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HealthyPhase 1NCT01430910

A Study to Assess the Levels of Two Antibiotics in the Blood When Given Together and Separately

A Phase 1 study testing CAZ104, Avibactam and Ceftazidime in people with Healthy, run by Pfizer at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a randomised study divided into 2 parts. Part A investigates the effect of prolonged dosing (ten days) with Avibactam and Ceftazidime when given together and how this will effect how much Avibactam and Ceftazidime enters the blood. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
CAZ104, Avibactam and Ceftazidime
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited Kingdom
Study dates
Sep 2011to Oct 2012
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 50 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 subjects aged 18 to 50 years with veins suitable for cannulation or repeated venepuncture; female subjects must be postmenopausal or surgically sterile. Female subjects must have a negative pregnancy test at screening and on admi
  • Male subjects should be willing to use barrier contraception ie, condoms, from dosing to 3 months after dosing with the IP (investigational product).
  • Have a body mass index (BMI) between 19 and 30 kg/m2
  • As judged by the Investigator, all the subjects must be able to understand and be willing to comply with study procedures, restrictions and requirements

Who cannot join

  • 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
  • History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to avibactam, ceftazidime, and/or excipients
  • Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IP Prolonged QTcF (>450 ms) or shortened QTcF (<350 ms) or a family history of long QT syndrome

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Research site

    London

Other trials in United Kingdom

About this study

Official title: A Phase I, 2-Part, Open-Label, Pharmacokinetic and Drug-Drug Interaction Study of CAZ104 (Avibactam and Ceftazidime in Healthy Subjects)

This is a randomised study divided into 2 parts. Part A investigates the effect of prolonged dosing (ten days) with Avibactam and Ceftazidime when given together and how this will effect how much Avibactam and Ceftazidime enters the blood. Part B investigates how much Avibactam (NXL104) and Ceftazidime enter the blood when Avibactam and Ceftazidine are given separately or together intravenously.

Read the detailed description

A Phase I, 2-Part, Open-Label, Pharmacokinetic and Drug-Drug Interaction Study of CAZ104 (Avibactam and Ceftazidime in Healthy Subjects)

Conditions
Healthy
Being tested
CAZ104, Avibactam, Ceftazidime
Keywords
Phase 1, open label, ceftazidime, pharmacokinetics, urinary tract infection, intra-abdominal infection
Medical subject headings
Urinary Tract Infections, Intraabdominal Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CAZ104Drug

    IV infusion

  • AvibactamDrug

    IV infusion

  • CeftazidimeDrug

    IV infusion

Study groups in NCT01430910
Study groupRoleWhat they receive
1ExperimentalCAZ104 (2000mg Ceftazidime/500mg Avibactam)
Receives: Drug: CAZ104
2Active comparator500mg Avibactam
Receives: Drug: Avibactam
3Active comparator2000mg Ceftazidime
Receives: Drug: Ceftazidime

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including maximum plasma concentration (Cmax)

    Measured: Up to 24 hours post last dose

  2. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including time of Cmax (tmax)

    Measured: Up to 24 hours post last dose

  3. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including minimum plasma concentration (Cmin)

    Measured: Up to 24 hours post last dose

  4. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including time of Cmin (tmin)

    Measured: Up to 24 hours post last dose

  5. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including last quantifiable plasma concentration (Clast)

    Measured: Up to 24 hours post last dose

  6. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including time of Clast (tlast)

    Measured: Up to 24 hours post last dose

  7. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including average plasma concentration during a dosing interval (Cavg)

    Measured: Up to 24 hours post last dose

  8. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including fluctuation index

    Measured: Up to 24 hours post last dose

  9. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including area under the curve of plasma drug concentration (AUC) - time curve from zero to the time of the last quantifiable concentration

    Measured: Up to 24 hours post last dose

  10. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including AUC, Day 1 only

    Measured: Up to 24 hours post last dose

  11. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including AUC during the dosing interval [AUC(0-τ)]

    Measured: Up to 24 hours post last dose

  12. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including terminal half-life (t1/2)

    Measured: Up to 24 hours post last dose

  13. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including systemic plasma clearance (CL)

    Measured: Up to 24 hours post last dose

  14. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including volume of distribution at steady state (Vss)

    Measured: Up to 24 hours post last dose

  15. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including volume of distribution at the terminal phase (Vz)

    Measured: Up to 24 hours post last dose

  16. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including accumulation ratio for Cmax and AUC(0-τ)

    Measured: Up to 24 hours post last dose

  17. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including linearity index

    Measured: Up to 24 hours post last dose

  18. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Urine pharmacokinetic variables will be measured including amount of drug excreted unchanged into urine from zero to time t [Ae(0-t)]

    Measured: Up to 24 hours post last dose

  19. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Urine pharmacokinetic variables will be measured including fraction of dose excreted unchanged into urine (fe; % dose)

    Measured: Up to 24 hours post last dose

  20. Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Urine pharmacokinetic variables will be measured including renal clearance (CLR)

    Measured: Up to 24 hours post last dose

  21. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Cmax

    Measured: Up to 24 hours post last dose

  22. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including tmax

    Measured: Up to 24 hours post last dose

  23. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Cmin

    Measured: Up to 24 hours post last dose

  24. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including tmin

    Measured: Up to 24 hours post last dose

  25. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Clast

    Measured: Up to 24 hours post last dose

  26. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including tlast

    Measured: Up to 24 hours post last dose

  27. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Cavg

    Measured: Up to 24 hours post last dose

  28. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including fluctuation index

    Measured: Up to 24 hours post last dose

  29. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including AUC(0-t)

    Measured: Up to 24 hours post last dose

  30. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including AUC, Day 1 only

    Measured: Up to 24 hours post last dose

  31. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including AUC(0-τ)

    Measured: Up to 24 hours post last dose

  32. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including t1/2

    Measured: Up to 24 hours post last dose

  33. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including CL

    Measured: Up to 24 hours post last dose

  34. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Vss

    Measured: Up to 24 hours post last dose

  35. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including Vz

    Measured: Up to 24 hours post last dose

  36. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including accumulation ratio for Cmax and AUC(0-τ)

    Measured: Up to 24 hours post last dose

  37. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Plasma pharmacokinetic variables will be measured including linearity index

    Measured: Up to 24 hours post last dose

  38. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Urine pharmacokinetic variables will be measured including Ae(0-t)

    Measured: Up to 24 hours post last dose

  39. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Urine pharmacokinetic variables will be measured including fe; % dose

    Measured: Up to 24 hours post last dose

  40. Part A: Single- and multiple-dose pharmacokinetics of Ceftazidime. Urine pharmacokinetic variables will be measured including CLR

    Measured: Up to 24 hours post last dose

  41. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Cmax

    Measured: Up to 24 hours post last dose

  42. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including tmax

    Measured: Up to 24 hours post last dose

  43. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Cmin

    Measured: Up to 24 hours post last dose

  44. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including tmin

    Measured: Up to 24 hours post last dose

  45. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Clast

    Measured: Up to 24 hours post last dose

  46. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including tlast

    Measured: Up to 24 hours post last dose

  47. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Cavg

    Measured: Up to 24 hours post last dose

  48. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including fluctuation index

    Measured: Up to 24 hours post last dose

  49. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including AUC(0-t)

    Measured: Up to 24 hours post last dose

  50. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including AUC, Day 1 only

    Measured: Up to 24 hours post last dose

  51. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including AUC(0-τ)

    Measured: Up to 24 hours post last dose

  52. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including t1/2

    Measured: Up to 24 hours post last dose

  53. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including CL

    Measured: Up to 24 hours post last dose

  54. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Vss

    Measured: Up to 24 hours post last dose

  55. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including Vz

    Measured: Up to 24 hours post last dose

  56. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including accumulation ratio for Cmax and AUC(0-τ)

