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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: CAZ104
* Drug: CAZ104


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>CAZ104 (2000mg Ceftazidime/500mg Avibactam) | Drug: CAZ104<br>* IV Infusion<br>* Other names: CAZ104 (2000mg Ceftazidime/500mg Avibactam);|
| Experimental: 2<br>CAZ104 (3000mg Ceftazidime/1000mg Avibactam) | Drug: CAZ104<br>* IV Infusion<br>* Other names: CAZ104 (3000mg Ceftazidime/1000mg Avibactam);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure and compare the concentration of Avibactam and Ceftazidime in ELF and plasma | 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. | at several timepoints from pre-dose up to 5 days post dose (Part 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and tolerability of Avibactam and Ceftazidime | 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 | at several timepoints from pre-dose up to 5 days post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, open label, healthy male and female (post menopausal) volunteers, Pharmacokinetics, CAZ104, Avibactam, Ceftazidime, open label, at least 2 different regimens, concentration of investigational product (IP), CAZ104, Avibactam, Ceftazidime, Cmax, tmax