Clinical trial NCT01789528: 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: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Open Label
CAZ-AVI
CXL
Effect on Intestinal Flora
Safety
Keywords: Phase I,
open label,
CAZ-AVI,
CXL,
healthy volunteers,
intestinal flora.
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-02-12
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Changes in the intestinal flora of healthy subjects after administration of ceftazidime-avibactam (CAZ-AVI) and ceftaroline fosamil -avibactam (CXL).
timeFrame: Change from baseline (Day-1) at Day 2, 5, 7, 10, 14 and 21
Secondary outcomes:
measure: Safety and tolerability
timeFrame: Screening up to 12 days after discharge from study site
measure: Pharmacokinetics of CAZ-AVI in healthy volunteers
timeFrame: 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)
measure: Pharmacokinetics of CXL in healthy volunteers
timeFrame: 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)
measure: To measure CAZ-AVI and CXL plasma and faecal concentrations using bioactivity techniques.
timeFrame: Day -1, 2, 5, 7, 10, 14 and 21
measure: 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.
timeFrame: Day -1, 2, 5, 7, 10, 14 and 21
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D, Alderly Park, Mereside, SK 104TG, Macclesfield, Cheshire, United Kingdom
name: Paul Newell, MD
role: STUDY_DIRECTOR
affiliation: AstraZeneca R&D Alderly Park, Parklands, SK 104TF, Macclesfield, Cheshire, United Kingdom
name: Sandhia Ponnarambil, MD
role: STUDY_CHAIR
affiliation: Clinical Pharmacology Trial Unit, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden
name: Georgios Panagiotidis, MD
role: PRINCIPAL_INVESTIGATOR
References: