Clinical trial NCT01534247: A Study to Assess the Levels of CAZ-AVI and Metronidazole in the Blood When Given Together and Separately
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Phase I
drug to drug
CAZ-AVI
Healthy volunteer
pharmacokinetics
open label
metronidazole
safety
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Forest Laboratories
First posted: 2012-02-16
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

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 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

Primary outcomes:
measure: Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components
timeFrame: 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
measure: Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components
timeFrame: 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
measure: Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components
timeFrame: 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
Secondary outcomes:
measure: 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
timeFrame: Screening up to 26 days after first dose
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Research site
state: Kansas
Study officials:
affiliation: AstraZenecaMolndal Sweden
name: Mirjana Kujacic, MD
role: STUDY_CHAIR
affiliation: QuintilesOverland Park, US
name: David Mathews, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Astrazeneca Alderly UK
name: Paul Newell
role: STUDY_DIRECTOR
References:
citation: Das S, Li J, Armstrong J, Learoyd M, Edeki T. Randomized pharmacokinetic and drug-drug interaction studies of ceftazidime, avibactam, and metronidazole in healthy subjects. Pharmacol Res Perspect. 2015 Oct;3(5):e00172. doi: 10.1002/prp2.172. Epub 2015 Aug 25.