Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis

Study Overview
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Brief Summary
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The purpose of this study is to determine the pharmacokinetics and safety of inhaled vancomycin in patients with cystic fibrosis.

Detailed Description
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The prevalence of methicillin resistant Staphylococcus aureus (MRSA) respiratory infection in patients with cystic fibrosis has increased dramatically over the last decade. Epidemiologic evidence suggests that persistent infection with MRSA may result in an increased rate of decline in FEV1 and shortened survival. Treatment of MRSA is a top priority. Inhaled antibiotics offer the advantage of high concentrations of antibiotic at the site of infection (the airway) while minimizing systemic side effects. Vancomycin is a glycopeptide antibiotic that has activity against MRSA. Anecdotal and retrospective peer-reviewed studies have demonstrated that inhaled vancomycin is safe and potentially effective in patients with cystic fibrosis and MRSA airway infection. Data evaluating the pharmacokinetics of vancomycin in sputum are needed before pursuing treatment trials.

Official Title
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Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis

Conditions
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Cystic Fibrosis, Methicillin-resistant Staphylococcus Aureus

Intervention / Treatment
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* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age. Confirmed diagnosis of CF based on the following criteria: positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF or abnormal NPD, and one or more clinical features consistent with the CF phenotype. Chronic sputum producer able to spontaneously produce sputum FEV1 > 40% of predicted normal for age, gender, and height Previous use of any inhaled antibiotics within the last year Ability to provide written informed consent Ability to adhere to the protocol Exclusion Criteria: Use of inhaled or intravenous vancomycin within two weeks of the study visit Known history of intolerance to inhaled vancomycin or inhaled albuterol. Known history of hypersensitivity to vancomycin or other glycopeptide antibiotics History of sputum culture with Burkholderia cepacia complex in the last two years. Pregnancy Woman who are lactating and not willing to stop nursing on the day of the study visit and the subsequent 48 hours. Current use of oral corticosteroids in doses exceeding the equivalent of 10mg of prednisone a day or 20mg of prednisone every other day. Patients not willing to hold other inhaled antibiotics (for example TOBI, Cayston, or Colistin) for at least 2 days prior to the study visit. Patients not willing to hold loop diuretics (i.e. furosemide, torsemide, ethacrynic acid) on the morning of the study visit. History of ABPA or reactive airways disease that has required treatment within the last year. Creatinine greater than 2.0 mg/dL within the last year. Oxygen saturation ≤ 92% on room air. History of patient reported hearing loss Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patient treatment, assessment, or adherence to the protocol. History of or listed for solid organ or hematological transplantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vancomycin for Inhalation<br>250 mg vancomycin in 5cc sterile water will be inhaled once. Patients will use a Pari Sprint nebulizer and Pari Vios compressor as the delivery system. | Drug: Vancomycin<br>* 250 mg vancomycin in 5cc sterile water will be inhaled once. Patients will use a Pari Sprint nebulizer and Pari Vios compressor as the delivery system.<br>* Other names: Aerosolized Vancomycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under Curve (AUC) | Pharmacokinetic analysis will be performed with non-compartmental methods. The area under the curve for sputum vancomycin will be determined. | Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1% Predicted | Change in FEV1% predicted from baseline to 30 minutes after completion of inhaled vancomycin | 30 minutes | 
| Change in Patient Symptoms | Patient's respiratory symptoms and potential side effects from inhaling vancomycin will be queried using a questionnaire prior to inhaling vancomycin, at 15 ±10 minutes, and 4 ± 1 hour after completing inhaled vancomycin. | 6 hours | 
| Change in Sputum Cell Counts | Change in sputum cell counts (i.e. eosinophils) between baseline and six hours after completion of inhaled vancomycin. | 6 hours | 
| Serum Vancomycin Peak Concentration | Serum vancomycin peak concentration 60 minutes after completion of inhaled vancomycin. | 60 minutes | 
| Oxygen Saturation | Continuous oxygen saturation monitoring to be continued throughout vancomycin inhalation and for 5 minutes after inhalation | 5 minutes | 
| Adverse Events | Information regarding occurrence of adverse events will be captured throughout the study. Duration (start and stop times), severity/grade, outcome, treatment and relation to study medication will be recorded | 6 hours | 
| Maximum Concentration | Pharmacokinetic analysis will be performed with non-compartmental methods. The maximum concentration of sputum vancomycin will be determined. | Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin | 
| Time to Peak Concentration | Pharmacokinetic analysis will be performed with non-compartmental methods. The time to peak concentration for sputum vancomycin will be determined. | Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vancomycin, Inhalation, Nebulization, Pharmacokinetics