Safety and Pharmacokinetics of AT1001 (Migalastat HCl) in Healthy Subjects and Subjects With Impaired Renal Function
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)
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
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).
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
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California
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Costa Mesa, California, Forenede Stater, 92626
- GSK Investigational Site
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Florida
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Miami, Florida, Forenede Stater, 33169
- GSK Investigational Site
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Miami, Florida, Forenede Stater, 33014
- GSK Investigational Site
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Orlando, Florida, Forenede Stater, 32809
- GSK Investigational Site
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-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
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Eksperimentel: 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
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AT1001 150mg is available as a capsule
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Number of subjects with adverse events to assess safety and tolerability
Tidsramme: Day 1 to Day 10 (+1)
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Adverse events will be evaluated from Day 1 to the end of study (Day 10 +1).
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Day 1 to Day 10 (+1)
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Clinical laboratory test values to assess safety and tolerability
Tidsramme: Day -28 to Day 10 (+1)
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Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis, Hepatitis A and HIV screen) will be evaluated from screening to the end of the study.
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Day -28 to Day 10 (+1)
|
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Vital signs to assess safety and tolerability
Tidsramme: Day -28 to Day 10 (+1)
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Vital signs (oral temperature, respiratory rate, and seated blood pressure) will be performed from screening to the end of the study.
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Day -28 to Day 10 (+1)
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Physician examination to assess safety and tolerability
Tidsramme: Day -28 to Day 10 (+1)
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Physical examination (general appearance, skin, thorax/lungs, cardiovascular and abdomen) will be performed from screening to the end of the study.
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Day -28 to Day 10 (+1)
|
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Measure of ECG to assess safety and tolerability
Tidsramme: Day -28 to Day 10 (+1)
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Electrocardiogram (ECG) measures the electrical activity of the heart and the hearts' rhythm.
All subjects will undergo ECG testing.
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Day -28 to Day 10 (+1)
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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Maximum observed concentration (Cmax) of AT1001
Tidsramme: Day 1 to Day 6
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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.
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Day 1 to Day 6
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Time to achieve maximum concentration (Tmax) of AT1001
Tidsramme: Day 1 to Day 6
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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.
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Day 1 to Day 6
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Apparent terminal elimination half life (t1/2 ) of AT1001
Tidsramme: Day 1 to Day 6
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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.
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Day 1 to Day 6
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Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001
Tidsramme: Day 1 to Day 6
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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
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Day 1 to Day 6
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Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001
Tidsramme: Day 1 to Day 6
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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
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Day 1 to Day 6
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Apparent terminal elimination rate constant for AT1001
Tidsramme: Day 1 to Day 6
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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
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Day 1 to Day 6
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Oral clearance of AT1001
Tidsramme: Day 1 to Day 6
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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
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Day 1 to Day 6
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Oral volume of distribution of AT1001
Tidsramme: Day 1 to Day 6
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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
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Day 1 to Day 6
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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Hjerte-kar-sygdomme
- Karsygdomme
- Metaboliske sygdomme
- Cerebrovaskulære lidelser
- Hjernesygdomme
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- Nyresygdomme
- Urologiske sygdomme
- Genetiske sygdomme, medfødte
- Genetiske sygdomme, X-forbundet
- Metabolisme, medfødte fejl
- Lysosomale opbevaringssygdomme
- Lipidmetabolismeforstyrrelser
- Hjernesygdomme, metaboliske
- Hjernesygdomme, metaboliske, medfødte
- Sphingolipidoser
- Lysosomale opbevaringssygdomme, nervesystemet
- Cerebrale småkarsygdomme
- Lipidoser
- Lipidmetabolisme, medfødte fejl
- Nyreinsufficiens
- Fabrys sygdom
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- 116431
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