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

NCT01534247 | Completed Phase 1

• 1 other identifier: D4280C00012
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Phase I; drug to drug; CAZ-AVI; Healthy volunteer; pharmacokinetics; open label; metronidazole; safety

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• 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

Study Arms (3)

CAZAVI

EXPERIMENTAL

CAZ-AVI (2000 mg ceftazidime/500 mg avibactam)

Drug: CAZ-AVI

Metronidazole

ACTIVE COMPARATOR

Metronidazole (500 mg)

Drug: metronidazole

CAZAVI+metronidazole

ACTIVE COMPARATOR

CAZ-AVI (2000mg ceftazidime/500 mg avibactam) + metronidazole (500 mg)

Drug: CAZ-AVI + metronidazole

Interventions

CAZ-AVI DRUG

Infusion

CAZAVI

metronidazole DRUG

Infusion

Metronidazole

CAZ-AVI + metronidazole DRUG

Infusion

CAZAVI+metronidazole

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead
• Forest Laboratories: collaborator

Study Sites (1)

Research site

Overland Park, Kansas, United States

Location

Related Publications (1)

• 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.

  PMID: 26516584 BACKGROUND

Related Links

• Redaction of D4280C00012 Protocol

MeSH Terms

Interventions

Metronidazole

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mirjana Kujacic, MD

  AstraZenecaMolndal Sweden

  STUDY CHAIR

• David Mathews, MD

  QuintilesOverland Park, US

  PRINCIPAL INVESTIGATOR

• Paul Newell

  Astrazeneca Alderly UK

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2012
• First Posted: February 16, 2012
• Study Start: February 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: September 5, 2017

Record last verified: 2017-09

Locations

US (1)