Chronic lung infection with Pseudomonas aeruginosa in cystic fibrosis patients MedDRA version: 18.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 18.0 Level: LLT Classification code 10021860 Term: Infection Pseudomonas aeruginosa System Organ Class: 100000004862
Conditions
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent and assent (as appropriate for minors) prior to the performance of any study-related procedure. 2. Confirmed diagnosis of CF by one or more of the following tests for CF (current or historic): a. quantitative pilocarpine iontophoresis sweat chloride test of greater than 60 mmol/L or 60 mEq/L b. genotype with 2 identifiable CF-causing mutations c. an abnormal nasal transepithelial potential difference characteristic of CF 3. Male and female patients 6 - 50 years of age at screening (Visit 1). 4. Patients with elevated LCI of = 7.5 at screening, confirmed by a central MBW specialist. 5. Patients with FEV1 of = 50% predicted at screening. 6. P. aeruginosa must be present in two sputum or deep cough throat swab cultures or bronchoalveolar lavage (BAL) (only for BAL, a threshold level of 103 CFU/mL is required) within 12 months prior to screening or in one culture within 12 months prior to screening and in the sputum or deep cough throat swab culture at screening. 7. Use of inhaled Tobramycin in a 28 days on / off regimen in the past 3 months before screening, as prescribed by the treating physician. 8. Clinically stable in the opinion of the investigator and likely to be able to participate in the study until the end of the study (Visit 5). Are the trial subjects under 18? yes Number of subjects for this age range: 17 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of sputum culture or deep cough throat swab (or BAL) culture yielding Burkholderia cenocepacia complex within 2 years prior to screening and / or sputum culture yielding B. cenocepacia complex at screening (Visit 1). 2. Hemoptysis more than 60 mL at any time within 30 days prior to screening (Visit 1). 3. History of hearing loss or chronic tinnitus. 4. Serum creatinine 2mg/dL or greater, BUN 40 mg/dL or greater, known local or systemic hypersensitivity to aminoglycosides. 5. Patients who are regularly receiving more than 1 class of inhaled anti-pseudomonal antibiotic during the study or in the past 56 days (8 weeks) prior to baseline visit (Visit 2). 6. Patients who have used oral or intravenous anti-pseudomonal antibiotics within 28 days prior to on-phase of study drug (Visit 2). These patients may be rescreened after 1 month following stop of i.v. treatment. 7. Change in dose, formulation or strength of the study drug in the past treatment cycle before screening. 8. Patients following onset or discontinuation of therapy with macrolides, chest physiotherapy, nebulized hypertonic saline, dornase alpha, long acting bronchodilators, inhaled steroids or inhaled mannitol during the study and within 56 days (8 weeks) prior to baseline visit (V2). 9. Use of loop diuretics within 7 days prior to first study medication administration (Visit 2). 10. Administration of any investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening (Visit 1). 11. Signs and symptoms of acute pulmonary disease, e.g. pneumonia, pneumothorax. 12. Body mass index less than 12 kg/m2. 13. History of malignancy of any organ system, treated or untreated, regardless of whether there is evidence of local recurrence or metastases. 14. Patients with known or suspected neuromuscular disorders, e. g. Parkinson´s disease, Myasthenia gravis. 15. Patients or caregivers who are considered potentially unreliable or considered unlikely to be compliant within the trial. 16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL). 17. Women who are menstruating and capable of becoming pregnant* and either not practicing a medically approved method of contraception (Pearl Index 40 mIU/mL or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy **examples of particularly reliable methods with Pearl Index (PI) <1, according to guidelines of Deutsche Gesellschaft für Gynäkologie und Geburtshilfe: • hormonal oral contraception (Combination of estrogen and gestagen, PI=0.1-0.9) • hormonal vaginal ring (combination of estrogen and gestagen, PI=0.65 uncorr.; 0.4 corr.) • hormonal transdermal patch (combination of estrogen and gestagen PI= 0.72 uncorr.; 0.9 corr.) • Estrogen-free ovulation inhibitors (containing desogestrel (PI=0.14) • Implanted hormones containing etonogestrel (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the change of LCI after 4 weeks following onset of study drug inhalation versus Baseline;Secondary Objective: To assess: • Change of FEV1 after 4 weeks following onset of study drug inhalation versus Baseline. • Change in CFU after 4 weeks following onset of study drug inhalation versus Baseline • Change of LCI after 1 week following onset of study drug inhalation versus Baseline. • Change of LCI, FEV1 and CFU between week 4 (end of Study drug inhalation in the current treatment cycle) and week 8 (prior to start of Study drug inhalation in the following treatment cycle). • Correlation between the changes of LCI, FEV1 and CFU after 1 week, 4 weeks, and 8 weeks versus Baseline, respectively. ;Primary end point(s): Change of LCI after 4 weeks following onset of study drug inhalation versus Baseline;Timepoint(s) of evaluation of this end point: 4 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Change of FEV1 2 - Change in CFU 3 - Change of LCI 4 - Change of LCI, FEV1 and CFU 5 - Correlation between the changes of LCI, FEV1 and CFU ;Timepoint(s) of evaluation of this end point: 1- after 4 weeks following onset of study drug inhalation versus Baseline 2- after 4 weeks following onset of study drug inhalation versus Baseline 3- after 1 week following onset of study drug inhalation versus Baseline 4- between week 4 (end of Study drug inhalation in the current treatment cycle) and week 8 (prior to start of Study drug inhalation in the following treatment cycle). 5- after 1 week, 4 weeks, and 8 weeks versus Baseline, respectively. | — |
Countries
Germany
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed