Pharmacokinetic Study of Bramitob® Administered for Inhalation by PARI eFlow® vs PARI LC® PLUS Nebulizer

Study Overview
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Brief Summary
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The purpose of this study is to assess pharmacokinetic and safety comparability of Bramitob® when administered for inhalation by using PARI eFlow® rapid electronic nebulizer vs PARI LC® PLUS nebulizer in Cystic Fibrosis Patients infected with Pseudomonas Aeruginosa

Official Title
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PHARMACOKINETIC STUDY OF BRAMITOB® ADMINISTERED FOR INHALATION BY PARI eFLOW® RAPID ELECTRONIC NEBULIZER VS PARI LC® PLUS NEBULIZER COUPLED WITH THE PARI TURBO BOY® N COMPRESSOR IN CYSTIC FIBROSIS PATIENTS INFECTED WITH PSEUDOMONAS AERUGINOSA

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Bramitob® administered by PARI LC® PLUS nebulizer
* Drug: Bramitob® administered by PARI eFlow® rapid electronic nebulizer


Participation Criteria
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Eligibility Criteria
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Main inclusion Criteria: Patients of either sex aged ≥ 18 years; Clinical diagnosis of cystic fibrosis (patients registered in the National Registry of cystic fibrosis or other documents, if applicable, depending on country legislation); Positive response (sweat chloride concentration ≥ 60 mmol/l) in the standard sweat test documented in the clinical records or sweat chloride concentration ≥ 40 mmol/l and at least two gene mutations consistent with CF documented in the clinical records; Chronic colonization of Pseudomonas aeruginosa FEV1 ≥ 35% of the predicted normal value calculated according to the recommendation of the Official Statement of the European Respiratory Society and American Thoracic Society Main exclusion Criteria: Evidence of impaired renal function (serum creatinine level ≥ 1.5 mg/dl); Evidence of impaired auditory function (auditory threshold in either ear above 20 dB at frequencies between 250 and 8000Hz); Sputum culture containing Burkholderia cepacia; Received loop diuretics within 7 days before study drug administration;

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PARI LC® PLUS nebulizer<br> | Drug: Bramitob® administered by PARI LC® PLUS nebulizer<br>* (tobramycin 300mg /4mL) solution administered by inhalation twice daily for 28 days<br>* Other names: Bramitob®, Tobrineb®, Actitob®;|
| Active Comparator: PARI eFlow® rapid electronic nebulizer<br> | Drug: Bramitob® administered by PARI eFlow® rapid electronic nebulizer<br>* (tobramycin 300mg /4mL) solution administered by inhalation twice daily for 28 days<br>* Other names: Bramitob®, Tobrineb®,Actitob®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma tobramycin pharmacokinetic parameters (Cmax and AUC0-t) after twice daily inhalation of Bramitob® using PARI eFlow® nebulizer vs PARI LC® PLUS nebulizer |  | on day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma tobramycin pharmacokinetic parameters (Cmax, tmax and AUC0-t) after inhalation of Bramitob® using PARI eFlow® nebulizer vs PARI LC® PLUS nebulizer |  | on day 1 | 
| Sputum tobramycin pharmacokinetic parameters (Cmax, tmax and AUC0-t) after inhalation of Bramitob® using PARI eFlow® nebulizer vs PARI LC® PLUS nebulizer |  | on day 1 and on day 28 | 
| Accumulation of tobramycin in plasma and sputum after repeated doses calculated as the ratio: AUC0-t DAY 28 / AUC0-t DAY 1 and Cmax DAY 28 / Cmax DAY 1 |  | day 1 - day 28 | 
| Safety assessed by adverse events, adverse drug reactions, incidence of bronchospasm, laboratory parameters, physical examination, body weight, vital signs results |  | day1-day28 | 
| Number of patients with minimum plasma tobramycin levels Cmin > 2mcg/mL and maximum plasma tobramycin levels Cmax > 12 mcg/mL |  | on day 28 | 
| Time necessary for the nebulization of the dose |  | on day 1 and on day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic fibrosis, tobramycin,nebulizer, PK