    Measured: Up to 24 hours post last dose

  57. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Plasma pharmacokinetic variables will be measured including linearity index

    Measured: Up to 24 hours post last dose

  58. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Urine pharmacokinetic variables will be measured including Ae(0-t)

    Measured: Up to 24 hours post last dose

  59. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Urine pharmacokinetic variables will be measured including fe; % dose

    Measured: Up to 24 hours post last dose

  60. Part B: Pharmacokinetics of co-administering Avibactam plus Ceftazidime (CAZ104) compared to administration of the individual components. Urine pharmacokinetic variables will be measured including CLR

    Measured: Up to 24 hours post last dose

Secondary outcomes (18)

  1. To assess safety and tolerability of Avibactam by assessment of Adverse events

    Measured: Up to 24 hours post last dose

  2. To assess safety and tolerability of Avibactam by clinical laboratory assessments

    Measured: Up to 24 hours post last dose

  3. To assess safety and tolerability of Avibactam by assessment of vital signs

    Measured: Up to 24 hours post last dose

  4. To assess safety and tolerability of Avibactam by assessment of safety electrocardiogram

    Measured: Up to 24 hours post last dose

  5. To assess safety and tolerability of Avibactam by assessment of physical examination

    Measured: Up to 24 hours post last dose

  6. To assess safety and tolerability of Avibactam by assessment of withdrawn

    Measured: Up to 24 hours post last dose

  7. To assess safety and tolerability of Ceftazidime by assessment of Adverse events

    Measured: Up to 24 hours post last dose

  8. To assess safety and tolerability of Ceftazidime by clinical laboratory assessments

    Measured: Up to 24 hours post last dose

  9. To assess safety and tolerability of Ceftazidime by assessment of vital signs

    Measured: Up to 24 hours post last dose

  10. To assess safety and tolerability of Ceftazidime by assessment of safety electrocardiogram

    Measured: Up to 24 hours post last dose

  11. To assess safety and tolerability of Ceftazidime by assessment of physical examination

    Measured: Up to 24 hours post last dose

  12. To assess safety and tolerability of Ceftazidime by assessment of withdrawn

    Measured: Up to 24 hours post last dose

  13. To assess safety and tolerability of CAZ104 by assessment of Adverse events

    Measured: Up to 24 hours post last dose

  14. To assess safety and tolerability of CAZ104 by clinical laboratory assessments

    Measured: Up to 24 hours post last dose

  15. To assess safety and tolerability of CAZ104 by assessment of vital signs

    Measured: Up to 24 hours post last dose

  16. To assess safety and tolerability of CAZ104 by assessment of safety electrocardiogram

    Measured: Up to 24 hours post last dose

  17. To assess safety and tolerability of CAZ104 by assessment of physical examination

    Measured: Up to 24 hours post last dose

  18. To assess safety and tolerability of CAZ104 by assessment of withdrawn

    Measured: Up to 24 hours post last dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionOct 2012
  4. Study completionOct 2012

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01430910
Sponsor's protocol ID
D4280C00011
Status last verified
Aug 2017
First submitted
7 Sep 2011
Last updated
1 Sep 2017
Results posted
No

Publications

  • 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.

    PubMed 26516584

  • Li J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28.

    PubMed 30221827

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CAZ104, Avibactam and Ceftazidime in people with Healthy, run by Pfizer at 1 site in United Kingdom.

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 5 inclusion and 4 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 1 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 United Kingdom. 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?

Part A: Single- and multiple-dose pharmacokinetics of Avibactam. Plasma pharmacokinetic variables will be measured including maximum plasma concentration (Cmax) (time frame: Up to 24 hours post last dose). The study lists 60 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01430910, which also lists 2 linked publications.

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 1 Sep 2017.

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