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A Phase I Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144

20. august 2026 oppdatert av: AstraZeneca

A Phase I, Multicentre, Single-Dose, Non-Randomised, Open-Label, Parallel-Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144

This Phase I, open-label, parallel group study will investigate the single oral dose PK, safety, and tolerability of AZD4144 to male and female participants with mild, moderate, and severe hepatic impairment compared to matched controls with normal hepatic function.

Studieoversikt

Status

Har ikke rekruttert ennå

Intervensjon / Behandling

Detaljert beskrivelse

This Phase I, open-label, parallel group study will investigate the single oral dose PK, safety, and tolerability of AZD4144 to male and female participants with mild, moderate, and severe hepatic impairment compared to matched controls with normal hepatic function.

Approximately 60 participants are planned to be screened to achieve up to 30 evaluable participants. For each of the 3 hepatic impairment groups, 6 participants are planned to complete the study. Initially, 6 participants with normal hepatic function will be recruited, matched on a group level regarding sex, age, and BMI to the participants with hepatic impairment. Additional participants with normal hepatic function, up to a total of 12, may be included if needed to meet the matching criteria.

Studietype

Intervensjonell

Registrering (Antatt)

30

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

    • Arizona
      • Mesa, Arizona, Forente stater, 85210
        • Research Site
    • Florida
      • Miami Lakes, Florida, Forente stater, 33014
        • Research Site
      • Orlando, Florida, Forente stater, 32809
        • Research Site
    • Texas
      • Austin, Texas, Forente stater, 78757
        • Research Site

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Ja

Beskrivelse

Inclusion Criteria:

Healthy Matched Control Participants Only (Group 4):

• Must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1.

Hepatically-Impaired Participants Only (Groups 1, 2, and 3):

  • Must have a diagnosis of chronic (≥ 6 months) and stable hepatic impairment (e.g., no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status within 30 days prior to study screening, as determined by the investigator at screening and Day -1).
  • Must be classified by the investigator as CP Class A (Group 1), CP Class B (Group 2), or CP Class C (Group 3) at screening.
  • Participant must be stable on a concomitant medication and/or treatment regimen (defined as not starting a new treatment/medication[s] or a change in the dosage or frequency of the concomitant medication[s] within at least 2 weeks prior to screening).

All Groups:

  • Body weight ≥ 50 kg and body mass index (BMI) within the range 18 to 45 kg/m2, inclusive.
  • All Females of Childbearing Potential (FOCBP) must have a negative pregnancy test at screening and Day -1.

Exclusion Criteria:

  • History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
  • Have Type 1 diabetes mellitus or T2DM (Group 4)
  • Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.
  • History of long QT syndrome or prolonged QTcF.
  • Presence of unstable medical or psychological conditions, or any evidence of additional severe or uncontrolled systemic disease (e.g., currently unstable or uncompensated renal, cardiovascular, or respiratory disease).
  • Evidence of renal impairment at screening
  • Current liver transplant or anticipated to receive liver transplant within 2 months of screening or Day -1 (Group 1, 2 and 3).
  • Use of any of the prescription and non-prescription prohibited medications.
  • Concomitant immunosuppressive, steroid treatment.
  • Live or attenuated vaccines within 3 months prior to study intervention or live vaccinations planned during the trial.
  • History of severe allergy/hypersensitivity of AZD4144 or any of the excipients of the product.
  • Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days prior to study intervention in this study or, if known, 5 half-lives from last dose in the previous study to study intervention in this study, whichever is longest.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Gruppe 1
Deltakere med lett nedsatt leverfunksjon (CP klasse A, score på 5 eller 6)
Single oral dose of AZD4144 in participants from all groups
Eksperimentell: Gruppe 2
Participants with moderate hepatic impairment (CP Class B, score of 7 to 9).
Single oral dose of AZD4144 in participants from all groups
Eksperimentell: Group 3
Participants with severe hepatic impairment (CP Class C, score of 10 to 15).
Single oral dose of AZD4144 in participants from all groups
Eksperimentell: Group 4
Participants with normal hepatic function matched on a group level regarding sex, age, and BMI to the impaired groups
Single oral dose of AZD4144 in participants from all groups

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
PK parameters AUCinf
Tidsramme: Day 0 through Day 7 or 9
area under the concentration-time curve from zero to infinity
Day 0 through Day 7 or 9
PK parameter AUClast
Tidsramme: Day 0 through Day 7 or 9
area under the concentration-time curve from zero to the last measurable concentration
Day 0 through Day 7 or 9
PK parameters AUC(0-144)
Tidsramme: Day 0 through Day 7
area under the curve from time zero to time 144hours post dose
Day 0 through Day 7
PK parameter Cmax
Tidsramme: Day 0 through Day 7 or 9
maximum observed plasma concentration
Day 0 through Day 7 or 9

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
PK parameters tmax
Tidsramme: Day 0 through Day 7 or 9
time to reach maximum observed plasma concentration
Day 0 through Day 7 or 9
PK Parameters t1/2λz
Tidsramme: Day 0 through Day 7 or 9
half-life associated with terminal slope (λz)
Day 0 through Day 7 or 9
PK Parameters CL/F
Tidsramme: Day 0 through Day 7 or 9
apparent total body clearance of drug from plasma after extravascular administration
Day 0 through Day 7 or 9
PK Parameters Vz/F
Tidsramme: Day 0 through Day 7 or 9
apparent volume of distribution during the terminal phase after extravascular administration.
Day 0 through Day 7 or 9
PK Parameters CLNR/F
Tidsramme: Day 0 through Day 7 or 9
non-renal clearance of drug from plasma
Day 0 through Day 7 or 9
PK parameters CLR from urine concentrations
Tidsramme: Day 0 through Day 3
renal clearance from urine concentration
Day 0 through Day 3
PK parameters Ae determined from urine concentration
Tidsramme: Day 0 through Day 3
amount of unchanged drug excreted into the urine
Day 0 through Day 3
PK parameters fe determined from urine concentration
Tidsramme: Day 0 through Day 3
Percentage of unchanged drug excreted into the urine
Day 0 through Day 3
PK Parameters tlast
Tidsramme: Day 0 through Day 7 or 9
time of last quantifiable concentration
Day 0 through Day 7 or 9
PK Parameters λz
Tidsramme: Day 0 through Day 7 or 9
terminal elimination rate constant
Day 0 through Day 7 or 9
PK Parameters AUC(0-24)
Tidsramme: Day 0 through Day 1
area under the plasma concentration-time curve from time 0 to 24 hours postdose
Day 0 through Day 1
PK Parameters AUC(0-72)
Tidsramme: Day 0 through Day 3
area under the plasma concentration-time curve from time 0 to 72 hours postdose
Day 0 through Day 3

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

24. august 2026

Primær fullføring (Antatt)

28. mai 2027

Studiet fullført (Antatt)

28. mai 2027

Datoer for studieregistrering

Først innsendt

20. august 2026

Først innsendt som oppfylte QC-kriteriene

20. august 2026

Først lagt ut (Faktiske)

24. august 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

24. august 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

20. august 2026

Sist bekreftet

1. juli 2026

Mer informasjon

Begreper knyttet til denne studien

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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