Clinical trial NCT01730469: Safety and Pharmacokinetics of AT1001 (Migalastat HCl) in Healthy Subjects and Subjects With Impaired Renal Function
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fabry Disease
Keywords: Pharmacokinetics
GR181413
Safety
AT1001
Migalastat hydrochloride
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2012-11-21
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with adverse events to assess safety and tolerability
timeFrame: Day 1 to Day 10 (+1)
measure: Clinical laboratory test values to assess safety and tolerability
timeFrame: Day -28 to Day 10 (+1)
measure: Vital signs to assess safety and tolerability
timeFrame: Day -28 to Day 10 (+1)
measure: Physician examination to assess safety and tolerability
timeFrame: Day -28 to Day 10 (+1)
measure: Measure of ECG to assess safety and tolerability
timeFrame: Day -28 to Day 10 (+1)
Secondary outcomes:
measure: Maximum observed concentration (Cmax) of AT1001
timeFrame: Day 1 to Day 6
measure: Time to achieve maximum concentration (Tmax) of AT1001
timeFrame: Day 1 to Day 6
measure: Apparent terminal elimination half life (t1/2 ) of AT1001
timeFrame: Day 1 to Day 6
measure: Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001
timeFrame: Day 1 to Day 6
measure: Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001
timeFrame: Day 1 to Day 6
measure: Apparent terminal elimination rate constant for AT1001
timeFrame: Day 1 to Day 6
measure: Oral clearance of AT1001
timeFrame: Day 1 to Day 6
measure: Oral volume of distribution of AT1001
timeFrame: Day 1 to Day 6
Other outcomes:
Locations:
city: Costa Mesa
country: United States
facility: GSK Investigational Site
state: California
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
Study officials:
affiliation: Amicus Therapeutics
name: Medical Monitor, Clinical Research
role: STUDY_DIRECTOR
References:
citation: 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.