Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa
Condition: Cystic Fibrosis; Lung Infection; Pseudomonas Aeruginosa
MeSH terms: Pseudomonas Infections; Cystic Fibrosis; Lung Diseases; Fibrosis
Intervention: AZLI 75 mg three times daily (TID); Placebo three times daily (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: 160.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No
Keywords: cystic fibrosis; pseudomonas aeruginosa; lung infection; CFQ-R; inhaled antibiotic; aztreonam lysine

Summary:

      The purpose of this study was to evaluate the safety and efficacy of a 28-day course of
      aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis (CF), mild lung
      disease (forced expiratory volume in 1 second [FEV1] >75% predicted, and Pseudomonas
      aeruginosa (PA) infection.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants ≥ 6 years of age

          -  Documentation of CF diagnosis as evidenced by one or more clinical features consistent
             with the CF phenotype and one or more of the following criteria:

               -  Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test

               -  Two well characterized mutations in the cystic fibrosis transmembrane conductance
                  regulator (CFTR) gene

               -  Abnormal nasal potential difference

          -  PA present in expectorated sputum or throat swab culture at Visit 1 OR documented PA
             in 2 expectorated sputum or throat swab cultures within the 12 months prior to Visit 1
             (one of the previous PA positive cultures must have been no more than 3 months prior
             to Visit 1)

          -  FEV1 > 75% predicted at Visit 1

          -  Participants must have exhibited two or more of the following chronic and/or
             intermittent CF symptoms, for a minimum of 28 days prior to randomization and with no
             worsening of symptoms within 7 days prior to randomization:

               -  Chest congestion

               -  Daily cough

               -  Productive cough

               -  Wheezing

               -  Trouble breathing

               -  Nocturnal wakening due to coughing

          -  Participants (and parent/guardian as required) had to be able to provide written
             informed consent/assent prior to any study related procedures

          -  Females of childbearing potential had to have a negative urine pregnancy test at Visit
             1

          -  Ability to perform reproducible pulmonary function tests

          -  In the opinion of the Investigator, the participant did not require immediate
             antipseudomonal antibiotic intervention to treat an impending exacerbation, and the
             participant's condition was stable enough to enroll in the study

        Exclusion Criteria:

          -  Administration of any investigational drug or device within 28 days prior to Visit 1
             or within 6 half-lives of the investigational drug (whichever was longer)

          -  Administration of any IV, oral, or inhaled antipseudomonal antibiotic within 28 days
             prior to Visit 1

          -  Known local or systemic hypersensitivity to monobactam antibiotics

          -  Inability to tolerate short-acting bronchodilator (BD) use at least TID

          -  Changes in or initiation of chronic azithromycin treatment within 28 days prior to
             Visit 1

          -  Changes in or initiation of chronic hypertonic saline treatment within 28 days prior
             to Visit 1

          -  Changes in or initiation of dornase alfa within 28 days prior to Visit 1

          -  Changes in antimicrobial, BD, 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

          -  History of participation (enrollment) in any prior clinical studies with AZLI

          -  A chest radiograph at Visit 1 (or within the previous 180 days of Visit 1), with
             abnormalities indicating a significant acute finding (e.g., lobar infiltrate and
             atelectasis, pneumothorax, or pleural effusion); a chest radiograph obtained and
             interpreted between Visits 1 and 2 was also acceptable for determining eligibility

          -  Positive urine pregnancy test at Visit 1; all women of childbearing potential were to
             be tested

          -  Females of childbearing potential who were lactating or were not (in the opinion of
             the investigator) practicing an acceptable method of birth control; female
             participants who utilized hormonal contraceptives as their birth control method must
             have used the same method for at least 3 months before study dosing

          -  Participant was being assessed at Visit 1 by the investigator for an acute change in
             respiratory symptoms

          -  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