Study to Assess the Concentration of Avibactam and Ceftazidime in Epithelial Lining Fluid and Plasma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Healthy	Drug: CAZ104	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	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

Resource links provided by NLM:

Drug Information available for: Ceftazidime sodium Ceftazidime

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

To measure and compare the concentration of Avibactam and Ceftazidime in ELF and plasma [ Time Frame: at several timepoints from pre-dose up to 5 days post dose (Part 2) ] [ Designated as safety issue: No ]
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:

To evaluate safety and tolerability of Avibactam and Ceftazidime [ Time Frame: at several timepoints from pre-dose up to 5 days post dose ] [ Designated as safety issue: Yes ]
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

Enrollment:	45
Study Start Date:	August 2011
Study Completion Date:	July 2012
Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 CAZ104 (2000mg Ceftazidime/500mg Avibactam)	Drug: CAZ104 IV Infusion Other Name: CAZ104 (2000mg Ceftazidime/500mg Avibactam)
Experimental: 2 CAZ104 (3000mg Ceftazidime/1000mg Avibactam)	Drug: CAZ104 IV Infusion Other Name: CAZ104 (3000mg Ceftazidime/1000mg Avibactam)

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

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01395420

Locations

United Kingdom
Research Site
London, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	Paul Newell, MD	AstraZeneca
Principal Investigator:	Leonard Siew, MBCHB, MRCP(UK)	Quintiles Phase I unit London
Study Chair:	Mirjana Kujacic, MD	AstraZeneca

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01395420 History of Changes
Other Study ID Numbers:	D4280C00009
Study First Received:	July 14, 2011
Last Updated:	August 16, 2012
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:

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

Additional relevant MeSH terms:

Ceftazidime
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013