Pharmacokinetics of Ceftolozane/Tazobactam in Plasma and Cerebrospinal Fluid

NCT03309657 | Completed Phase 1 Results

• 1 other identifier: HREC/17/QRBW/117
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Ceftolozane/tazobactam is an emerging newly available antibiotic that has a broad spectrum of activity, and could be potentially useful in the management of central nervous system infections. However, data relating to penetration of ceftolozane/ tazobactam into the central nervous system, where a barrier against drug distribution exists (i.e. blood brain barrier), is currently limited. In critically ill patients this is all the more challenging as achieving adequate antibiotic concentrations even in blood is difficult. The aim of this study is to describe the concentrations achieved in the cerebrospinal fluid (i.e. bodily fluid found surrounding and inside of the brain) and blood after a single dose of ceftolozane/tazobactam administered in critically ill patients with an existing external ventricular drain (i.e. a device used in neurosurgery that relieves elevated intracranial pressure in the brain). It is planned that this information gained will help develop dosing strategies that will achieve target concentrations that will successfully treat central nervous system infections in the future.

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (4)

• Unbound Ceftolozane Exposure in the Plasma

  Unbound Ceftolozane Exposure in the plasma given by the area under the unbound concentration-time curve from time zero to infinity (AUC0-inf).

  Samples collected from 0 to 8 hours post dose at "0, 1, 2,4,6, & 8 h post dose were use estimate area under the curve from time zero to infinity estimated by non-compartmental analysis

• Unbound Tazobactam Exposure in the Plasma

  Unbound Tazobactam Exposure in the plasma given by the area under the unbound concentration-time curve from time zero to infinity (AUC0-inf).

  Samples collected from 0 to 8 hours post dose at "0, 1, 2,4,6, & 8 h post dose were use estimate area under the curve from time zero to infinity estimated by non-compartmental analysis

• Unbound Ceftolozane Exposure in the CSF

  Unbound Ceftolozane Exposure in the CSF given by the area under the unbound concentration-time curve from time zero to infinity (AUC0-inf).

  Samples collected from 0 to 8 hours post dose at "0, 1, 2,4,6, & 8 h post dose were use estimate area under the curve from time zero to infinity estimated by non-compartmental analysis

• Unbound Tazobactam Exposure in the CSF

  Unbound Tazobactam Exposure in the CSF given by the area under the unbound concentration-time curve from time zero to infinity (AUC0-inf).

  Samples collected from 0 to 8 hours post dose at "0, 1, 2,4,6, & 8 h post dose were use estimate area under the curve from time zero to infinity estimated by non-compartmental analysis

Study Arms (1)

Ceftolozane Tazobactam

EXPERIMENTAL

Infected patients with external intraventricular drain will receive a single dose of Ceftolozane/ tazobactam (3000mg) over 1 hour and will undergo blood , csf and urine sampling at specific times over an 8 hour period.

Drug: Ceftolozane/tazobactam

Interventions

Ceftolozane/tazobactam DRUG

This is an observational pharmacokinetic study whereby patients received a single dose of ceftolozane/tazobactam and plasma and cerebrospinal fluid samples were subsequently collected and analyzed to described the pharmacokinetics.

Also known as: ZERBAXA

Ceftolozane Tazobactam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with any infection requiring treatment with ceftolozane/tazobactam and who have met the following criteria:
• Age \>18 years
• The presence of an indwelling external ventricular drain (EVD) or requiring EVD insertion due to obstructive hydrocephalus/subarachnoid haemorrhage

You may not qualify if:

• Known or suspected allergy to penicillins and cephalosporins
• Pregnancy
• Receiving renal replacement therapy
• Glomerular filtration rate less than 10 mL/min
• Receiving piperacillin/tazobactam or having received piperacillin/tazobactam in the past 7 days before enrolment

Sponsors & Collaborators

• Royal Brisbane and Women's Hospital: lead
• The University of Queensland: collaborator

Study Sites (1)

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

MeSH Terms

Interventions

ceftolozane, tazobactam drug combination

Results Point of Contact

• Title: Prof. Jason Roberts
• Organization: University of Queensland Center for Clinical Research

j.roberts2@uq.edu.au

+61 7 334 65032

Study Officials

• Jason A Roberts, PhD BPharm

  Royal Brisbane and Womens Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Open label pharmacokinetic study where enrolled critically ill patients with infection receive a single dose of ceftolozane-tazobactam (in addition to other active therapy).

Study Record Dates

• First Submitted: July 30, 2017
• First Posted: October 13, 2017
• Study Start: February 1, 2018
• Primary Completion: May 1, 2020
• Study Completion: June 1, 2020
• Last Updated: September 10, 2020
• Results First Posted: September 10, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)