Plasma og intrapulmonal farmakokinetikk av Ceftibuten og Ledaborbactam hos friske mannlige og kvinnelige deltakere 18 til ≤55 år
En fase 1, åpen studie for å evaluere sikkerheten og plasma- og intrapulmonal farmakokinetikk til Ceftibuten og Ledaborbactam hos friske voksne deltakere
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
-
-
Arizona
-
Phoenix, Arizona, Forente stater, 85032
- Pulmonary Associates
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
Tar imot friske frivillige
Beskrivelse
Inkluderingskriterier:
- Friske voksne 18-55 år
- Hanner eller ikke-gravide, ikke-ammende hunner
- Kroppsmasseindeks: ≥18 og ≤32 kg/m2
- Forsert ekspirasjonsvolum på 1 sekund av minst 80 % av antatt verdi
- Laboratorieverdier som oppfyller definerte inngangskriterier
Ekskluderingskriterier:
- Anamnese med legemiddelallergi eller overfølsomhet overfor penicillin, cefalosporin eller β-laktam antibakterielt legemiddel eller for medisiner brukt under en bronkoskopi
- Tilstander som potensielt endrer absorpsjon og/eller utskillelse av oralt administrerte legemidler
- Anamnese eller tilstedeværelse av betydelige sykdommer, inkludert enhver klinisk relevant akutt sykdom eller operasjon innen de siste 3 månedene
- Positiv bruk/test av alkohol, narkotika eller tobakk
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Group 1
Participants in Group 1 underwent one standardized bronchoscopy with bronchoalveolar lavage after the fifth dose of ceftibuten-ledaborbactam etzadroxil.
|
Five doses of ledaborbactam etzadroxil administered orally every 12 hours
Five doses of ceftibuten administered orally every 12 hours
|
|
Eksperimentell: Group 2
Participants in Group 2 underwent one standardized bronchoscopy with bronchoalveolar lavage after the fifth of dose of ceftibuten alone.
|
Five doses of ceftibuten administered orally every 12 hours
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Intrapulmonary PK - AUC0-12 at Steady State in Group 1: Ceftibuten and Ledaborbactam Etzadroxil
Tidsramme: 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
Tidsramme: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
The pharmacokinetic parameter (PK) Cmax of ceftibuten assessed at at steady-state.
|
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Plasma Area Under the Curve From Time Zero to 12 Hours (AUC0-12) for Ceftibuten
Tidsramme: 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
|
|
Plasma Maximum Concentration (Cmax) of Ledaborbactam Etzadroxil
Tidsramme: Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
The pharmacokinetic parameter (PK) Cmax of ledaborbactam etzadroxil assessed at at steady-state.
|
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Plasma AUC0-12h for Ledaborbactam Etzadroxil
Tidsramme: 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.
|
Samples were taken at 0, 2, 4, 6, 8, and 12 hours post 5th dose
|
|
Ratios of Drug Exposure for Ledaborbactam Etzadroxil and Ceftibuten
Tidsramme: 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
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftibuten and Ledaborbactam Etzadroxil
Tidsramme: Up to Day 8
|
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.
|
Up to Day 8
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Studieleder: Kamal Hamed, MD, MPH, Basilea Pharmaceutica International Ltd, Allschwil
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- VNRX-7145-105
- HHSN272201600029C (Annet stipend/finansieringsnummer: National Institute of Allergy and Infectious Diseases)
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
produkt produsert i og eksportert fra USA
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .