Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysine For Inhalation in Patients With Cystic Fibrosis, Mild Lung Disease, and P. Aeruginosa (AIR-CF4)
Brief 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.


Options:
A: 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
B: Inclusion Criteria:

* Diagnosis of CF, as determined by the 1997 CF Consensus Conference criteria: sweat chloride level greater than 60 milliequivalent/liter (mEq/L) by quantitative pilocarpine iontophoresis; or a genotype with two identifiable mutations consistent with CF; or an abnormal nasal transepithelial potential difference and one or more clinical features consistent with CF
* For participants greater than 15 months of age: documented new onset of positive oropharyngeal, sputum, or lower respiratory tract culture for PA within 6 months of study entry, defined as either: 1) first lifetime documented PA positive culture; or 2) PA recovered after at least a 2-year history of PA negative respiratory cultures (at least one culture per year)
* For participants 12-15 months of age: at least one documented positive oropharyngeal, sputum, or lower respiratory tract culture for PA since birth or CF diagnosis
* Clinically stable with no evidence of any significant respiratory symptoms or chest radiograph findings at screening that would require administration of intravenous anti-pseudomonal antibiotics, oxygen supplementation, or hospitalization

Exclusion Criteria:

* History of aminoglycoside hypersensitivity or adverse reaction to inhaled aminoglycoside
* History of hypersensitivity or adverse reaction to ciprofloxacin or other fluoroquinolone medications
* History of persistent, unresolved hearing loss documented by audiometric testing on at least two occasions and not associated with middle ear disease or an abnormal tympanogram
* Abnormal kidney function at study entry (defined as a serum creatinine level greater than 1.5 times the upper limit of normal for participant's age)
* Abnormal liver function test results at study entry (defined as alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels greater than two times the upper limit of normal range)
* Use of any investigational drug within 30 days of study entry
* Use of loop diuretics, phenytoin, warfarin, theophylline, or other methylxanthines within 30 days of study entry
* Use of more than one course of intravenous anti-pseudomonal antibiotics (at least 10 continuous days of medication use) or more than one course of inhaled anti-pseudomonal antibiotics (at least 28 continuous days of medication use) within 2 years of study entry; intravenous or inhaled anti-pseudomonal antibiotics must be stopped at least 30 days prior to study entry
* Chronic macrolide use (more than 90 day duration) in the 3 months prior to study entry
* Presence of a condition or abnormality that would compromise the participant's safety or the quality of the study data, in the opinion of the investigator
C: Inclusion criteria:

* Male or female patients ≥ 6 months old
* Diagnosis of cystic fibrosis (CF) based upon the following historical criteria performed prior to study participation:

  1. confirmed sweat chloride \> 60 mEq/L by quantitative pilocarpine iontophoresis (at least 2 tests), OR
  2. genotype with two identifiable mutations consistent with CF.
* First or early lower respiratory tract infection with Pseudomonas (P.) aeruginosa documented by either of the following:

  1. first infection defined by the first P. aeruginosa isolated from sputum or deep throat cough swab culture, OR
  2. P. aeruginosa from sputum or deep throat cough swab culture following at least 1 year of negative cultures (documented with at least 4 negative cultures during this year and no positive cultures) and no anti-pseudomonal treatment during this 1-year period, OR
  3. P. aeruginosa from sputum or deep throat cough swab culture following at least 2 years of negative cultures (documented with at least 2 negative cultures per year and no positive cultures) and no anti-pseudomonal treatment during this 2-year period.
* Written informed consent by the patient and/or parent/legal guardian according to local country regulations.

Exclusion criteria:

* History of aminoglycoside hypersensitivity or adverse reaction to inhaled aminoglycoside.
* Signs and symptoms of acute pulmonary disease, eg, pneumonia, pneumothorax.
* Administration of any investigational drug within 30 days prior to enrollment.
* Administration of loop diuretics within 7 days prior to study drug administration.
* Personal/family history of abnormal hearing, other than typical hearing loss associated with the aging process.
* Abnormal result from an audiology testing (defined as either a unilateral pure-tone audiometry test showing a threshold elevation \> 20 decibels \[dB\] at any frequency across the frequency range 0.25-8 kHz or the absence of emission at the evoked otoacoustic emission test).
* Positive urine pregnancy test at Day 1 (Baseline) for all female patients who have reached menarche.
* Use of macrolide antibiotics as a maintenance therapy for 12 or more days during the 28 days prior to Baseline.
* Antibody titers ≥ 1000 for any of the 3 P. aeruginosa exoenzymes: Exotoxin A, alkaline protease, or elastase (status to be determined between Baseline and Day 28).
D: Inclusion Criteria:

* Written informed consent obtained from patient or designated legal guardian prior to the performance of any study related procedures.
* Male or female study subjects ≥6 years of age or older
* Confirmed diagnosis of CF
* History of chronic infection with P. aeruginosa
* Study subjects must produce a screening specimen that is positive for growth of P. aeruginosa
* FEV1 ≥ 40% predicted at Screening
* SaO2 ≥ 90% at Screening while breathing room air
* Ability to comply with study medication use, study visits and study procedures as judged by the investigator
* Ability to produce sputum or be willing to undergo an induction to produce sputum for clinical evaluation
* Clinically stable with no evidence of acute upper or lower respiratory tract infection of history of pulmonary exacerbation within 4 weeks prior to screening

Key Exclusion Criteria:

* Administration of any investigational drug within 8 weeks prior to Screening
* Emergency room visit or hospitalization for CF or respiratory-related illness within 4 weeks prior to screening
* History of alcohol, medication or illicit drug abuse within the 1 year prior to screening
* History of lung transplant
* Female of childbearing potential who is lactating or is not practicing an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD)
* Positive pregnancy test
* Use of any anti-pseudomonal anitbiotics (IV antibiotics, all inhalation antibiotics, oral fluoroquinolones)within the 28 days prior to screening
* Initiation of chronic therapy (i.e. TOBI®, high-dose ibuprofen, rhDNase, macrolide antibiotics) within 28 days prior to screening
* History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of Screening
* History of mycobacterial or Aspergillus infection
* Requiring treatment within 2 years prior to screening, and/or history of allergic bronchopulmonary aspergillosis.
* History of biliary cirrhosis with portal hypertension, or splenomegaly
* History of daily, continuous oxygen supplementation or requirement for more than 2 L/min at night Change in chest x-ray at screening (or within the 3 months prior to screening)

Answer: A