Clinical trial NCT01395420: Study to Assess the Concentration of Avibactam and Ceftazidime in Epithelial Lining Fluid and Plasma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-07-15
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Eligibility 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

Primary outcomes:
measure: To measure and compare the concentration of Avibactam and Ceftazidime in ELF and plasma
timeFrame: at several timepoints from pre-dose up to 5 days post dose (Part 2)
Secondary outcomes:
measure: To evaluate safety and tolerability of Avibactam and Ceftazidime
timeFrame: at several timepoints from pre-dose up to 5 days post dose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Paul Newell, MD
role: STUDY_DIRECTOR
affiliation: Quintiles Phase I unit London
name: Leonard Siew, MBCHB, MRCP(UK)
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Mirjana Kujacic, MD
role: STUDY_CHAIR
References:
citation: 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.