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Study to Assess the Concentration of Avibactam and Ceftazidime in Epithelial Lining Fluid and Plasma

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT01395420
Lead Sponsor
Pfizer
Brief Summary

This is an open-label study divided in 2 parts and 3 cohorts to determine the concentration of Avibactam and Ceftazidime in the lining of the lungs and the blood.

Detailed Description

A Phase I Open-Label, 2-Part, 3-Cohort, Single-Centre Study to Assess the Concentration of Avibactam and Ceftazidime in Epithelial Lining Fluid and Plasma Using at Least Two Different Dosing Regimens in Healthy Volunteers

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
45
Inclusion Criteria
  • Provision of signed and dated, written informed consent prior to any study specific procedures
  • Healthy male and female subjects with veins suitable for cannulation or repeated venepuncture; female subjects must be postmenopausal or surgically sterile. Female subjects must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-child-bearing potential
  • Male subjects should be willing to use barrier contraception ie, condoms, from dosing to 3 months after dosing with the IP
  • Have a body mass index (BMI) between 19 and 30 kg/m2
  • As judged by the Investigator, all the subjects must be able to understand and be willing to comply with study procedures, restrictions and requirements
Exclusion Criteria
  • History or presence of any clinically significant disease or disorder (including a history of chronic respiratory disease eg, asthma, chronic obstructive pulmonary disease [COPD], cystic fibrosis or interstitial lung disease) which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
  • History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
  • Known allergy to lidocaine/lignocaine, midazolam, alfentanyl or other topical anaesthetics/sedatives in similar classes to these agents
  • Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IP
  • Any clinically significant abnormalities in physical examination, lung function test, ECG, clinical chemistry, haematology, coagulation screen, or urinalysis results as judged by the Investigator

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1CAZ104CAZ104 (2000mg Ceftazidime/500mg Avibactam)
2CAZ104CAZ104 (3000mg Ceftazidime/1000mg Avibactam)
Primary Outcome Measures
NameTimeMethod
To measure and compare the concentration of Avibactam and Ceftazidime in ELF and plasmaat several timepoints from pre-dose up to 5 days post dose (Part 2)

To measure and compare the concentration of Avibactam and Ceftazidime in ELF and plasma by assessment of maximum concentration (Cmax), time to Cmax (tmax), area under the concentration time curve during a dosing interval t (AUCτ), terminal half life (t½λz) in plasma and ELF, plasma clearance (CL), volume of distribution at steady state (Vss) and at the terminal phase (Vz) in plasma, ratio of Cmax in ELF over Cmax in plasma and ratio of AUCτ in ELF over AUCτ in plasma.

Secondary Outcome Measures
NameTimeMethod
To evaluate safety and tolerability of Avibactam and Ceftazidimeat several timepoints from pre-dose up to 5 days post dose

To evaluate safety and tolerability of Avibactam and Ceftazidime by assessment of adverse events (AEs), physical examinations, vital signs, 12 lead electrocardiograms (ECGs), Pulse oximetry and safety laboratory assessments

Trial Locations

Locations (1)

Research Site

🇬🇧

London, United Kingdom

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