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

NCT01395420 | Completed Phase 1

• 1 other identifier: D4280C00009
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• To evaluate safety and tolerability of Avibactam and Ceftazidime

  at several timepoints from pre-dose up to 5 days post dose

Study Arms (2)

1

EXPERIMENTAL

CAZ104 (2000mg Ceftazidime/500mg Avibactam)

Drug: CAZ104

2

EXPERIMENTAL

CAZ104 (3000mg Ceftazidime/1000mg Avibactam)

Drug: CAZ104

Interventions

CAZ104 DRUG

IV Infusion

Also known as: CAZ104 (2000mg Ceftazidime/500mg Avibactam)

1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

Related Publications (1)

• Nicolau DP, Siew L, Armstrong J, Li J, Edeki T, Learoyd M, Das S. Phase 1 study assessing the steady-state concentration of ceftazidime and avibactam in plasma and epithelial lining fluid following two dosing regimens. J Antimicrob Chemother. 2015 Oct;70(10):2862-9. doi: 10.1093/jac/dkv170. Epub 2015 Jul 1.

  PMID: 26133566 BACKGROUND

Related Links

• Clinical Study Protocol

MeSH Terms

Interventions

Ceftazidime; avibactam

Intervention Hierarchy (Ancestors)

Cephaloridine; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Paul Newell, MD

  AstraZeneca

  STUDY DIRECTOR

• Leonard Siew, MBCHB, MRCP(UK)

  Quintiles Phase I unit London

  PRINCIPAL INVESTIGATOR

• Mirjana Kujacic, MD

  AstraZeneca

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2011
• First Posted: July 15, 2011
• Study Start: August 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: September 1, 2017

Record last verified: 2017-08

Locations

GB (1)