Aztreonam for Inhalation Solution vs Tobramycin Inhalation Solution in Patients With Cystic Fibrosis & Pseudomonas Aeruginosa
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Respiratory Aspiration; Fibrosis
Intervention: Aztreonam for Inhalation Solution (AZLI); Tobramycin Inhalation Solution (TIS)
Intervention description: Aztreonam for inhalation solution (75 mg) was administered 3 times a day (TID) for 28 days for each treatment cycle via the PARI eFlow electronic nebulizer.; Tobramycin inhalation solution (300 mg) was administered 2 times a day (BID) for 28 days for each treatment cycle via the PARI LC Plus nebulizer with compressor or via another nebulizer compatible with country-specified labeling.
Intervention MeSH terms: Anti-Bacterial Agents; Tobramycin; Aztreonam; Antibiotics, Antitubercular; Pharmaceutical Solutions
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 274.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No
Keywords: aztreonam lysine; tobramycin inhalation solution; tobramycin nebuliser solution; cystic fibrosis; pseudomonas aeruginosa; lung infection; CFQ-R; inhaled antibiotic

Summary:

      The purpose of this study was to assess the comparative safety and effectiveness of aztreonam
      for inhalation solution versus tobramycin inhalation solution in adult and pediatric patients
      with cystic fibrosis (CF) and pulmonary Pseudomonas aeruginosa (PA) infection.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females aged 6 years and older

          -  Subjects with CF as diagnosed by one of the following: documented sweat chloride >= 60
             mEq/L by quantitative pilocarpine iontophoresis test, or documented sweat sodium >= 60
             mmol/L, or 2 well characterized genetic mutations in the Cystic Fibrosis Transmembrane
             Conductance Regulator (CFTR) gene, or abnormal nasal potential difference with
             accompanying symptoms characteristic of CF

          -  Documented PA in an expectorated sputum or throat swab culture within 3 months prior
             to Visit 1 or at Visit 1

          -  Subjects must be able to provide written informed consent/assent prior to any study
             related procedures; parent/guardian must be able to give written informed consent as
             necessary prior to any study related procedure

          -  Subjects must have received previous treatment with aerosolized antibiotics without
             demonstration of drug intolerance

          -  FEV1 <= 75% predicted at Visit 1

          -  Ability to perform reproducible pulmonary function tests

          -  Chest radiograph at Visit 1 without significant acute findings (eg, infiltrates [lobar
             or diffuse interstitial], pleural effusion, pneumothorax); or chest radiograph or
             magnetic resonance image (MRI) obtained within the 180 days prior to Visit 1 without
             acute findings and no significant intercurrent illness; chronic, stable findings (eg,
             chronic scarring or atelectasis) are allowed

        Exclusion Criteria:

          -  Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg
             prednisone a day or 20 mg prednisone every other day

          -  History of sputum or throat swab culture yielding B. cepacia in the previous 2 years

          -  Current requirement for daily continuous oxygen supplementation or requirement for
             more than 2 L/minute at night

          -  Administration of any investigational drug or device within 28 days of Visit 1 or
             within 6 half-lives of the investigational drug (whichever is longer)

          -  Known local or systemic hypersensitivity to monobactam antibiotics

          -  Known allergies/intolerance to tobramycin

          -  Inability to tolerate inhalation of a short acting beta agonist

          -  Changes in or initiation of chronic azithromycin treatment within 28 days prior to
             Visit 1

          -  Administration of antipseudomonal antibiotics by inhalation, intravenous or oral
             routes within the 14 days prior to Randomization/Visit 2

          -  Changes in antimicrobial, bronchodilator (BD), dornase alfa, or corticosteroid
             medications within 7 days prior to Visit 1

          -  Changes in physiotherapy technique or schedule within 7 days prior to Visit 1

          -  History of lung transplantation

          -  Abnormal renal or hepatic function or serum chemistry at Visit 1, defined as aspartate
             aminotransferase (AST), alanine aminotransferase (ALT) > 5 times upper limit of normal
             range (ULN) or creatinine > 2 times ULN

          -  Positive pregnancy test at Visit 1; all women of childbearing potential will be tested

          -  Female of childbearing potential who is lactating or is not (in the opinion of the
             investigator) practicing an acceptable method of birth control; female subjects who
             utilize hormonal contraceptives as one of their birth control methods must have used
             the same method for at least 3 months before study dosing

          -  Any serious or active medical or psychiatric illness, which in the opinion of the
             investigator, would interfere with patient treatment, assessment, or compliance with
             the protocol