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

20 augusti 2026 uppdaterad 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.

Studieöversikt

Status

Har inte rekryterat ännu

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Beräknad)

30

Fas

  • Fas 1

Kontakter och platser

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

Studiekontakt

Studieorter

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

  • Vuxen
  • Äldre vuxen

Tar emot friska volontärer

Ja

Beskrivning

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

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: Icke-randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Grupp 1
Deltagare med lätt nedsatt leverfunktion (CP Klass A, poäng 5 eller 6)
Single oral dose of AZD4144 in participants from all groups
Experimentell: Group 2
Deltagare med måttlig leverfunktionsnedsättning (CP-klass B, poäng 7 till 9).
Single oral dose of AZD4144 in participants from all groups
Experimentell: 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
Experimentell: 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

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
PK parameters AUCinf
Tidsram: 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
Tidsram: 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)
Tidsram: 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
Tidsram: Day 0 through Day 7 or 9
maximum observed plasma concentration
Day 0 through Day 7 or 9

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
PK parameters tmax
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: Day 0 through Day 3
renal clearance from urine concentration
Day 0 through Day 3
PK parameters Ae determined from urine concentration
Tidsram: 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
Tidsram: Day 0 through Day 3
Percentage of unchanged drug excreted into the urine
Day 0 through Day 3
PK Parameters tlast
Tidsram: Day 0 through Day 7 or 9
time of last quantifiable concentration
Day 0 through Day 7 or 9
PK Parameters λz
Tidsram: Day 0 through Day 7 or 9
terminal elimination rate constant
Day 0 through Day 7 or 9
PK Parameters AUC(0-24)
Tidsram: 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)
Tidsram: Day 0 through Day 3
area under the plasma concentration-time curve from time 0 to 72 hours postdose
Day 0 through Day 3

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

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 (Beräknad)

24 augusti 2026

Primärt slutförande (Beräknad)

28 maj 2027

Avslutad studie (Beräknad)

28 maj 2027

Studieregistreringsdatum

Först inskickad

20 augusti 2026

Först inskickad som uppfyllde QC-kriterierna

20 augusti 2026

Första postat (Faktisk)

24 augusti 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

24 augusti 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

20 augusti 2026

Senast verifierad

1 juli 2026

Mer information

Termer relaterade till denna studie

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

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