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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01395420
First received: July 14, 2011
Last updated: August 16, 2012
Last verified: August 2012
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 22, 2014