A Phase I Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144
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
Studienübersicht
Status
Status
Bedingungen
Bedingungen
Intervention / Behandlung
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Studientyp
Einschreibung (Geschätzt)
Einschreibung
Phase
Phase
- Phase 1
Kontakte und Standorte
Studienkontakt
Studienkontakt
- Name: AstraZeneca Clinical Study Information Center
- Telefonnummer: 1-877-240-9479
- E-Mail: information.center@astrazeneca.com
Studienorte
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-
Arizona
-
Mesa, Arizona, Vereinigte Staaten, 85210
- Research Site
-
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Florida
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Miami Lakes, Florida, Vereinigte Staaten, 33014
- Research Site
-
Orlando, Florida, Vereinigte Staaten, 32809
- Research Site
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Texas
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Austin, Texas, Vereinigte Staaten, 78757
- Research Site
-
-
Teilnahmekriterien
Zulassungskriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Anzahl der Arme
Waffen und Interventionen
Teilnehmergruppe / ArmTeilnehmergruppe / Arm |
Intervention / BehandlungIntervention / Behandlung |
|---|---|
|
Experimental: Gruppe 1
Teilnehmer mit leichter Leberfunktionsstörung (CP-Klasse A, Punktzahl 5 oder 6)
|
Single oral dose of AZD4144 in participants from all groups
|
|
Experimental: Gruppe 2
Teilnehmer mit moderater Leberfunktionsstörung (CP-Klasse B, Score von 7 bis 9).
|
Single oral dose of AZD4144 in participants from all groups
|
|
Experimental: 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
|
|
Experimental: 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
|
Was misst die Studie?
Primäre Ergebnismessungen
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
PK parameters AUCinf
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: Day 0 through Day 7 or 9
|
maximum observed plasma concentration
|
Day 0 through Day 7 or 9
|
Sekundäre Ergebnismessungen
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
PK parameters tmax
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: Day 0 through Day 3
|
renal clearance from urine concentration
|
Day 0 through Day 3
|
|
PK parameters Ae determined from urine concentration
Zeitfenster: 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
Zeitfenster: Day 0 through Day 3
|
Percentage of unchanged drug excreted into the urine
|
Day 0 through Day 3
|
|
PK Parameters tlast
Zeitfenster: Day 0 through Day 7 or 9
|
time of last quantifiable concentration
|
Day 0 through Day 7 or 9
|
|
PK Parameters λz
Zeitfenster: Day 0 through Day 7 or 9
|
terminal elimination rate constant
|
Day 0 through Day 7 or 9
|
|
PK Parameters AUC(0-24)
Zeitfenster: 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)
Zeitfenster: Day 0 through Day 3
|
area under the plasma concentration-time curve from time 0 to 72 hours postdose
|
Day 0 through Day 3
|
Mitarbeiter und Ermittler
Sponsor
Sponsor
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Studienbeginn
Primärer Abschluss (Geschätzt)
Primärer Abschluss
Studienabschluss (Geschätzt)
Studienabschluss
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Zuerst gepostet
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes Update gepostet
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Andere Studien-ID-Nummern
Andere Studien-ID-Nummern
- D9441C00007
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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