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

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

Detailed Description
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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

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: CAZ-AVI
* Drug: metronidazole
* Drug: CAZ-AVI + metronidazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAZAVI<br>CAZ-AVI (2000 mg ceftazidime/500 mg avibactam) | Drug: CAZ-AVI<br>* Infusion<br>|
| Active Comparator: Metronidazole<br>Metronidazole (500 mg) | Drug: metronidazole<br>* Infusion<br>|
| Active Comparator: CAZAVI+metronidazole<br>CAZ-AVI (2000mg ceftazidime/500 mg avibactam) + metronidazole (500 mg) | Drug: CAZ-AVI + metronidazole<br>* Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components |  | 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 | 
| Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components |  | 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 | 
| Profile of pharmacokinetic of ceftazidime, avibactam and metronidazole when administering CAZ-AVI plus metronidazole in combination compared to administration of individual components |  | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Screening up to 26 days after first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, drug to drug, CAZ-AVI, Healthy volunteer, pharmacokinetics, open label, metronidazole, safety