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

NCT01920399 | Completed Phase 1

• 1 other identifier: D4280C00020
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

CAZ-AVI China phase I PK study

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability:Adverse events, vital signs, ECGs, clinical laboratory measurements, physical examinations, oral body temperature

  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 .

  Routine safety assessments, throughout the period that subjects receive CAZ-AVI/PLACEBO up to 5 days following discontinuation of study treatment

Secondary Outcomes (4)

• 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 multi dose: the trough concentration Cmin

  Days 6, 7, 8

• 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

• 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

IV infusions of 0.9% normal saline

Drug: 0.9% Normal Saline

CAZ-AVI

EXPERIMENTAL

IV infusion of AVI 500 mg + CAZ 2000 mg.

Drug: CAZ-AVI

Interventions

CAZ-AVI DRUG

A single 120 minute IV infusion on Day 1, followed by three times daily (every 8 hours, q8h) as 120 minute IV infusions for 7 days (Day 2 to Day 8), and one single 120 minute IV infusion on Day 9.

CAZ-AVI

0.9% Normal Saline DRUG

A single 120 minute IV infusion on Day 1, followed by three times daily (every 8 hours, q8h) as 120 minute IV infusions for 7 days (Day 2 to Day 8), and one single 120 minute IV infusion on Day 9.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• lead ECG abnormal.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Research Site

Shanghai, China

Location

Related Publications (2)

• 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.

  PMID: 26649741 BACKGROUND

• 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.

  PMID: 30221827 DERIVED

Related Links

• D4280C00020\_Revised\_CSP\_1\_redacted\_protocol

MeSH Terms

Interventions

Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Furong Qiu

  Shuguang Hospital affiliated with Shanghai University of TCM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2013
• First Posted: August 12, 2013
• Study Start: October 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: September 5, 2017

Record last verified: 2017-09

Locations

CN (1)