DiabetesPhase 1NCT02620774

Tissue Penetration of Ceftolozane/Tazobactam in Diabetic Patients With Lower Limb Infections

A Phase 1 study testing Ceftolozane/tazobactam and Microdialysis Catheter Insertion in people with Diabetes and Wound Infection, run by Hartford Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Diabetes, Wound Infection, Healthy Volunteers
What is being tested?: Ceftolozane/tazobactam and Microdialysis Catheter Insertion
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteUnited States
Study dates: 19 Feb 2016to Apr 2017
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 17Show fewer

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.
Use of tobacco- or nicotine-containing products in excess of the equivalence of 5 cigarettes per day.
Use of prescription or nonprescription drugs, vitamins, or dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, with the exception of acetaminophen at doses of ≤ 1 g/day. Herbal supplements, hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing intrauterine devices (IUDs), postcoital contraceptive methods), and hormone replacement therapy must be discontinued at least 14 days prior to the first dose of study medication. Depo-Provera® must be discontinued at least 6 months prior to the first dose of study medication.

Trial locations and contacts

1 site in 1 country.

United States1 site

Hartford Hospital
Hartford, Connecticut, 06102

Other trials in United States

About this study

Read the detailed description

This study will enroll 10 patients with diabetes who are admitted with a lower limb wound infection and 6 healthy volunteer control participants. The study will take place in an inpatient unit at Hartford Hospital for all patients and in the Clinical Research Center at Hartford Hospital for all healthy volunteers. All participants will receive at least 3 doses of ceftolozane/tazobactam 1.5g every 8 hours. A microdialysis probe (Mdialysis Inc., N. Chelmsford MA) will be inserted into the subcutaneous soft tissue near the margin of the wound (patients) or in the thigh (healthy volunteers). The microdialysis probe is perfused with lactated Ringer's solution and samples are collected each hour for 8 hours after the final dose. A peripheral intravenous catheter will be inserted into an arm vein to collect blood samples simultaneously with microdialysis samples. Concentrations in tissue are compared with blood to determine percent penetration.

Conditions: Diabetes, Wound Infection, Healthy Volunteers
Being tested: Ceftolozane/tazobactam, Microdialysis Catheter Insertion
Medical subject headings: Diabetes Mellitus, Wound Infection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ceftolozane/tazobactamDrug
Also called Zerbaxa
3 or more doses of ceftolozane/tazobactam intravenously administered over 60 minutes every 8 hours
Microdialysis Catheter InsertionProcedure or surgery
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.

Study groups in NCT02620774
Study group	Role	What they receive
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. Receives: Drug: Ceftolozane/tazobactam; Procedure: 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. Receives: Drug: Ceftolozane/tazobactam; Procedure: Microdialysis Catheter Insertion

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 16-24 hours

Secondary outcomes (5)

Ceftolozane Area Under the Curve (AUC) in Tissue
The ceftolozane AUC in tissue from 16 to 24 hours.
Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. 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.
Measured: 16 to 24 hours post-dose
Tazobactam AUC in Tissue
The tazobactam AUC in tissue over 16 to 24 hours
Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. 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.
Measured: 16 to 24 hours post-dose
Ceftolozane Total Drug AUC in Plasma
The ceftolozane total drug AUC in plasma over 16 to 24 hours
Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma 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.
Measured: 16 to 24 hours post-dose
Tazobactam Total Drug AUC in Plasma
The tazobactam total drug AUC in plasma over 16 to 24 hours
Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma 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.
Measured: 16 to 24 hours post-dose
Number of Participants With Adverse Events
Number of reported or documented adverse events recorded during participation in the study.
Measured: Duration of study (34 hours)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Feb 2016Apr 2017

First posted3 Dec 2015 (estimated)
Study start19 Feb 2016
Primary completionApr 2017
Study completionApr 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02620774
Sponsor's protocol ID: Nicolau-53433
Status last verified: Oct 2017
First submitted: 1 Dec 2015
Last updated: 15 Jan 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 28893779

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Tissue Penetration of Ceftolozane/Tazobactam in Diabetic Patients With Lower Limb Infections
ClinicalTrials.gov ID: NCT02620774
Acronym / sponsor ID: Nicolau-53433
Conditions: Diabetes, Wound Infection, Healthy Volunteers
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Hartford HospitalUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: 19 Feb 2016 (actual)
Primary completion: Apr 2017 (actual)
Study completion: Apr 2017 (actual)
First posted: 3 Dec 2015 (estimated)
Results: Posted 15 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Diabetic Wound Infection	Experimental	Drug: Ceftolozane/tazobactam, Procedure: Microdialysis Catheter InsertionParticipants 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.
Healthy Volunteer	Active comparator	Drug: Ceftolozane/tazobactam, Procedure: Microdialysis Catheter InsertionParticipants 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (17 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ceftolozane/tazobactamAlso: Zerbaxa3 or more doses of ceftolozane/tazobactam intravenously administered over 60 minutes every 8 hours	Drug	Diabetic Wound Infection, Healthy Volunteer
Microdialysis Catheter InsertionA 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.	Procedure or surgery	Diabetic Wound Infection, Healthy Volunteer

Primary outcome

Ceftolozane Tissue Penetration
Time frame: 16-24 hours
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.
Tazobactam Tissue Penetration
Time frame: 16-24 hours
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.

5 secondary outcomes

Ceftolozane Area Under the Curve (AUC) in Tissue
Time frame: 16 to 24 hours post-dose
Tazobactam AUC in Tissue
Time frame: 16 to 24 hours post-dose
Ceftolozane Total Drug AUC in Plasma
Time frame: 16 to 24 hours post-dose
Tazobactam Total Drug AUC in Plasma
Time frame: 16 to 24 hours post-dose
Number of Participants With Adverse Events
Time frame: Duration of study (34 hours)

Results and safety

Results posted to the registry on 15 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Diabetic Wound Infection	10	10
Healthy Volunteer	6	6

Primary outcome: Ceftolozane Tissue Penetration

Time frame: 16-24 hours. Median (Full Range). Unit: ratio

Measure	Diabetic Wound Infection n = 10	Healthy Volunteer n = 6
Value	0.75 (0.35 to 1.00)	0.87 (0.54 to 2.20)

Primary outcome: Tazobactam Tissue Penetration

Time frame: 16-24 hours. Median (Full Range). Unit: ratio

Measure	Diabetic Wound Infection n = 7	Healthy Volunteer n = 6
Value	1.18 (0.54 to 1.44)	0.85 (0.63 to 2.10)

Population analysed: Seven of the 10 enrolled participants in the Diabetic Wound Infection cohort provided data for tazobactam in plasma. Assay interference was observed in samples for two participants, and one participant had concentrations below the lower limit of the detection for the assay. This explains the difference with participant flow numbers.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected until study completion (approximately 34 hours). All abnormal laboratory determinations were followed until resolution unless follow-up is determined to be unnecessary by the study physician. For the control group, participants were discharged from the study after a 4 hour monitoring period from removal of microdialysis catheters.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Diabetic Wound Infection	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Healthy Volunteer	0 of 6 (0%)	0 of 6 (0%)	0 of 6

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28893779Monogue 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David P Nicolau, PharmD principal investigator

Harford Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ceftolozane/tazobactam and Microdialysis Catheter Insertion in people with Diabetes and Wound Infection, run by Hartford Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ceftolozane Tissue Penetration (time frame: 16-24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02620774, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2019.