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Completed

NCT Number: NCT01430910

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

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.

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Key information

Conditions

Healthy Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Infections Intraabdominal Infections Male Urogenital Diseases Urinary Tract Infections Urogenital Diseases Urologic Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research site

London, United Kingdom

About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

CAZ104

Drug

IV infusion

Avibactam

Drug

IV infusion

ceftazidime

Drug

IV infusion

Primary outcomes

  1. 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

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

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)]

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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

    Time frame: 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)]

    Time frame: 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)

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: Up to 24 hours post last dose

Secondary outcomes

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

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

    Time frame: Up to 24 hours post last dose

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

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

Important dates

Study start
2011
Primary completion
2012
Study completion
2012
First posted
Sep 9, 2011
Registry last updated
Sep 1, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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