Plasma- und intrapulmonale Pharmakokinetik von Ceftibuten und Ledaborbactam bei gesunden männlichen und weiblichen Teilnehmern im Alter von 18 bis ≤ 55 Jahren
Eine offene Phase-1-Studie zur Bewertung der Sicherheit sowie der Plasma- und intrapulmonalen Pharmakokinetik von Ceftibuten und Ledaborbactam bei gesunden erwachsenen Teilnehmern
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 1
Kontakte und Standorte
Studienorte
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Arizona
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Phoenix, Arizona, Vereinigte Staaten, 85032
- Pulmonary Associates
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-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
Akzeptiert gesunde Freiwillige
Beschreibung
Einschlusskriterien:
- Gesunde Erwachsene zwischen 18 und 55 Jahren
- Männer oder nicht schwangere, nicht stillende Frauen
- Body-Mass-Index: ≥18 und ≤32 kg/m2
- Forciertes Exspirationsvolumen in 1 Sekunde von mindestens 80 % des vorhergesagten Werts
- Laborwerte, die definierte Eingabekriterien erfüllen
Ausschlusskriterien:
- Vorgeschichte einer Arzneimittelallergie oder Überempfindlichkeit gegen Penicillin, Cephalosporin oder β-Lactam-Antibiotika oder gegen Medikamente, die während einer Bronchoskopie verwendet werden
- Zustände, die möglicherweise die Absorption und/oder Ausscheidung oral verabreichter Arzneimittel verändern
- Anamnese oder Vorliegen bedeutender Erkrankungen, einschließlich aller klinisch relevanten akuten Erkrankungen oder Operationen innerhalb der letzten 3 Monate
- Positiver Alkohol-, Drogen- oder Tabakkonsum/Test
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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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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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Zeitfenster: 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
|
|
Plasma Maximum Concentration (Cmax) of Ceftibuten
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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.
|
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
Zeitfenster: 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
Zeitfenster: 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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Zeitfenster: 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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Mitarbeiter und Ermittler
Sponsor
Ermittler
- Studienleiter: Kamal Hamed, MD, MPH, Basilea Pharmaceutica International Ltd, Allschwil
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- VNRX-7145-105
- HHSN272201600029C (Andere Zuschuss-/Finanzierungsnummer: National Institute of Allergy and Infectious Diseases)
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Produkt, das in den USA hergestellt und aus den USA exportiert wird
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