Cystic fibrosis with bronchopulmonary chronic Pseudomonas aeruginosa infection MedDRA version: 12.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung
Conditions
Interventions
Product Name: Tobramycin
Product Code: T100
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: Tobramycin
CAS Number: 32986-56-4
Other descriptive name: Tobramycinum
Concentration u
Sponsors
PARI Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed by patient (or appropriate legal representative) the written informed consent including data protection agreement after the nature of the study has been fully explained prior to any screening procedure. 2. Patient is a male or female and at least 4 years of age at the time of screening. 3. Patient’s diagnosis of cystic fibrosis (CF) was confirmed by · one or more specific clinical features consistent with CF and · elevated chloride concentration in the sweat = 60 mEq/l (by quantitative pilocarpine iontophoresis test - QPIT) and/or · presence of disease-associated CF transmembrane conductance regulator (CFTR) mutations in both alleles. 4. Patient has adequate pulmonary function at screening defined as: · FEV1 between at least 25% and less or equal to 85% of normal predicted values for age, sex and height based on Knudson criteria and · peripheral artery haemoglobin oxygen saturation (SaO2) of at least 88% at rest measured by pulse oximetry on room air. 5. Patient has a positive culture for PA at screening (Visit 1): patient should have PA isolated from sputum only if patient do not have a known history of positive PA culture within the last 2 months. 6. Patient is clinically stable at screening (no change in FEV1 > 20% within one month prior to screening Visit). 7. Patient is able to comply with all protocol requirements (e.g. able to produce sputum and perform pulmonary function tests). 8. Sexually active women of childbearing potential and sexually active men will use a highly effective method of contraception throughout the IMP treatment period. (See Appendix 1). 9. Females of childbearing potential have a negative serum pregnancy test (within 7 days before Visit 2/randomisation). Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Use of investigational medications within 30 days before study entry or during the trial. 2. Inability to handle the study inhalers to inhale the test preparations. 3. Patient has a known local or systemic hypersensitivity or adverse reaction to inhaled aminoglycosides or systemic aminoglycosides 4. Administration of anti-pseudomonas aminoglycoside antibiotics are not allowed within 30 days before first administration of IMP. Macrolide are permitted, provided that they are taken as a maintenance therapy for at least 6 weeks before entering the trial. Other antibiotics are not allowed within 7 days before first administration of IMP. (For details see Appendix 2). 5. Patient with haemoptysis at any time within 4 weeks prior to screening (Visit 1) 6. FEV1 1.2 mg/dl or BUN 20 mg/dl or proteinuria of grade 2+ or greater. 11. Significant liver disease (> 2x upper standard limits and no thrombocytopenia or clinical active disease). 12. Patients with auditory or/and vestibular dysfunctions 13. Patient has a history of lung transplantation. 14. Patient has a co-existing medical condition or abnormality that would compromise the participant's safety or the quality of the study data, in the opinion of the investigator. 15. Active drug and alcohol abuse or psychiatric disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary endpoint: · To determine the bioequivalence of the new Tobramycin PARI formulation to TOBI by evaluating the plasma tobramycin concentrations measured as mean plasma AUC0-12h of the new T100 formulation nebulised via eFlow®, compared with the registered TOBI® nebulised via PARI LC PLUS after 4 weeks of each treatment phase. Full pharmacokinetic tobramycin level in plasma will be measured at visit 3 and 5. The acceptance level for the 90% confidence interval of mean plasma tobramycin AUC0-12h is 80-125%.;Secondary Objective: Secondary endpoints: · Mean plasma tobramycin peak concentration Cmaxplasma in after 4 weeks of each treatment phase. The acceptance level for the 90% confidence interval of peak tobramycin Cmaxplasma is 70-133% · Mean sputum tobramycin peak concentrations ( sputum max C ) after 4 weeks of each treatment phase. The statistical evaluation of this endpoint will be solely descriptive. Pharmacokinetics will be measured at visit 3 and visit 5.;Primary end point(s): Comparison of mean plasma tobramycin AUC0-12h of T100 170 mg nebulised via eFlow® and the registered TOBI® 300 mg nebulised via PARI LC PLUS. [tobramycin AUC0-12h ?visit5 – visit3]. The acceptance level for the 90% confidence interval of mean plasma tobramycin AUC0-12h is 80-125%. | — |
Countries
Poland
Outcome results
None listed