Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: AZLI 75 mg two times a day (BID)/three times a day (TID); Placebo two times a day (BID)/three times a day (TID)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 211.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No
Keywords: Cystic Fibrosis; Pseudomonas aeruginosa; Pulmonary Cystic Fibrosis

Summary:

      The purpose of this study was to evaluate the safety and efficacy of aztreonam for inhalation
      solution (AZLI) in patients with cystic fibrosis (CF) and lung infection due to Pseudomonas
      aeruginosa (PA).
    

Eligibility criteria:

        Inclusion Criteria:

          -  CF as diagnosed by:

               1. Documented sweat chloride greater than or equal to 60 mEq/L by quantitative
                  pilocarpine iontophoresis test; or

               2. Two well-characterized genetic mutations in the cystic fibrosis transmembrane
                  conductance regulator (CFTR) gene; or

               3. Abnormal nasal potential difference with accompanying symptoms characteristic of
                  CF.

          -  PA present in expectorated sputum or throat swab culture at Screening.

          -  Participants must have received three or more courses of TIS within the previous 12
             months.

          -  Participants on chronic azithromycin must have had no change in regimen in the
             previous 3 months and must have had a need for TIS and/or additional antipseudomonal
             therapy since initiation of azithromycin.

          -  Forced expiratory volume in 1 second (FEV1) between (and including) 25% and 75%
             predicted at Screening.

          -  Ability to perform reproducible pulmonary function tests.

          -  Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at
             Screening.

        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 culture swab yielding Burkholderia cepacia in the past 2
             years.

          -  History of daily continuous oxygen supplementation or requirement for more than 2
             liters/minute at night.

          -  Administration of any investigational drug or device within 28 days of Screening
             (Visit 1) or within 6 half-lives of the investigational drug (whichever was longer).

          -  Known local or systemic hypersensitivity to monobactam antibiotics.

          -  Inability to tolerate inhalation of a short acting Beta-2 agonist.

          -  Changes in antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid
             medications within 7 days before Screening or between Screening and the next visit.

          -  Changes in physiotherapy technique or schedule within 7 days before Screening or
             between Screening and the next visit.

          -  History of lung transplantation.

          -  A chest X-ray indicating abnormal findings at Screening or within the previous 90
             days.

          -  Abnormal renal or hepatic function or serum chemistry at Screening (aspartate
             aminotransferase [AST], alanine aminotransferase [ALT] greater than 5 times the upper
             limit of normal range; Creatinine greater than 2 times the upper limit of normal
             range).

          -  Positive pregnancy test at Screening.

          -  Female of childbearing potential who was lactating or in the opinion of the
             investigator was not practicing acceptable birth control.

          -  Any serious or active medical or psychiatric illness, which in the opinion of the
             investigator would have interfered with participant treatment, assessment, or
             compliance with the protocol.