non-cystic fibrosis bronchiectasis
Conditions
Interventions
If you qualify for the study, you will enter the study treatment period where
you will be assigned to one of the 9 treatment groups by chance by using a
computer. There is about a 1 in 5 chance of r
bronchiectasis
dose-finding study
pulmonary Pseudomonas aeruginosa infection
Sponsors
Novartis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: * Written informed consent must be obtained before any assessment is performed. * Male and female patients of * 18 years of age at screening (Visit 1). * Proven diagnosis of non-CF BE as documented by computed tomography or high-resolution computed tomography * At least 2 or more exacerbations treated with oral antibiotics OR 1 or more exacerbation requiring parenteral antibiotic treatment within 12 months prior to screening. * FEV1 * 30% predicted at screening (Visit 1). * P. aeruginosa, must be documented in a respiratory sample at least 1 time within 12 months and also present in the expectorated sputum culture at Visit 1.
Exclusion criteria
Exclusion criteria: * Patients with a history of cystic fibrosis. * Patients with a primary diagnosis of bronchial asthma. * Patients with a primary diagnosis of COPD associated with at least a 20 pack year smoking history. * Any significant medical condition that is either recently diagnosed or was not stable during the last 3 months, other than pulmonary exacerbations, and that in the opinion of the investigator makes participation in the trial against the patients* best interests. * Clinically significant (in the opinion of the investigator) hearing loss that interferes with patients* daily activities (such as normal conversations) or chronic tinnitus. Patients with a past history of clinically significant hearing loss in the opinion of the investigator may be eligible only if their hearing threshold at screening audiometry is 25dB or lower at frequencies 0.5-4 kHz. The use of a hearing device is reflective of a clinically significant hearing loss; hence patients using hearing aids at screening are not eligible (revised per amendment 02). * Patients with active pulmonary tuberculosis. * Patients currently receiving treatment for nontuberculous mycobacterial (NTM) pulmonary disease. * Patients who are regularly receiving inhaled anti-pseudomonal antibiotic within 28 days prior to study drug administration (Visit 101).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy objective is to evaluate the effect of different daily doses of TIP on the change in P. aeruginosa bacterial load in sputum as assessed by the change in colony forming units (CFUs) from baseline to Day 29 of treatment, each compared to placebo. The comparisons of different TIP daily doses (combining TIP continuous or TIP/placebo cyclical regimens within a cohort) versus placebo will be evaluated by testing the following null hypothesis (H0) versus the alternative hypothesis (Ha): H0: TIP treatment group is equal to placebo group in bacterial load in sputum at Day 29 Ha: TIP treatment group is not equal to placebo group in bacterial load in sputum at Day 29 The primary efficacy endpoint will be analyzed using the analysis of covariance (ANCOVA) model. The model will contain treatment, cohort, baseline CFU, and baseline macrolide use. Pairwise comparisons of TIP dosing groups will be conducted versus placebo. To control the family-wise type-I error rate (three dose levels vs. placebo) at the two-sided 5% significance level, the step-wise Dunnett procedure will be used. The estimated adjusted treatment difference (TIP * placebo) will be displayed along with the associated standard error, 2-sided 95% confidence interval (CI), and p-value (2-sided). | — |
Countries
Belgium, France, Germany, Ireland, Italy, Netherlands, Spain, Switzerland, United Kingdom
Outcome results
None listed