Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT01789528
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01789528
Recruitment Status : Completed
First Posted : February 12, 2013
Last Update Posted : September 5, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE February 4, 2013
First Posted Date  ICMJE February 12, 2013
Last Update Posted Date September 5, 2017
Study Start Date  ICMJE August 2013
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
Changes in the intestinal flora of healthy subjects after administration of ceftazidime-avibactam (CAZ-AVI) and ceftaroline fosamil -avibactam (CXL). [ Time Frame: Change from baseline (Day-1) at Day 2, 5, 7, 10, 14 and 21 ]
The number and types of microorganisms in faeces.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
  • Safety and tolerability [ Time Frame: Screening up to 12 days after discharge from study site ]
    Adverse event, ECG, safety laboratory assessments, physical examinations and vital signs.
  • Pharmacokinetics of CAZ-AVI in healthy volunteers [ Time Frame: 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) ]
    On Day 7, the following pharmacokinetic parameters will be calculated when applicable: Maximum plasma concentration (Cmax), time of Cmax (tmax), time of last quantifiable plasma concentration (last), area under the plasma concentration-time curve during the dosing interval (AUC(0-τ)), area under the plasma concentration time curve from zero to the time of the last quantifiable concentration (AUC(0-t)), half-life (t½), systemic plasma clearance (CL), apparent plasma clearance (CL/F), volume of distribution at steady state (Vss), and apparent volume of distribution (Vz/F).
  • Pharmacokinetics of CXL in healthy volunteers [ Time Frame: 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) ]
    On Day 7, the following pharmacokinetic parameters will be calculated when applicable: Maximum plasma concentration (Cmax), time of Cmax (tmax), time of last quantifiable plasma concentration (last), area under the plasma concentration-time curve during the dosing interval (AUC(0-τ)), area under the plasma concentration time curve from zero to the time of the last quantifiable concentration (AUC(0-t)), half-life (t½), systemic plasma clearance (CL), apparent plasma clearance (CL/F), volume of distribution at steady state (Vss), and apparent volume of distribution (Vz/F).
  • To measure CAZ-AVI and CXL plasma and faecal concentrations using bioactivity techniques. [ Time Frame: Day -1, 2, 5, 7, 10, 14 and 21 ]
    The concentrations of CAZ-AVI and CXL will be determined in plasma and faecal samples.
  • 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. [ Time Frame: Day -1, 2, 5, 7, 10, 14 and 21 ]
    Minimal inhibitory concentration (MIC) for CAZ-AVI and CXL will be determined for new colonizing bacteria from faecal samples.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase 1, Open-label, Multiple-dose, Single Centre Study to Investigate the Effect of Administration of CAZ-AVI and CXL on the Intestinal Flora of Healthy Volunteers.
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Pharmacokinetics
  • Open Label
  • CAZ-AVI
  • CXL
  • Effect on Intestinal Flora
  • Safety
Intervention  ICMJE
  • Drug: CAZ-AVI
    IV infusion
    Other Name: Cohort 1
  • Drug: CXL
    IV infusion
    Other Name: Cohort 2
Study Arms  ICMJE Experimental: CAZ-AVI or CXL

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)

Interventions:
  • Drug: CAZ-AVI
  • Drug: CXL
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2014)
48
Original Estimated Enrollment  ICMJE
 (submitted: February 11, 2013)
28
Actual Study Completion Date  ICMJE March 2014
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provision of signed and dated, written informed consent prior to any study specific procedures
  2. 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:

    1. A negative serum pregnancy test BOTH at screening AND at admission to the study centre.
    2. 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.
  3. Have a body mass index (BMI) between 19 and 30 kg/m2.

Exclusion Criteria:

  1. 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.
  2. Any clinically significant abnormalities in physical examination, ECG, clinical chemistry, haematology, coagulation, or urinalysis results, as judged by the investigator.
  3. Pregnant or breastfeeding female healthy volunteers.
  4. 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.
  5. Known history of Clostridium difficile infection in last 3 months.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01789528
Other Study ID Numbers  ICMJE D4280C00023
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Paul Newell, MD AstraZeneca R&D, Alderly Park, Mereside, SK 104TG, Macclesfield, Cheshire, United Kingdom
Study Chair: Sandhia Ponnarambil, MD AstraZeneca R&D Alderly Park, Parklands, SK 104TF, Macclesfield, Cheshire, United Kingdom
Principal Investigator: Georgios Panagiotidis, MD Clinical Pharmacology Trial Unit, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden
PRS Account Pfizer
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP