NCT02620774

Brief Summary

This study will determine the tissue penetration of ceftolozane/tazobactam (Zerbaxa, Merck \& Co.), a novel β-lactam/β-lactamase combination antibiotic, into the extracellular, interstitial fluid of soft tissue in diabetic patients with lower limb wound infections. Penetration will be compared with a group of healthy volunteer control participants.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1 diabetes

Timeline
Completed

Started Feb 2016

Longer than P75 for phase_1 diabetes

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 1, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 3, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

February 19, 2016

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2017

Completed
1.8 years until next milestone

Results Posted

Study results publicly available

January 15, 2019

Completed
Last Updated

January 15, 2019

Status Verified

October 1, 2017

Enrollment Period

1.1 years

First QC Date

December 1, 2015

Results QC Date

October 27, 2017

Last Update Submit

July 31, 2018

Conditions

DiabetesWound InfectionHealthy Volunteers

Outcome Measures

Primary Outcomes (2)

  • Ceftolozane Tissue Penetration

    The ratio of ceftolozane tissue concentration area under the curve (AUC) to plasma concentrations AUC following the final (i.e., 3rd) ceftolozane/tazobactam dose. Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma and dialysate concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of ceftolozane AUC in blood and tissue.

    16-24 hours

  • Tazobactam Tissue Penetration

    The ratio of tazobactam tissue concentration area under the curve (AUC) to plasma concentration AUC following the final (3rd) ceftolozane/tazobactam dose. Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma and dialysate concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of tazobactam AUC in blood and tissue.

    16-24 hours

Secondary Outcomes (5)

  • Ceftolozane Area Under the Curve (AUC) in Tissue

    16 to 24 hours post-dose

  • Tazobactam AUC in Tissue

    16 to 24 hours post-dose

  • Ceftolozane Total Drug AUC in Plasma

    16 to 24 hours post-dose

  • Tazobactam Total Drug AUC in Plasma

    16 to 24 hours post-dose

  • Number of Participants With Adverse Events

    Duration of study (34 hours)

Study Arms (2)

Diabetic Wound Infection

EXPERIMENTAL

Participants with a documented history of Type 1 or Type 2 diabetes and a mild to moderate (Grade 2 or 3) wound infection of the lower limb will receive at least 3 doses of intravenous ceftolozane/tazobactam 1.5g every 8 hours, followed by sampling of interstitial tissue fluid at the margin of the wound by a microdialysis probe over 8 hours.

Drug: Ceftolozane/tazobactamProcedure: Microdialysis Catheter Insertion

Healthy Volunteer

ACTIVE COMPARATOR

Participants will be male or female healthy adult volunteers with no significant medical or medication history. Participants will receive at least 3 doses of intravenous ceftolozane/tazobactam 1.5g every 8 hours, followed by sampling of interstitial tissue fluid in the thigh by a microdialysis probe over 8 hours.

Drug: Ceftolozane/tazobactamProcedure: Microdialysis Catheter Insertion

Interventions

Ceftolozane/tazobactamDRUG

3 or more doses of ceftolozane/tazobactam intravenously administered over 60 minutes every 8 hours

Also known as: Zerbaxa
Diabetic Wound InfectionHealthy Volunteer
Microdialysis Catheter InsertionPROCEDURE

A 20 kila-Dalton microdialysis probe (63 MD catheter; MDialysis Inc., N. Chelmsford, MA) will be inserted into the subcutaneous tissue at the margin of the wound (patient group) or in the thigh tissue (healthy volunteers). The probe will be left in place for the final dose and all tissue sampling procedures thereafter. This probe is perfused with a physiologic solution to collect interstitial fluid samples. The probe will then be removed after completion of sample collection.

Diabetic Wound InfectionHealthy Volunteer

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Experimental: Type 1 or Type 2 diabetes and a mild to moderate (Grade 2 or 3) wound infection of the lower limb
  • Active Comparator: Healthy Adult Volunteer

You may not qualify if:

  • All Participants:
  • Less than 18 years of age
  • History of hypersensitivity to ceftolozane/tazobactam, piperacillin/tazobactam, or any β-lactam antibiotic
  • History of hypersensitivity to lidocaine or lidocaine derivatives
  • Females who are pregnant or breastfeeding
  • Concomitant receipt of any β-lactams antibiotic
  • Concomitant receipt of probenecid
  • Reduced kidney function defined as creatinine clearance of ≤ 50 mL/min
  • Any other reason felt by the investigator to potentially affect the outcomes of the study
  • Experimental Group Only:
  • No palpable pedal pulses present
  • Participants likely to require multiple surgical interventions during the study period, which therefore could affect placement of the microdialysis catheter
  • Active Comparator Group Only:
  • Positive urine drug screen (cocaine, tetrahydrocannabinol, opiates, benzodiazepines, and amphetamines)
  • History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Related Publications (1)

  • Monogue ML, Stainton SM, Baummer-Carr A, Shepard AK, Nugent JF, Kuti JL, Nicolau DP. Pharmacokinetics and Tissue Penetration of Ceftolozane-Tazobactam in Diabetic Patients with Lower Limb Infections and Healthy Adult Volunteers. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e01449-17. doi: 10.1128/AAC.01449-17. Print 2017 Dec.

    PMID: 28893779DERIVED

MeSH Terms

Conditions

Diabetes MellitusWound Infection

Interventions

ceftolozane, tazobactam drug combination

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesInfections

Limitations and Caveats

No clinical or microbiological outcome data were collected; patient and volunteers were not matched based on demographic data; interference with the plasma assay was observed in two patients.

Results Point of Contact

Title
David Nicolau
Organization
Center for Anti-infective Research and Development
david.nicolau@hhchealth.org
860-972-3941

Study Officials

  • David P Nicolau, PharmD

    Harford Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 1, 2015

First Posted

December 3, 2015

Study Start

February 19, 2016

Primary Completion

April 1, 2017

Study Completion

April 1, 2017

Last Updated

January 15, 2019

Results First Posted

January 15, 2019

Record last verified: 2017-10

Data Sharing

IPD Sharing
Will not share

Locations

US(1)