Cystic Fibrosis with Pseudomoas aeuriginosa infection MedDRA version: 8.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung
Conditions
Interventions
Product Name: Tobramycin 100 PARI
Product Code: T100 PARI
Pharmaceutical Form: Inhalation vapour, solution
INN or Proposed INN: Tobramycin
Concentration unit: mg/ml milligram(s)/millilitre
Concentrati
Sponsors
PARI Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients older than 8 years of age. - Subjects with documented CF: Documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) or homozygosity for AF508 genetic mutation (or heterozygosity for two well characterized mutations) and two clinical findings consistent with CF. - Ability to perform reproducible spirometry. - Stable condition with no exacerbation requiring IV antibiotics or hospitalization within one months period prior to screening visit. - No change in FEV1 bigger than 20% from baseline within one month period prior to screening visit. - Documented P. aeruginosa presence in a sputum/throat culture within 6 months prior to screening or at least two consecutive positive P. aeruginosa cultures within one year. - FEV1 at least of 40% of predicted, based on gender, age and height. - Room air oximetry from at least 88% saturation. 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 an investigational drug within 30 days prior to study entry or during the trial. 2. Active drug and alcohol abuse. 3. Inability to handle the study inhalers or to inhale the test formulations. 4. Inability to adhere to the requirements of the protocol. 5. FEV1 lesst han 40% predicted. 6. Administration of any anti pseudomonas antibiotics by any route within 7 days prior to initial study drug administration, with the exception of macrolide, provided that these are taken as a maintenace therapy at least 6 weeks before entering the trial. 7. Severe respiratory infection within one month prior to screening, which requires hospital admission or treatment with intravenous antiobiotics 8. Positive urine pregnancy test. 9. Hemoptysis > 60 cc at any time within thirty days prior to study drug administration. 10. Known local or systemic hypersensitivity to aminoglycosides. 11. Serum creatinine = or greater than 1,2 mg/d, BUN = 20 mg/dl or greater, or an abnormal urine analysis defined as more than 1+ proteinuria in urinstix. 12.History of sputum culture or throat swab culture yielding B.cepacia in the previous 12 months and/or sputum or throat swab culture yielding B. cepacia at screening. 13. Presence of allergic bronchopulmonary aspergillosis (ABPA) as evidenced by positive cultures for aspergillosis, positive skin test and IgE>1000 IU. 14. Patients with right side heart failure. 15. Non-compliance with recommended pulmonary rehabilitation 16. Significant liver disease clinically diagnosed. 17. Patients with history of GI bleeding. 18. Patients with known or suspected neuromuscular dysfunction. 19. Patients with known or suspected auditory or vestibular dysfunction. 20. Women of childbearing potential and sexually active who are not already using a high effective method of contraception.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the bioavailability in the Tobramycin 100 PARI / eFlow treatment group compared to the TOBI® / PARI LC PLUS / PRONEB® ULTRA compressor treatment group. Both groups of patients will be treated during a period of 28 days, receiving the study medication twice a day. 1. Evaluation of serum and sputum levels of the new formulation Tobramycin 100 PARI containing 150 mg / 1.5 ml Tobramycin nebulized via eFlow®, compared with the registered TOBI® nebulized via PARI LC PLUS. Primary endpoint is plasma tobramycin levels at day 7. 2. Evaluation of safety data: safety of Tobramycin 100 PARI will be determined for 28 days treatment in 30 CF patients. The active control arm has 30 CF patients receiving TOBI standard therapy. Primary endpoint: Pharmacokinetics: serum Tobramycin levels at day 7 ;Primary end point(s): Pharmacokinetics: serum Tobramycin levels at day 7: trough level, peak level and area under the curve (AUC). ;Secondary Objective: - Sputum Tobramycin levels at days 1, 7 and 28, measured 10 minutes after end of inhalation. - Trough tobramycin plasma levels at days 1 and 28, measured before inhalation of study medication. Tolerability: - Bronchospasm: number and relative percentage of patients with bronchospasm (defined as a fall in FEV1 > 15% at 30 min after the end of inhalation) - Fall of FEV1 in percent from pre- to post treatment Safety endpoints: - Extreme cough or wheezing or onset of respiratory distress. - Frequency and severity of dyspnea. - Audiology: audiological alterations and signs of tinnitus will be recorded. - Proportion of subjects reporting advers events. - Proportion of subjects with laboratory test abnormalities. | — |
Countries
Germany
Outcome results
None listed