Pharmacokinetic Bioequivalence Study of Nebcinal® 150mg/3ml Administered by Aeroneb® Idehaler® Versus Tobi® 300mg/5ml Administered by Pari LC Plus® /Pulmoaid® in Patients With Cystic Fibrosis

Study Overview
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Brief Summary
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Cystic fibrosis (CF) is a genetic disease characterized by mutations in CFTR (Cystic Fibrosis Transmembrane conductance Regulator) gene. Mortality and morbidity are mostly related to the respiratory affection which appears early in neonates. The constant improvement in symptomatic treatments and care strategies allowed CF patients' life expectancy to be increased over the last decades. Vital prognostic is related to bronchopulmonary infections. 39% of CF patients under 18 years old and 70% of adult CF patients are chronically infected by Pseudomonas aeruginosa. Elevated concentrations of tobramycin in broncho secretions, about 1000 times the MIC, is obtained by inhaled administration of tobramycin and is active against in-vitro resistant Pseudomonas aeruginosa. Study hypotheses : Regarding literature data and in-vitro studies, the administration of Nebcinal® 150mg/3ml administered twice a day by Aeroneb® Idehaler® pocket® would deliver the same quantity of antibiotic in lung and plasma as Tobi® 300mg/5ml administered twice a day by Pari® LC Plus® in children and adult patients with CF. Primary objective : To compare plasma concentrations after inhalation of Nebcinal® 150mg/3ml administered by Aeroneb® Idehaler pocket® and Tobi® 300 mg/5ml administered by Pari LC Plus®

Official Title
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Pharmacokinetic Bioequivalence Study of Nebcinal® 150mg/3ml Administered by Aeroneb® Idehaler® Versus Tobi® 300mg/5ml Administered by Pari LC Plus® /Pulmoaide® in Patients With Cystic Fibrosis.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Tobramycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults and children aged 6 years old and more Male or female Patients with cystic fibrosis (positive sudoral test, Cl > 60 mmol/L) Followed in a CRCM (CF care centre) FEV1 ≥40% Informed consent collected from adults or parents or legal guardians and children. Affiliation to the National Health Insurance program (Sécurité sociale). Exclusion Criteria: renal insufficiency defined by a creatinine clearance level superior to 2 mg/dl recent pneumothorax, emphysema, punction or recent pleural biopsy, recent haemoptysis superior to 60 ml within 30 days prior to randomization Acute pulmonary exacerbation pathology, according to conference of consensus (2002), evaluated by : Cough increase Sputum increase Decrease in tolerance to effort Loss of weight, lack of appetite Deterioration of respiratory function Medical history of intolerance, toxicity or allergy to tobramycin, hypersensitivity to aminoside

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| Other: Arm A<br>experimental treatment (Nebcinal/Aeroneb Idehaler pocket) - 6day-wash out period - standard treatment (Tobi/Pari LC Plus) | Drug: Tobramycin<br> <br> |
| Other: Arm B<br>standard treatment (Tobi/Pari LC Plus) - 6day-wash out period - experimental treatment (Nebcinal/Aeroneb Idehaler) | Drug: Tobramycin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of tobramycin from 0 to 8h after administration |  | from 0 to 8h after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sputum of tobramycin concentrations |  | from 0 to 8 hours after administration | 
| Safety of Nebcinal® 150mg/3ml administered by Aeroneb® Idehaler pocket®; |  | 15 days | 
| Time of nebulization of Nebcinal® 150mg/3ml administered by Aeroneb® Idehaler pocket® |  | during nebulization | 
| Satisfaction of Nebcinal® 150mg/3ml administered by Aeroneb® Idehaler pocket® |  | after administration of the drug, in average 20 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetic, sputum, cystic fibrosis, bioequivalence, plasma