Cystic FibrosisPhase 4NCT02421120
Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients
A Phase 4 study testing Ceftolozane/Tazobactam in people with Cystic Fibrosis and Cystic Fibrosis Pulmonary Exacerbation, run by Joseph L. Kuti, PharmD at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis, Cystic Fibrosis Pulmonary Exacerbation, Pseudomonas Aeruginosa Infection
- What is being tested?
- Ceftolozane/Tazobactam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 4 sitesUnited States
- Study dates
- Sep 2015to Oct 2016
- Phase
- Phase 4
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of North Carolina Medical Center
Chapel Hill, North Carolina, 27599
Hartford Hospital
Hartford, Connecticut, 06102
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
About this study
Official title: A Prospective, Multicenter, Open-Label Study to Assess Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients Admitted With Acute Pulmonary Exacerbation
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.
Read the detailed description
Participants will receive 4-6 doses of ceftolozane/tazobactam 3 grams every 8 hours, in addition to standard intravenous antibiotic therapy selected by the site. Just prior and then after the final dose, a total of six blood samples will be collected to measure ceftolozane and tazobactam concentrations. Data will be fit to a population pharmacokinetic model. The final model will be utilized in a Monte Carlo simulation to determine the probability of several different dosing regimens retaining concentrations above the minimum inhibitory concentration (MIC) for at least 39% of the dosing interval. These data will be utilized to determine an optimized dosing regimen for adults with CF.
- Being tested
- Ceftolozane/Tazobactam
- Medical subject headings
- Cystic Fibrosis, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftolozane/TazobactamDrug
Also called Zerbaxa, CXA-101
1 hour intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Ceftolozane/Tazobactam | Experimental | Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Receives: Drug: Ceftolozane/Tazobactam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ceftolozane Clearance
This outcome determines the clearance of ceftolozane over the 8 hour dosing interval.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
This simulated outcome indicates the likelihood that ceftolozane will retain drug concentrations above the MIC for >/= 60% of the dosing interval at an MIC of 8 mcg/ml when administered as a 3g (2g ceftolozane/1g tazobactam) every 8 hour dose infused over 1 hour. This analysis is conducted via a Monte Carlo simulation using the population pharmacokinetic parameter estimates and dispersion from the 20 participants who contributed pharmacokinetic data to the study.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2015 (estimated)
- Study startSep 2015
- Primary completionMar 2016
- Study completionOct 2016
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 Cystic FibrosisStudies 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 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph L. Kuti, PharmD
- Sponsor type
- University, hospital or other
- Collaborators
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA), Indiana University Health, University of North Carolina, St. Christopher's Hospital for Children
- Responsible party
- Sponsor-investigator, Joseph L. Kuti, PharmD, Hartford Hospital
- Investigators
- Joseph L Kuti, PharmD, Principal investigator, Hartford Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02421120
- Sponsor's protocol ID
- HHC-2015-0107
- Status last verified
- Jul 2020
- First submitted
- 13 Apr 2015
- Last updated
- 4 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 27550351
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Open-Label Study to Assess Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients Admitted With Acute Pulmonary Exacerbation
- ClinicalTrials.gov ID
- NCT02421120
- Acronym / sponsor ID
- HHC-2015-0107
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Joseph L. Kuti, PharmDUniversity, hospital or other
- Collaborators
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA), Indiana University Health, University of North Carolina, St. Christopher's Hospital for Children
- Study start
- Sep 2015
- Primary completion
- Mar 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 20 Apr 2015 (estimated)
- Results
- Posted 13 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Participants will receive 4-6 doses of ceftolozane/tazobactam 3 grams every 8 hours, in addition to standard intravenous antibiotic therapy selected by the site. Just prior and then after the final dose, a total of six blood samples will be collected to measure ceftolozane and tazobactam concentrations. Data will be fit to a population pharmacokinetic model. The final model will be utilized in a Monte Carlo simulation to determine the probability of several different dosing regimens retaining concentrations above the minimum inhibitory concentration (MIC) for at least 39% of the dosing interval. These data will be utilized to determine an optimized dosing regimen for adults with CF.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ceftolozane/Tazobactam | Experimental | Drug: Ceftolozane/TazobactamCeftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
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: Zerbaxa, CXA-1011 hour intravenous infusion | Drug | Ceftolozane/Tazobactam |
Primary outcome
Ceftolozane Clearance
Time frame: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose
This outcome determines the clearance of ceftolozane over the 8 hour dosing interval.
Ceftolozane Volume of Distribution (Central Compartment)
Time frame: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose
This outcome determines the volume of distribution of ceftolozane over the 8 hour dosing interval.
Tazobactam Clearance
Time frame: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose
This outcome determines the clearance of tazobactam over the 8 hour dosing interval.
Tazobactam Volume of Distribution (Central Compartment)
Time frame: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose
This outcome determines the volume of distribution of tazobactam over the 8 hour dosing interval.
1 secondary outcome
Ceftolozane Probability of Target Attainment at 8 mcg/ml
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27550351Monogue 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.
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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.
Joseph L Kuti, PharmD principal investigator
Hartford Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ceftolozane/Tazobactam in people with Cystic Fibrosis and Cystic Fibrosis Pulmonary Exacerbation, run by Joseph L. Kuti, PharmD at 4 sites 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 4 inclusion and 8 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 4 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 13 Apr 2017). 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 Clearance (time frame: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose). The study lists 4 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 NCT02421120, 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 4 Aug 2020.