A Study to Assess the Levels of CAZ-AVI and Metronidazole in the Blood When Given Together and Separately - Full Text View

Purpose

The purpose of the study is to assess whether there is any pharmacokinetic interactions between CAZ-AVI and metronidazole.

Condition	Intervention	Phase
Healthy	Drug: CAZ-AVI Drug: metronidazole Drug: CAZ-AVI + metronidazole	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	A Phase I, Open-Label, 3-way Crossover, Pharmacokinetic and Drug-Drug Interaction Study of Ceftazidime Avibactam (CAZ-AVI) and Metronidazole When Administered Alone and in Combination in Healthy Subjects

Resource links provided by NLM:

MedlinePlus related topics: Drug Reactions

Drug Information available for: Metronidazole Metronidazole benzoate Metronidazole hydrochloride Ceftazidime sodium Ceftazidime

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components [ Time Frame: CAZ-AVI: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.5, 2.75, 3, 4, 5, 7, 11, 23, 73, 73.5, 74, 74.5, 75, 75.25, 75.5, 75.75, 76, 77, 78, 80, 84 and 95 hours post-dose ] [ Designated as safety issue: No ]
Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components [ Time Frame: Metronidazole: pre-dose, 0.5, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 72, 72.5, 73, 73.25, 73.5, 74, 75, 76, 78, 80, 84 and 96 hours post-dose ] [ Designated as safety issue: No ]
Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components [ Time Frame: CAZ-AVI and metronidazole: pre-dose, 0.5, 1, 1.25, 1.5, 2.5, 3, 3.25, 3.5, 3.75, 4, 5, 6, 8, 12, 24, 72, 72.5, 73, 73.25, 73.5, 74, 74.5, 75, 75.25, 75.5, 75.75, 76, 77, 78, 80, 84 and 96 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess safety and tolerability of CAZ-AVI and metronidazole when administered as a 2- and 1-hour infusion, respectively, every 8 hours by assessment of adverse events, lab, vital signs, ECG, physical examination [ Time Frame: Screening up to 26 days after first dose ] [ Designated as safety issue: Yes ]

Enrollment:	28
Study Start Date:	February 2012
Study Completion Date:	July 2012
Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: CAZAVI CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)	Drug: CAZ-AVI Infusion
Active Comparator: Metronidazole Metronidazole (500 mg)	Drug: metronidazole Infusion
Active Comparator: CAZAVI+metronidazole CAZ-AVI (2000mg ceftazidime/500 mg avibactam) + metronidazole (500 mg)	Drug: CAZ-AVI + metronidazole Infusion

Detailed Description:

A Phase I, Open-Label, 3-way Crossover, Pharmacokinetic and Drug-Drug Interaction Study of ceftazidime avibactam (CAZ-AVI) and Metronidazole when Administered Alone and in Combination in Healthy Subjects

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 aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture; female subjects must be post menopausal or surgically sterile.
Male subjects should be willing to use barrier contraception ie, condoms, from the first day of the investigational product administration until 3 months after the last administration of the investigational product.
Have a body mass index (BMI) between 19 and 30 kg/m2
Be able to understand and willing to comply with study procedures, restrictions, and requirements, as judged by the Investigator

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
Known history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to carbapenem or cephalosporin antibiotics or other beta-actam antibiotics or any other investigational product to be administered as part of the study
Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks prior to the first administration of investigational product Any clinically significant abnormalities in physical examination, ECG, clinical chemistry, haematology, or urinalysis results, as judged by the Investigator

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01534247

Locations

United States, Kansas
Research site
Overland Park, Kansas, United States

Sponsors and Collaborators

AstraZeneca

Cerexa, Inc.

Investigators

Study Chair:	Mirjana Kujacic, MD	AstraZenecaMolndal Sweden
Principal Investigator:	David Mathews, MD	QuintilesOverland Park, US
Study Director:	Paul Newell	Astrazeneca Alderly UK

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01534247 History of Changes
Other Study ID Numbers:	D4280C00012
Study First Received:	February 9, 2012
Last Updated:	July 9, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

Phase I
drug to drug
CAZ-AVI
Healthy volunteer

pharmacokinetics
open label
metronidazole
safety

Additional relevant MeSH terms:

Ceftazidime
Metronidazole
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on May 19, 2013