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

2 augusti 2017 uppdaterad av: Amicus Therapeutics

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)

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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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).

Studietyp

Interventionell

Inskrivning (Faktisk)

32

Fas

  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

    • California
      • Costa Mesa, California, Förenta staterna, 92626
        • GSK Investigational Site
    • Florida
      • Miami, Florida, Förenta staterna, 33169
        • GSK Investigational Site
      • Miami, Florida, Förenta staterna, 33014
        • GSK Investigational Site
      • Orlando, Florida, Förenta staterna, 32809
        • GSK Investigational Site

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 75 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Ja

Kön som är behöriga för studier

Allt

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: AT1001 150 mg
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
AT1001 150mg is available as a capsule
Andra namn:
  • migalastat HCl
  • GR181413A

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Number of subjects with adverse events to assess safety and tolerability
Tidsram: Day 1 to Day 10 (+1)
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
Tidsram: Day -28 to Day 10 (+1)
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
Tidsram: Day -28 to Day 10 (+1)
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
Tidsram: Day -28 to Day 10 (+1)
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
Tidsram: Day -28 to Day 10 (+1)
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)

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Maximum observed concentration (Cmax) of AT1001
Tidsram: Day 1 to Day 6
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
Time to achieve maximum concentration (Tmax) of AT1001
Tidsram: Day 1 to Day 6
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
Apparent terminal elimination half life (t1/2 ) of AT1001
Tidsram: Day 1 to Day 6
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
Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001
Tidsram: Day 1 to Day 6
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
Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001
Tidsram: Day 1 to Day 6
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
Apparent terminal elimination rate constant for AT1001
Tidsram: Day 1 to Day 6
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
Oral clearance of AT1001
Tidsram: Day 1 to Day 6
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
Oral volume of distribution of AT1001
Tidsram: Day 1 to Day 6
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

Samarbetspartners och utredare

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Publikationer och användbara länkar

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Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 augusti 2011

Primärt slutförande (Faktisk)

1 april 2012

Avslutad studie (Faktisk)

1 april 2012

Studieregistreringsdatum

Först inskickad

8 november 2012

Först inskickad som uppfyllde QC-kriterierna

15 november 2012

Första postat (Uppskatta)

21 november 2012

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

3 augusti 2017

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

2 augusti 2017

Senast verifierad

1 augusti 2017

Mer information

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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