- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07783308
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
Descripción general del estudio
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: AstraZeneca Clinical Study Information Center
- Número de teléfono: 1-877-240-9479
- Correo electrónico: information.center@astrazeneca.com
Ubicaciones de estudio
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Arizona
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Mesa, Arizona, Estados Unidos, 85210
- Research Site
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Florida
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Miami Lakes, Florida, Estados Unidos, 33014
- Research Site
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Orlando, Florida, Estados Unidos, 32809
- Research Site
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Texas
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Austin, Texas, Estados Unidos, 78757
- Research Site
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Grupo 1
Participantes con insuficiencia hepática leve (CP Clase A, puntuación de 5 o 6)
|
Single oral dose of AZD4144 in participants from all groups
|
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Experimental: Grupo 2
Participantes con deterioro hepático moderado (Clase B de CP, puntuación de 7 a 9).
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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).
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Single oral dose of AZD4144 in participants from all groups
|
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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
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
PK parameters AUCinf
Periodo de tiempo: 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
Periodo de tiempo: 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
|
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PK parameters AUC(0-144)
Periodo de tiempo: 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
Periodo de tiempo: Day 0 through Day 7 or 9
|
maximum observed plasma concentration
|
Day 0 through Day 7 or 9
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
PK parameters tmax
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: Day 0 through Day 3
|
renal clearance from urine concentration
|
Day 0 through Day 3
|
|
PK parameters Ae determined from urine concentration
Periodo de tiempo: 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
Periodo de tiempo: Day 0 through Day 3
|
Percentage of unchanged drug excreted into the urine
|
Day 0 through Day 3
|
|
PK Parameters tlast
Periodo de tiempo: Day 0 through Day 7 or 9
|
time of last quantifiable concentration
|
Day 0 through Day 7 or 9
|
|
PK Parameters λz
Periodo de tiempo: Day 0 through Day 7 or 9
|
terminal elimination rate constant
|
Day 0 through Day 7 or 9
|
|
PK Parameters AUC(0-24)
Periodo de tiempo: 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)
Periodo de tiempo: Day 0 through Day 3
|
area under the plasma concentration-time curve from time 0 to 72 hours postdose
|
Day 0 through Day 3
|
Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- D9441C00007
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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