Clinical trial NCT01920399: A Phase I Study to Assess the Safety, Tolerability and PK of Ceftazidime-Avibactam in Healthy Chinese Subjects
Official title: A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Ceftazidime-Avibactam Administered as Single and Repeated Intravenous Doses in Healthy Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: CAZ-AVI China phase I PK study
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-08-12
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Investigate the safety and tolerability, as well as PK profile of ceftazidime-avibactam (CAZ -AVI) administered in single and repeated intravenous (IV) infusions in healthy Chinese subjects.This study data will be used to support CAZ-AVI NDA in China.


Eligibility criteria: Key Inclusion Criteria:

* Provision of signed and dated, written informed consent prior to any study-specific procedures.
* Healthy male and female (of non-child bearing potential) Chinese subjects, with suitable veins for cannulation or repeated venipuncture
* BMI 19 to 24 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg.

Key Exclusion Criteria:

* Any clinical condition requiring the regular use of any medication.
* Consumption of alcohol, drug, tobacco (cigarettes).
* Sensitive to any food, or any serious reaction to carbapenem, cephalosporin, or other β-lactam antibiotics.
* Severe medical or psychiatric condition or laboratory abnormality.
* Blood donation.
* 12 lead ECG abnormal.

Primary outcomes:
measure: Safety and Tolerability:Adverse events, vital signs, ECGs, clinical laboratory measurements, physical examinations, oral body temperature
timeFrame: Routine safety assessments, throughout the period that subjects receive CAZ-AVI/PLACEBO up to 5 days following discontinuation of study treatment
Secondary outcomes:
measure: Plasma PK parameters for CAZ and AVI of single dose: Cmax, tmax, Clast, tlast, AUC(0-t), AUC, AUC(0-8), λz, t1/2, Vss, Vz, CL, MRT, etc.
timeFrame: single IV infusion on Day 1
measure: Plasma PK parameters for CAZ and AVI of multi dose: the trough concentration Cmin
timeFrame: Days 6, 7, 8
measure: Plasma PK parameters for CAZ and AVI of repeated infusion: Cmax, tmax, Clast, tlast, AUC(0-t), AUC, AUC(0-8), λz, t1/2, Vss, Vz, CL, MRT, etc.
timeFrame: After repeated infusion On Day 9
measure: Urine PK parameters for CAZ and AVI of single and repeated infusion: Cumulated urinary excretion (amount), percentage of cumulated urinary recovery (% dose) and renal clearance (CLr)
timeFrame: Day 1 and Day 9
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Research Site
Study officials:
affiliation: Shuguang Hospital affiliated with Shanghai University of TCM
name: Furong Qiu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li J, Learoyd M, Qiu F, Zhu L, Edeki T. A Randomized, Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Ceftazidime-Avibactam in Healthy Chinese Subjects. Clin Drug Investig. 2016 Feb;36(2):119-26. doi: 10.1007/s40261-015-0347-x.
citation: 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.