Plasma- en intrapulmonale farmacokinetiek van ceftibuten en ledaborbactam bij gezonde mannelijke en vrouwelijke deelnemers van 18 tot ≤55 jaar oud
Een fase 1, open-label onderzoek om de veiligheid en plasma- en intrapulmonale farmacokinetiek van ceftibuten en ledaborbactam bij gezonde volwassen deelnemers te evalueren
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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Arizona
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Phoenix, Arizona, Verenigde Staten, 85032
- Pulmonary Associates
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
Accepteert gezonde vrijwilligers
Beschrijving
Inclusiecriteria:
- Gezonde volwassenen 18-55 jaar
- Mannetjes of niet-drachtige, niet-zogende vrouwtjes
- Body Mass Index: ≥18 en ≤32 kg/m2
- Geforceerd uitademingsvolume in 1 seconde van minimaal 80% van de voorspelde waarde
- Laboratoriumwaarden die voldoen aan gedefinieerde toelatingscriteria
Uitsluitingscriteria:
- Voorgeschiedenis van geneesmiddelenallergie of overgevoeligheid voor penicilline, cefalosporine of β-lactam antibacteriële geneesmiddelen of voor medicijnen gebruikt tijdens een bronchoscopie
- Omstandigheden die mogelijk de absorptie en/of uitscheiding van oraal toegediende geneesmiddelen veranderen
- Voorgeschiedenis of aanwezigheid van significante ziekten, inclusief klinisch relevante acute ziekten of operaties in de afgelopen 3 maanden
- Positief gebruik/test van alcohol, drugs of tabak
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: 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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Experimenteel: 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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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
|
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Ratios of Drug Exposure for Ceftibuten
Tijdsspanne: 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
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Tijdsspanne: 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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Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie directeur: Kamal Hamed, MD, MPH, Basilea Pharmaceutica International Ltd, Allschwil
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
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Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- VNRX-7145-105
- HHSN272201600029C (Ander subsidie-/financieringsnummer: National Institute of Allergy and Infectious Diseases)
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
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