Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial With Aztreonam Lysinate for Inhalation in Cystic Fibrosis Patients With Pulmonary P. Aeruginosa Requiring Frequent Antibiotics (AIR-CF2)
Brief 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).


Options:
A: 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.
B: Inclusion Criteria:

* Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele
* Forced expiratory volume in 1 second (FEV1) of 40% to 90% (inclusive) of predicted normal for age, gender, and height at Screening.
* No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
* Willing to use highly effective birth control methods during the study

Exclusion Criteria:

* History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
* Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 of the study
* History of alcohol, medication or illicit drug abuse within one year prior to Day 1
* Abnormal liver function ≥ 3x the upper limit of normal
* Abnormal renal function at Screening
* History of solid organ or hematological transplantation
* Pregnant, planning a pregnancy, breast-feeding, or unwilling to follow contraception requirements
* Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to Screening
* Use of inhaled hypertonic saline treatment
* Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4)
C: Inclusion Criteria:

CF cohort:

Diagnosis of CF determined by

* a sweat chloride of \>60 mEq/L and/or
* detection of 2 disease causing CFTR mutations with evidence of organ involvement.

Healthy controls:

* Age-matched

Exclusion Criteria:

CF cohort:

* Lacking ability to cooperate of patients /their families, respectively

Healthy controls:

* Other diseases causing abdominal symptoms (Inflammatory bowel disease (IBD), alpha 1 antitrypsin deficiency, celiac disease, food allergy, gastroenteritis, etc.)
D: Inclusion Criteria:

* Male or female with a confirmed diagnosis of cystic fibrosis defined by:

  * Clinical features consistent with the diagnosis of CF; AND
  * Sweat chloride ≥60 mmol/L by pilocarpine iontophoresis; OR
  * Genotypic confirmation of CFTR mutation
* Aged 18 years or older
* Ability to provide sputum samples for microbiological evaluation throughout the study either spontaneously or induced.
* Chronic colonization with Burkholderia spp. defined as at least two positive microbiological cultures in expectorated sputum within the last 12 months from Visit 1.
* Use of inhaled aztreonam three times daily in a 4 weeks on/off cycle treatment regimen or a continuous intake regimen for at least 4 weeks before screening visit. For on/off cycles, screening visit should take place in the off phase. Randomization visit should take place the first day "on" to harmonize the aztreonam inhalation period with the IMP intake period.
* Willingness to stop treatment with other inhaled antibiotics.
* At Screening no clinical or laboratory findings suggestive of significant pulmonary illness, other than CF, which in the opinion of the investigator would preclude participation in the study.
* FEV1 greater than 25% of the predicted normal value following adjustment for age, gender, and height according to the Global Lung Initiative
* Female subjects of child bearing potential and male subjects participating in the study who are sexually active must use acceptable contraception. Female subjects documented as being of non-child-bearing potential are exempt from the contraceptive requirements.
* Provision of written informed consent.

Exclusion Criteria:

* Changes in underlying therapy within the 14 days prior to Day 0. Subjects must be willing to remain on the same underlying stable therapy regimens for the duration of the study until the final follow-up visit at Day 98.
* Changes in physiotherapy technique or schedule within 14 days prior to Day 0.
* Prohibited medications within 7 days prior to Day 0. Concomitant administration of inhaled mannitol or hypertonic saline within 7 days prior to Day 0.
* Concomitant use of inhaled antibiotics other than aztreonam.
* Pulmonary exacerbation within 28 days of Screening.
* Lactose intolerance/milk allergy.
* On-going acute illness. Subjects must not have needed an outpatient visit, hospitalization or required any change in therapy for other pulmonary disease between Screening and Day 0.
* History of, or planned organ transplantation.
* Active allergic bronchopulmonary aspergillosis (ABPA) in the last 12 months prior to Screening, defined as having received treatment for ABPA.
* Inability or unwillingness to provide sputum samples for microbiological evaluation throughout the study either spontaneously or induced by means of using inhaled hypertonic saline.
* Clinically significant abnormal findings on haematology or clinical chemistry. In addition, any value ≥ 3 x the upper limit of normal will exclude the subject from participating in the study.
* Subjects unable to perform pulmonary function tests according to the ATS/ERS criteria.
* Pregnant or breast-feeding women. A negative urine pregnancy test must be demonstrated in females of child-bearing potential at Screening.
* Subjects who have participated in any interventional clinical trial within the 28 days prior to Day 0.
* Subjects with documented or suspected, clinically significant, alcohol or drug abuse, as determined by the Investigator.
* Current malignant disease (with the exception of basal cell carcinoma; BCC).
* Any serious or active medical or psychiatric illness, which in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol.
* Patients not willing/able to follow the study instructions.
* Resistance to aztreonam, or intolerance to aztreonam or any of its excipients.

Answer: A