A Study to Investigate the Effect of Administration of Ceftazidime-avibactam (CAZ-AVI) and Ceftaroline Fosamil -Avibactam (CXL) on the Intestinal Flora of Healthy Volunteers

NCT01789528 | Completed Phase 1

• 1 other identifier: D4280C00023
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the effect of administration of CAZ-AVI and CXL on the intestinal flora of male and female healthy volunteers after multiple administrations over 7 days. An assessment of the effect on intestinal flora is an important aspect to understand for the safe clinical use of the investigational products and is expected by regulatory agencies.

Conditions

Pharmacokinetics; Open Label; CAZ-AVI; CXL; Effect on Intestinal Flora; Safety

Keywords

Phase I,; open label,; CAZ-AVI,; CXL,; healthy volunteers,; intestinal flora.

Outcome Measures

Primary Outcomes (1)

• Changes in the intestinal flora of healthy subjects after administration of ceftazidime-avibactam (CAZ-AVI) and ceftaroline fosamil -avibactam (CXL).

  The number and types of microorganisms in faeces.

  Change from baseline (Day-1) at Day 2, 5, 7, 10, 14 and 21

Secondary Outcomes (5)

• Safety and tolerability

  Screening up to 12 days after discharge from study site

• Pharmacokinetics of CAZ-AVI in healthy volunteers

  Days 1, 2 and 5: Pre-dose and 2 hours post dose. Day 7: pre-dose, 0.5, 1, 1.5, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 6, 8, 12, and 24 hours post dose (Day 8)

• Pharmacokinetics of CXL in healthy volunteers

  Days 1, 2 and 5: Pre-dose and 1 hour post dose. Day 7: pre-dose, 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 5, 7, 8, 12, and 24 hours post dose (Day 8)

• To measure CAZ-AVI and CXL plasma and faecal concentrations using bioactivity techniques.

  Day -1, 2, 5, 7, 10, 14 and 21

• To describe the in vitro susceptibility of new colonizing bacteria of the intestinal microflora to CAZ-AVI and CXL during and after CAZ-AVI and CXL administration.

  Day -1, 2, 5, 7, 10, 14 and 21

Study Arms (1)

CAZ-AVI or CXL

EXPERIMENTAL

Cohort 1: CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) by intravenous infusion given over 2 hours, every 8 hours Cohort 2: CXL (600 mg ceftaroline fosamil and 600 mg avibactam)

Drug: CAZ-AVI; Drug: CXL

Interventions

CAZ-AVI DRUG

IV infusion

Also known as: Cohort 1

CAZ-AVI or CXL

CXL DRUG

IV infusion

Also known as: Cohort 2

CAZ-AVI or CXL

Eligibility Criteria

• Age: 18 Years - 45 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 volunteers aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venepuncture.
• Females: Female healthy volunteers are authorised to participate in this study if both of the following criteria are met:
• A negative serum pregnancy test BOTH at screening AND at admission to the study centre.
• Agrees not to attempt pregnancy while receiving investigational product and for a period of 7 days after last investigational product administration, and agrees to the use of acceptable methods of contraception (according to instructions) prior to, during, and for 7 days after the last investigational product administration.
• Have a body mass index (BMI) between 19 and 30 kg/m2.

You may not qualify if:

• History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant abnormalities in physical examination, ECG, clinical chemistry, haematology, coagulation, or urinalysis results, as judged by the investigator.
• Pregnant or breastfeeding female healthy volunteers.
• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the healthy volunteer at risk because of participation in the study, or influence the results or the healthy volunteer's ability to participate in the study.
• Known history of Clostridium difficile infection in last 3 months.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Research Site

Stockholm, Sweden

Location

MeSH Terms

Interventions

KPNA1 protein, human

Study Officials

• Paul Newell, MD

  AstraZeneca R&D, Alderly Park, Mereside, SK 104TG, Macclesfield, Cheshire, United Kingdom

  STUDY DIRECTOR

• Sandhia Ponnarambil, MD

  AstraZeneca R&D Alderly Park, Parklands, SK 104TF, Macclesfield, Cheshire, United Kingdom

  STUDY CHAIR

• Georgios Panagiotidis, MD

  Clinical Pharmacology Trial Unit, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 4, 2013
• First Posted: February 12, 2013
• Study Start: August 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: September 5, 2017

Record last verified: 2017-09

Locations

SE (1)