Farmacocinetica plasmatica e intrapolmonare di Ceftibuten e Ledaborbactam in partecipanti sani di sesso maschile e femminile di età compresa tra 18 e ≤ 55 anni
Uno studio di fase 1 in aperto per valutare la sicurezza e la farmacocinetica plasmatica e intrapolmonare di Ceftibuten e Ledaborbactam in partecipanti adulti sani
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
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Arizona
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Phoenix, Arizona, Stati Uniti, 85032
- Pulmonary Associates
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-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
- Adulto
Accetta volontari sani
Descrizione
Criteri di inclusione:
- Adulti sani 18-55 anni
- Maschi o femmine non gravide e non in allattamento
- Indice di massa corporea: ≥18 e ≤32 kg/m2
- Volume espiratorio forzato in 1 secondo pari ad almeno l'80% del valore previsto
- Valori di laboratorio che soddisfano i criteri di ingresso definiti
Criteri di esclusione:
- Storia di allergia ai farmaci o ipersensibilità alla penicillina, alle cefalosporine o ai farmaci antibatterici β-lattamici o ai farmaci utilizzati durante una broncoscopia
- Condizioni che potenzialmente alterano l'assorbimento e/o l'escrezione di farmaci somministrati per via orale
- Storia o presenza di malattie significative, inclusa qualsiasi malattia acuta o intervento chirurgico clinicamente rilevante negli ultimi 3 mesi
- Test/uso di alcol, droghe o tabacco positivo
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: 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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Sperimentale: 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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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Lasso di tempo: 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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Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Direttore dello studio: Kamal Hamed, MD, MPH, Basilea Pharmaceutica International Ltd, Allschwil
Pubblicazioni e link utili
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Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- VNRX-7145-105
- HHSN272201600029C (Altro numero di sovvenzione/finanziamento: National Institute of Allergy and Infectious Diseases)
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