Dose-finding Study to Assess the Efficacy, Safety and Tolerability of Tobramycin Inhalation Powder in Patients With Non-Cystic Fibrosis Bronchiectasis and Pulmonary P. Aeruginosa Infection
Condition: Non-cystic Fibrosis Bronchiectasis
MeSH terms: Infections; Respiratory Aspiration; Bronchiectasis; Fibrosis
Intervention: TIP; TIP and placebo; Placebo
Intervention description: TIP dose regimen; TIP and inhaled placebo dose regimen; Inhaled placebo dose regimen
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 107.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Inhaled tobramycin; tobramycin inhalation powder; bronchiectasis; pulmonary Pseudomonas aeruginosa infection; dose-finding study

Summary:

      The purpose of this study was to support the selection of a safe and tolerable tobramycin
      inhalation powder (TIP) dose, and regimen that exhibits effective bacterial reduction of P.
      aeruginosa in non-cystic fibrosis bronchiectasis (BE) patients with P. aeruginosa
      colonization.
    

Eligibility criteria:

        Key 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 intravenous 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.

        Key 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.

          -  Patients with active pulmonary tuberculosis.

          -  Patients currently receiving treatment for nontuberculous mycobacterial (NTM)
             pulmonary disease.

          -  Patients who are regularly receiving inhaled anti-pseudomonal antibiotic (during the
             study inhaled anti-pseudomonal antibiotics are not allowed other than the study drug).