A Study to Assess the Levels of Two Antibiotics in the Blood When Given Together and Separately

Phase 1CompletedNCT01430910

Pfizer43 enrolled

Overview

This is a randomised study divided into 2 parts. Part A investigates the effect of prolonged dosing (ten days) with Avibactam and Ceftazidime when given together and how this will effect how much Avibactam and Ceftazidime enters the blood. Part B investigates how much Avibactam (NXL104) and Ceftazidime enter the blood when Avibactam and Ceftazidine are given separately or together intravenously.

A Phase I, 2-Part, Open-Label, Pharmacokinetic and Drug-Drug Interaction Study of CAZ104 (Avibactam and Ceftazidime in Healthy Subjects)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

43

Conditions

Interventions

IV infusion

IV infusion

CeftazidimeDRUG

IV infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Provision of signed and dated, written informed consent prior to any study specific procedures * Healthy male and female subjects aged 18 to 50 years 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 admi * Male subjects should be willing to use barrier contraception ie, condoms, from dosing to 3 months after dosing with the IP (investigational product). * 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 of any clinically significant disease or disorder 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 * History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to avibactam, ceftazidime, and/or excipients * Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IP Prolonged QTcF (\>450 ms) or shortened QTcF (\<350 ms) or a family history of long QT syndrome

Locations (1)

Research site

London, United Kingdom

Outcomes

Primary Outcomes

Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including maximum plasma concentration (Cmax)

Time frame: Up to 24 hours post last dose

Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including time of Cmax (tmax)

Time frame: Up to 24 hours post last dose

Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including minimum plasma concentration (Cmin)

Time frame: Up to 24 hours post last dose

Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including time of Cmin (tmin)

Time frame: Up to 24 hours post last dose

Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including last quantifiable plasma concentration (Clast)

Time frame: Up to 24 hours post last dose

Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including time of Clast (tlast)

Time frame: Up to 24 hours post last dose

Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including average plasma concentration during a dosing interval (Cavg)

Time frame: Up to 24 hours post last dose

Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including fluctuation index

Time frame: Up to 24 hours post last dose

Data from ClinicalTrials.gov

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Secondary Outcomes

To assess safety and tolerability of Avibactam by assessment of Adverse events

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Avibactam by clinical laboratory assessments

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Avibactam by assessment of vital signs

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Avibactam by assessment of safety electrocardiogram

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Avibactam by assessment of physical examination

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Avibactam by assessment of withdrawn

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Ceftazidime by assessment of Adverse events

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Ceftazidime by clinical laboratory assessments

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Ceftazidime by assessment of vital signs

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Ceftazidime by assessment of safety electrocardiogram

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Ceftazidime by assessment of physical examination

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of Ceftazidime by assessment of withdrawn

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of CAZ104 by assessment of Adverse events

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of CAZ104 by clinical laboratory assessments

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of CAZ104 by assessment of vital signs

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of CAZ104 by assessment of safety electrocardiogram

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of CAZ104 by assessment of physical examination

Time frame: Up to 24 hours post last dose

To assess safety and tolerability of CAZ104 by assessment of withdrawn

Time frame: Up to 24 hours post last dose

NCT01430910 - A Study to Assess the Levels of Two Antibiotics in the Blood When Given Together and Separately | Crick | Crick