NCT02421120

Brief Summary

There is established evidence that adult patients with Cystic Fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Ceftolozane/Tazobactam is a newly approved broad spectrum intravenous antibiotic, which has potent in vitro activity against multidrug resistant Pseudomonas aeruginosa, the most common pathogen implicated in CF pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of ceftolozane/tazobactam in 20 adult CF patients admitted for a pulmonary exacerbation at one of 4 participating hospitals in the US. Patients will remain on standard of care IV antibiotics and receive 4-6 doses of ceftolozane/tazobactam 3 grams every 8 hours. Blood will be sampled after the final dose to determine concentrations and pharmacokinetics of ceftolozane and tazobactam. Safety and tolerability will be assessed throughout the 3 day study.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
21

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Sep 2015

Shorter than P25 for phase_4

Geographic Reach
1 country

4 active sites

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

April 13, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 20, 2015

Completed
4 months until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2016

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
6 months until next milestone

Results Posted

Study results publicly available

April 13, 2017

Completed
Last Updated

August 4, 2020

Status Verified

July 1, 2020

Enrollment Period

6 months

First QC Date

April 13, 2015

Results QC Date

February 28, 2017

Last Update Submit

July 27, 2020

Conditions

Cystic FibrosisCystic Fibrosis Pulmonary ExacerbationPseudomonas Aeruginosa Infection

Outcome Measures

Primary Outcomes (4)

  • Ceftolozane Clearance

    This outcome determines the clearance of ceftolozane over the 8 hour dosing interval.

    0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose

  • Ceftolozane Volume of Distribution (Central Compartment)

    This outcome determines the volume of distribution of ceftolozane over the 8 hour dosing interval.

    0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose

  • Tazobactam Clearance

    This outcome determines the clearance of tazobactam over the 8 hour dosing interval.

    0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose

  • Tazobactam Volume of Distribution (Central Compartment)

    This outcome determines the volume of distribution of tazobactam over the 8 hour dosing interval.

    0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose

Secondary Outcomes (1)

  • Ceftolozane Probability of Target Attainment at 8 mcg/ml

    24 hours

Study Arms (1)

Ceftolozane/Tazobactam

EXPERIMENTAL

Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses

Drug: Ceftolozane/Tazobactam

Interventions

Ceftolozane/TazobactamDRUG

1 hour intravenous infusion

Also known as: Zerbaxa, CXA-101
Ceftolozane/Tazobactam

Eligibility Criteria

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

You may qualify if:

  • Age 18 years or older
  • Documented diagnosis of CF
  • Acute pulmonary exacerbation as the primary reason for admission to the hospital with requirement to receive systemic antibiotic treatment
  • If female, subjects must be non-pregnant and non-lactating. Females can be either not of a child-bearing potential or if of a child-bearing potential, on acceptable modes of birth control such as abstinence from sexual intercourse, oral/parenteral contraceptives, or barrier method

You may not qualify if:

  • History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic (a history of mild rash to a cephalosporin followed by uneventful re-exposure is not a contraindication)
  • Prior (within 24 hours of first dose of study drug) or concomitant receipt of piperacillin/tazobactam or probenecid
  • History of lung transplant
  • Moderate to severe renal dysfunction defined as a creatinine clearance \< 50 mL/min (as calculated by the Cockcroft-Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis
  • A hemoglobin less than 8 gm/dl at baseline
  • Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator)
  • Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data
  • Planned or prior participation in any other interventional drug study within 30 days

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

University of North Carolina Medical Center

Chapel Hill, North Carolina, 27599, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Related Publications (1)

  • Monogue ML, Pettit RS, Muhlebach M, Cies JJ, Nicolau DP, Kuti JL. Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6578-6584. doi: 10.1128/AAC.01566-16. Print 2016 Nov.

    PMID: 27550351RESULT

MeSH Terms

Conditions

Cystic FibrosisPseudomonas Infections

Interventions

ceftolozane, tazobactam drug combinationceftolozane

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInfant, Newborn, DiseasesGram-Negative Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Results Point of Contact

Title
Dr. Joseph L. Kuti, PharmD
Organization
Hartford Hospital
joseph.kuti@hhchealth.org
860-972-3612

Study Officials

  • Joseph L Kuti, PharmD

    Hartford Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
OTHER
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Director, Clinical and Economic Studies

Study Record Dates

First Submitted

April 13, 2015

First Posted

April 20, 2015

Study Start

September 1, 2015

Primary Completion

March 1, 2016

Study Completion

October 1, 2016

Last Updated

August 4, 2020

Results First Posted

April 13, 2017

Record last verified: 2020-07

Locations

US(4)