- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04335370
Pharmacokinetics of Polymyxin B in Adult Patients With Cystic Fibrosis
Cystic fibrosis (CF) pulmonary disease is a major cause of morbidity and mortality in CF patients and is punctuated by episodes of acute exacerbation that require antibiotic treatment. Pseudomonas aeruginosa is the predominant bacterial pathogen isolated in patients with acute exacerbations, and practice guidelines recommend combination antibiotics directed against this pathogen as initial therapy. Such therapy traditionally consists of an antipseudomonal beta-lactam with either an antipseudomonal fluoroquinolone or an aminoglycoside. With growing P. aeruginosa multi-drug resistance, more adult patients present with isolates resistant to these traditional options.
The polymyxins are a class of cyclic peptide antibiotics that exert bactericidal activity through binding to the lipopolysaccharide component of gram-negative bacterial membranes and include colistin and polymyxin B (PMB). In recent years, there is growing evidence of increased rates of acute kidney injury associated with colistin in critically ill patients. Additionally, population pharmacokinetic (PK) studies suggest that fixed drug dosing may yield an improved therapeutic index over the traditional weight-based dosing of this agent. Thus there is growing interest in use of PMB as an alternative in CF acute exacerbations but the optimal dosage regimen is not known.
This is a single-center, open-label, non-interventional study to characterize the pharmacokinetics and safety of fixed-dose PMB in adult patients with CF by measuring serum concentrations in patients receiving IV therapy as a part of routine care. This study will help to validate existing population PK models and allow for adjustment of patient specific covariates (i.e. weight, renal function) unique to adult patients with CF. The study will also monitor for nephrotoxicity and neurotoxicity to determine if PMB has an acceptable margin of safety in this patient population. This investigation is the first to prospectively validate the pharmacokinetics and toxicities of fixed-dose PMB in CF and will guide optimal use of this compound in the management of acute pulmonary exacerbations.
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Adults ≥ 18 years of age.
- Diagnosis of CF.
- Receiving polymyxin B in the course of routine care.
Exclusion Criteria:
- Evidence of acute kidney injury during the 48 hours prior to and following initiation of PMB therapy.
- Extracorporeal organ support (including ECMO, iHD, and CRRT).
- Pregnant or breastfeeding women.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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Patients with CF lung disease receiving Polymyxin B (PMB)
Participants receiving polymyxcin B as part of standard of care treatment for CF exacerbation will have blood drawn measure blood concentrations of PMB
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Blood samples will be collected from enrolled patients at 5 time points during a single dosing interval:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Polymyxin B compartmental population pharmacokinetics model
Time Frame: From immediately prior to a dose of therapy through 8 hours after therapy, approximately 8 hours
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The population pharmacokinetics of polymyxin B will be modeled based on the observed polymyxin B1 and B2 concentrations in plasma from enrolled patients who receive at least 1 dose of polymyxin B
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From immediately prior to a dose of therapy through 8 hours after therapy, approximately 8 hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Acute kidney injury
Time Frame: From 48 hours after first dose through 48 hours after end of therapy, approximately 7-21 days depending on the length of the prescribed therapy
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Frequency of acute kidney injury occurring between 48 hours after initiation of polymyxin B and 48 hours after end of therapy
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From 48 hours after first dose through 48 hours after end of therapy, approximately 7-21 days depending on the length of the prescribed therapy
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Neurotoxicity
Time Frame: From initiation of first dose through end of therapy, approximately 7-21 days depending on the length of the prescribed therapy
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Frequency of neurotoxicities occurring during polymyxin B treatment as documented by the primary clinical team
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From initiation of first dose through end of therapy, approximately 7-21 days depending on the length of the prescribed therapy
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Change in forced expiratory volume in one second (FEV1)
Time Frame: FEV1 at baseline to 7 days post treatment, approximately 14-90 days in total
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After completion of polymyxin B therapy as documented by the primary clinical team
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FEV1 at baseline to 7 days post treatment, approximately 14-90 days in total
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Non-reponse to therapy
Time Frame: From initiation of therapy through end of therapy, approximately 7-21 days depending on prescribed length of therapy
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Proportion of subjects requiring a change to antibiotic therapy due to non-response as documented by the primary clinical team
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From initiation of therapy through end of therapy, approximately 7-21 days depending on prescribed length of therapy
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Shijing Jia, University of Michigan
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HUM00150013
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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