour fast

Drug: AT1001 150 mg

Interventions

AT1001 150 mg DRUG

AT1001 150mg is available as a capsule

Also known as: migalastat HCl, GR181413A

AT1001 150 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amicus Therapeutics: lead

Study Sites (4)

GSK Investigational Site

Costa Mesa, California, 92626, United States

Location

GSK Investigational Site

Miami, Florida, 33014, United States

Location

GSK Investigational Site

Miami, Florida, 33169, United States

Location

GSK Investigational Site

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• Johnson FK, Mudd PN Jr, DiMino T, Vosk J, Sitaraman S, Boudes P, France N, Barlow C. An open-label study to determine the pharmacokinetics and safety of migalastat HCl in subjects with impaired renal function and healthy subjects with normal renal function. Clin Pharmacol Drug Dev. 2015 Jul;4(4):256-61. doi: 10.1002/cpdd.149. Epub 2014 Dec 22.

  PMID: 27136905 DERIVED

MeSH Terms

Conditions

Fabry Disease

Interventions

larazotide acetate; migalastat

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Medical Monitor, Clinical Research

  Amicus Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2012
• First Posted: November 21, 2012
• Study Start: August 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: August 3, 2017

Record last verified: 2017-08

Locations

US (4)