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

2 augustus 2017 bijgewerkt door: 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.

Studie Overzicht

Toestand

Voltooid

Interventie / Behandeling

Gedetailleerde beschrijving

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).

Studietype

Ingrijpend

Inschrijving (Werkelijk)

32

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

    • California
      • Costa Mesa, California, Verenigde Staten, 92626
        • GSK Investigational Site
    • Florida
      • Miami, Florida, Verenigde Staten, 33169
        • GSK Investigational Site
      • Miami, Florida, Verenigde Staten, 33014
        • GSK Investigational Site
      • Orlando, Florida, Verenigde Staten, 32809
        • GSK Investigational Site

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 75 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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
Andere namen:
  • migalastat HCl
  • GR181413A

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of subjects with adverse events to assess safety and tolerability
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Maximum observed concentration (Cmax) of AT1001
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 augustus 2011

Primaire voltooiing (Werkelijk)

1 april 2012

Studie voltooiing (Werkelijk)

1 april 2012

Studieregistratiedata

Eerst ingediend

8 november 2012

Eerst ingediend dat voldeed aan de QC-criteria

15 november 2012

Eerst geplaatst (Schatting)

21 november 2012

Updates van studierecords

Laatste update geplaatst (Werkelijk)

3 augustus 2017

Laatste update ingediend die voldeed aan QC-criteria

2 augustus 2017

Laatst geverifieerd

1 augustus 2017

Meer informatie

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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