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A Phase I Study to Assess the Safety, Tolerability and PK of Ceftazidime-Avibactam in Healthy Chinese Subjects

Phase 1
Completed
Conditions
Healthy Volunteers
Interventions
Drug: 0.9% Normal Saline
Registration Number
NCT01920399
Lead Sponsor
Pfizer
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
42
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CAZ-AVICAZ-AVIIV infusion of AVI 500 mg + CAZ 2000 mg.
Placebo0.9% Normal SalineIV infusions of 0.9% normal saline
Primary Outcome Measures
NameTimeMethod
Safety and Tolerability:Adverse events, vital signs, ECGs, clinical laboratory measurements, physical examinations, oral body temperatureRoutine safety assessments, throughout the period that subjects receive CAZ-AVI/PLACEBO up to 5 days following discontinuation of study treatment

AE: The onset of an AE relative to treatment will be calculated as the time difference between the onset (date and time) of the AE and the start time of the last dose (date and time) prior to the AE; the duration of a resolved AE will be calculated as the difference between the resolution (date and time) of the AE and the onset (date and time) of the AE. Vital signs and oral temperature:Change in BP, pulse rate and oral temperature at each post treatment time point will be calculated as the post treatment measurement value minus the baseline value observed on Day -1. Physical examination: complete physical examination and brief physical examination. ECG: heart rate, RR, PR, QRS, and QT intervals from the 12-lead ECG and the derived variable QTcF. Safety laboratory (hematology, chemistry and urinalysis): Change in laboratory test value at each post treatment time point will be calculated as the post treatment value minus the baseline value observed on Day -1 .

Secondary Outcome Measures
NameTimeMethod
Plasma PK parameters for CAZ and AVI of multi dose: the trough concentration CminDays 6, 7, 8
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)Day 1 and Day 9
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.single IV infusion on Day 1
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.After repeated infusion On Day 9

Trial Locations

Locations (1)

Research Site

🇨🇳

Shanghai, China

Research Site
🇨🇳Shanghai, China

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