PharmacokineticsPhase 1NCT01789528
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
A Phase 1 study testing CAZ-AVI and CXL in people with Pharmacokinetics and Open Label, run by Pfizer at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics, Open Label, CAZ-AVI
- What is being tested?
- CAZ-AVI and CXL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteSweden
- Study dates
- Aug 2013to Mar 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
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
- Being tested
- CAZ-AVI, CXL
- Keywords
- Phase I,, open label,, CAZ-AVI,, CXL,, healthy volunteers,, intestinal flora.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAZ-AVIDrug
Also called Cohort 1
IV infusion
CXLDrug
Also called Cohort 2
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: CAZ-AVI; Drug: CXL |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline (Day-1) at Day 2, 5, 7, 10, 14 and 21
Secondary outcomes (5)
Safety and tolerability
Adverse event, ECG, safety laboratory assessments, physical examinations and vital signs.
Measured: Screening up to 12 days after discharge from study site
Pharmacokinetics of CAZ-AVI in healthy volunteers
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).
Measured: 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
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).
Measured: 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.
The concentrations of CAZ-AVI and CXL will be determined in plasma and faecal samples.
Measured: 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.
Minimal inhibitory concentration (MIC) for CAZ-AVI and CXL will be determined for new colonizing bacteria from faecal samples.
Measured: Day -1, 2, 5, 7, 10, 14 and 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2013 (estimated)
- Study startAug 2013
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacokineticsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Newell, MD, Study director, AstraZeneca R&D, Alderly Park, Mereside, SK 104TG, Macclesfield, Cheshire, United KingdomSandhia Ponnarambil, MD, Study chair, AstraZeneca R&D Alderly Park, Parklands, SK 104TF, Macclesfield, Cheshire, United KingdomGeorgios Panagiotidis, MD, Principal investigator, Clinical Pharmacology Trial Unit, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01789528
- Sponsor's protocol ID
- D4280C00023
- Status last verified
- Sep 2017
- First submitted
- 4 Feb 2013
- Last updated
- 5 Sep 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01789528
- Acronym / sponsor ID
- D4280C00023
- Conditions
- Pharmacokinetics, Open Label, CAZ-AVI, CXL, Effect on Intestinal Flora, Safety
- Keywords
- Phase I,, open label,, CAZ-AVI,, CXL,, healthy volunteers,, intestinal flora.
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Aug 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 12 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAZ-AVI or CXL | Experimental | Drug: CAZ-AVI, Drug: CXLCohort 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) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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:
- Have a body mass index (BMI) between 19 and 30 kg/m2.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAZ-AVIAlso: Cohort 1IV infusion | Drug | CAZ-AVI or CXL |
| CXLAlso: Cohort 2IV infusion | Drug | CAZ-AVI or CXL |
Primary outcome
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.
5 secondary outcomes
Safety and tolerability
Time frame: Screening up to 12 days after discharge from study site
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)
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)
To measure CAZ-AVI and CXL plasma and faecal concentrations using bioactivity techniques.
Time frame: 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.
Time frame: Day -1, 2, 5, 7, 10, 14 and 21
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Newell, MD study director
AstraZeneca R&D, Alderly Park, Mereside, SK 104TG, Macclesfield, Cheshire, United Kingdom
Sandhia Ponnarambil, MD study chair
AstraZeneca R&D Alderly Park, Parklands, SK 104TF, Macclesfield, Cheshire, United Kingdom
Georgios Panagiotidis, MD principal investigator
Clinical Pharmacology Trial Unit, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAZ-AVI and CXL in people with Pharmacokinetics and Open Label, run by Pfizer at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2017.