Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Aztreonam for Inhalation Solution (AZLI) in a Continuous Alternating Therapy (CAT) Regimen of Inhaled Antibiotics for the Treatment of Chronic Pulmonary Pseudomonas Aeruginosa Infection in Subjects With Cystic Fibrosis
Brief Summary: The primary objective of this study is to evaluate the safety and efficacy of a CAT regimen with aztreonam for inhalation solution (AZLI) and tobramycin inhalation solution (TIS) in adult and pediatric subjects with cystic fibrosis (CF) and pulmonary Pseudomonas aeruginosa (PA) infection. Participants will be enrolled in a 28 day TIS run-in phase, and will be eligible for randomization in the comparative phase if they have not received non-study oral antibiotics for a respiratory event, or IV or inhaled antibiotics for any indication between Visits 2 and 3, have not developed a condition requiring hospitalization or other change in clinical status which, in the opinion of the investigator would preclude their ability to continue in the study, and have demonstrated at least 50% TIS compliance. Participants enrolled in the comparative phase will be randomized to receive 3 cycles of treatment, each cycle consisting alternating regimens: AZLI or placebo for 28 days followed by TIS for 28 days.


Options:
A: Inclusion Criteria:

* Male or female ages less than or equal to 12 years.
* Diagnosis of CF based upon the criteria established by the 1997 CF Consensus Conference: (i) sweat chloride \> 60 mEq/L by quantitative pilocarpine iontophoresis; or (ii) genotype with two identifiable mutations consistent with CF; or (iii) an abnormal nasal transepithelial potential difference, and (iv) one or more clinical features consistent with CF.
* No prior isolation of Pa from respiratory cultures (1 or more cultures in 24 months prior to enrollment), or, if prior isolation of Pa from respiratory cultures, at least a two-year history of Pa negative cultures (1 or more cultures/year), or concurrently enrolled in the EPIC Clinical Trial.
* Signed informed consent to participate in data submission to the CFF National Patient Registry.
* Signed informed consent by parent or legal guardian.
B: Inclusion Criteria:

* 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 greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT);
  * Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
  * Abnormal nasal potential difference.
* PA present in expectorated sputum or throat swab culture at Screening.
* FEV1 between (and including) 25% and 75% predicted at Screening.
* Negative pregnancy test at Screening.
* Ability to perform reproducible pulmonary function tests.
* Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.
* Ability to provide written informed consent.

Exclusion Criteria:

* Administration of antipseudomonal antibiotics by inhalation, IV, or oral routes (including azithromycin) within 14 days of Screening.
* Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone/day or 20 mg prednisone every other day.
* History of sputum or throat swab culture yielding Burkholderia cepacia in the previous 2 years.
* History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
* Administration of any investigational drug or use of any investigational device within 28 days of Screening and within 6 half-lives of the investigational drug (whichever was longer).
* Known local or systemic hypersensitivity to monobactam antibiotics.
* Inability to tolerate short-acting bronchodilator use at least three times daily.
* Changes in protocol-permitted antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days prior to Screening or between Screening and the next visit.
* Changes in physiotherapy technique or schedule within 7 days prior to 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 at Screening.
* 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.
* Use of aerosolized hypertonic saline (except for sputum induction) during the 14 days preceding Visit 1.
C: Key Inclusion Criteria:

* Male or female study subjects must be adults (≥ 6 years of age)
* Confirmed diagnosis of CF
* History of chronic infection with P.aeruginosa
* FEV1 ≥40% of predicted at Screening
* Ability to comply with study medication use, study visits and procedures
* Ability to produce 0.5 grams of sputum

Key Exclusion Criteria:

* Administration of any investigational drug within 8 weeks to Study Day 1
* 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 1 yr. to screening
* History of lung transplantation
* Female of childbearing potential who are not practicing an acceptable method of birth control or who are lactating
* Positive Pregnancy test
* Use of any anti-pseudomonal antibiotics within 28 days prior to Study Day 1
* Initiation of chronic therapy within 28 days prior to Study Day 1
* History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years prior to screening
* History of mycobacterial and/or Aspergillus infection requiring treatment within 2 years prior to screening
* History of biliary cirrhosis with portal hypertension, or splenomegaly
D: Inclusion Criteria:

* Confirmed diagnosis of CF
* Presence of PA in 2 lower respiratory tract cultures in the 12 months prior to screening
* Forced expiratory volume (FEV)1 ≥ 25 and ≤ 75% predicted
* History of 1 hospitalization or 1 course of IV antibiotics for an acute respiratory exacerbation in the 12 months prior to screening

Exclusion Criteria:

* Concurrent use of oral, IV or inhaled antibiotics at enrollment
* Concurrent hospitalization at enrollment
* History of local or systemic hypersensitivity to monobactams or aminoglycoside antibiotics or history of aminoglycoside antibiotic associated toxicity

Answer: D