Farmacocinética plasmática e intrapulmonar de ceftibuten y ledaborbactam en participantes masculinos y femeninos sanos de 18 a ≤ 55 años de edad
Un estudio abierto de fase 1 para evaluar la seguridad y la farmacocinética plasmática e intrapulmonar de ceftibuteno y ledaborbactam en participantes adultos sanos
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
In Group 1, participants were to receive a total of five oral doses of ceftibuten ledaborbactam etzadroxil (600 mg ceftibuten/600 mg ledaborbactam etzadroxil) every 12 hours. Following the fifth dose, each participant was to undergo one standardized bronchoscopy with bronchoalveolar lavage (BAL) at one of five designated timepoints (2, 4, 6, 8, and 12 hours), with five participants assigned to each timepoint.
In Group 2, participants were to receive a total of five doses of 600 mg oral ceftibuten alone every 12 hours. After the last dose, each participant was to undergo one standardized bronchoscopy with BAL at one of two designated timepoints (4 and 12 hours), with three participants assigned to each timepoint.
Blood samples to determine plasma concentrations of ceftibuten, ledaborbactam etzadroxil (Group 1 only), and urea were to be collected at the designated timepoints.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Arizona
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Phoenix, Arizona, Estados Unidos, 85032
- Pulmonary Associates
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
Acepta Voluntarios Saludables
Descripción
Criterios de inclusión:
- Adultos sanos 18-55 años
- Machos o hembras no gestantes ni lactantes
- Índice de Masa Corporal: ≥18 y ≤32 kg/m2
- Volumen espiratorio forzado en 1 segundo de al menos el 80% del valor previsto
- Valores de laboratorio que cumplen con los criterios de entrada definidos.
Criterios de exclusión:
- Antecedentes de alergia a medicamentos o hipersensibilidad a la penicilina, cefalosporina o antibacterianos β-lactámicos o a medicamentos utilizados durante una broncoscopia.
- Condiciones que potencialmente alteran la absorción y/o excreción de medicamentos administrados por vía oral.
- Antecedentes o presencia de enfermedades importantes, incluida cualquier enfermedad aguda clínicamente relevante o cirugía en los últimos 3 meses
- Prueba/consumo positivo de alcohol, drogas o tabaco
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 |
|---|---|
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Experimental: Group 1
Participants in Group 1 underwent one standardized bronchoscopy with bronchoalveolar lavage after the fifth dose of ceftibuten-ledaborbactam etzadroxil.
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Five doses of ledaborbactam etzadroxil administered orally every 12 hours
Five doses of ceftibuten administered orally every 12 hours
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Experimental: Group 2
Participants in Group 2 underwent one standardized bronchoscopy with bronchoalveolar lavage after the fifth of dose of ceftibuten alone.
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Five doses of ceftibuten administered orally every 12 hours
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Periodo de tiempo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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The PK parameter AUC0-12 for ceftibuten and ledaborbactam etzadroxil was assessed by standardized bronchoscopy with bronchoalveolar lavage (BAL). BAL samples were collected from each participant at one of five designated time points (2, 4, 6, 8, and 12 hours). The first aspirate was collected separately (BAL 1), while the second through the fourth aspirates were pooled (BAL 2). Mean concentration values at each BAL sampling time point were determined, and data from all sampling times were combined into a single dataset to calculate the AUC0-12 value for each matrix. AUC 0-12 was estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF concentration at one time point, so the pharmacokinetic parameters for ELF were calculated using the arithmetic mean concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF across all participants. |
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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Plasma Maximum Concentration (Cmax) of Ceftibuten
Periodo de tiempo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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The pharmacokinetic parameter (PK) Cmax of ceftibuten assessed at at steady-state.
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Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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Plasma Area Under the Curve From Time Zero to 12 Hours (AUC0-12) for Ceftibuten
Periodo de tiempo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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The PK parameter AUC0-12 for ceftibuten assessed at at steady-state.
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Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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Plasma Maximum Concentration (Cmax) of Ledaborbactam Etzadroxil
Periodo de tiempo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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The pharmacokinetic parameter (PK) Cmax of ledaborbactam etzadroxil assessed at at steady-state.
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Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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Plasma AUC0-12h for Ledaborbactam Etzadroxil
Periodo de tiempo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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The pharmacokinetic parameter (PK) AUC0-12h of ledaborbactam etzadroxil assessed at at steady-state.
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Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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Ratios of Drug Exposure for Ledaborbactam Etzadroxil and Ceftibuten
Periodo de tiempo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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Drug penetration ratio of epithelial lining fluid (ELF) to unbound plasma were assessed using the AUC values for each matrix for BAL 1 and BAL 2. BAL samples were collected from each participant at one of five designated time points (2, 4, 6, 8, and 12 hours). The first aspirate was collected separately (BAL 1), while the second through the fourth aspirates were pooled (BAL 2). All pharmacokinetic parameters (PK) were estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF concentration at one time point, so the PK parameters for ELF were calculated using the arithmetic mean concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF across all participants. |
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Ratios of Drug Exposure for Ceftibuten
Periodo de tiempo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
Drug penetration ratio of epithelial lining fluid (ELF) to unbound plasma were assessed using the AUC values for each matrix for BAL 1 and BAL 2. BAL samples were collected from each participant at one of five designated time points (2, 4, 6, 8, and 12 hours). The first aspirate was collected separately (BAL 1), while the second through the fourth aspirates were pooled (BAL 2). All pharmacokinetic parameters (PK) were estimated using Phoenix WinNonlin Non-compartmental analysis. Each participant only contributed one ELF concentration at one time point, so the PK parameters for ELF were calculated using the arithmetic mean concentration at each BAL sampling time point, resulting in a single parameter estimate of ELF across all participants. |
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Periodo de tiempo: Up to Day 8
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A TEAE was defined as any event not present prior to the first administration of the study drug, or any event already present that worsens in either severity or frequency following exposure to the study drug.
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Up to Day 8
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Director de estudio: Kamal Hamed, MD, MPH, Basilea Pharmaceutica International Ltd, Allschwil
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
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
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- VNRX-7145-105
- HHSN272201600029C (Otro número de subvención/financiamiento: National Institute of Allergy and Infectious Diseases)
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.
producto fabricado y exportado desde los EE. UU.
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