Farmacocinética plasmática e intrapulmonar de ceftibuteno e ledaborbactam em participantes saudáveis do sexo masculino e feminino de 18 a ≤55 anos de idade
Um estudo aberto de fase 1 para avaliar a segurança e a farmacocinética plasmática e intrapulmonar de ceftibuteno e ledaborbactam em participantes adultos saudáveis
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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 estudo
Inscrição (Real)
Estágio
- Fase 1
Contactos e Locais
Locais de estudo
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Arizona
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Phoenix, Arizona, Estados Unidos, 85032
- Pulmonary Associates
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-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
Aceita Voluntários Saudáveis
Descrição
Critérios de inclusão:
- Adultos saudáveis de 18 a 55 anos
- Homens ou mulheres não grávidas e não lactantes
- Índice de Massa Corporal: ≥18 e ≤32 kg/m2
- Volume expiratório forçado em 1 segundo de pelo menos 80% do valor previsto
- Valores laboratoriais que atendem aos critérios de entrada definidos
Critérios de exclusão:
- História de alergia a medicamentos ou hipersensibilidade à penicilina, cefalosporina ou medicamento antibacteriano β-lactâmico ou a medicamentos usados durante uma broncoscopia
- Condições que potencialmente alteram a absorção e/ou excreção de medicamentos administrados por via oral
- História ou presença de doenças significativas, incluindo qualquer doença aguda clinicamente relevante ou cirurgia nos últimos 3 meses
- Uso/teste positivo de álcool, drogas ou tabaco
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
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
|
|
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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Prazo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
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
Prazo: 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
Prazo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
The PK parameter AUC0-12 for ceftibuten assessed at at steady-state.
|
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
Prazo: 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
Prazo: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
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
Prazo: 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
|
|
Ratios of Drug Exposure for Ceftibuten
Prazo: 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
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Prazo: 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
- Diretor de estudo: Kamal Hamed, MD, MPH, Basilea Pharmaceutica International Ltd, Allschwil
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- VNRX-7145-105
- HHSN272201600029C (Número de outro subsídio/financiamento: National Institute of Allergy and Infectious Diseases)
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