Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Open-Label, Randomized, Phase 3 Trial to Evaluate the Efficacy and Safety of Aztreonam for Inhalation Solution (AZLI) Versus Tobramycin Inhalation Solution (TIS) in an Intermittent Aerosolized Antibiotic Regimen in Subjects With Cystic Fibrosis Followed by an Open-Label, Single Arm Extension (European Union [EU] Only)
Brief Summary: The purpose of this study was to assess the comparative safety and effectiveness of aztreonam for inhalation solution versus tobramycin inhalation solution in adult and pediatric patients with cystic fibrosis (CF) and pulmonary Pseudomonas aeruginosa (PA) infection.


Options:
A: Inclusion Criteria:

* Subjects, or their legal representative(s), must have given their written informed consent to participate in the study after receiving adequate previous information and prior to any study specific procedures
* Children (12 - 17 years) or adults \>/=18 years
* Documented diagnosis Cystic Fibrosis (CF):

  * documented sweat chloride \>/=60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) or nasal potential difference
  * either homozygous for ΔF508 genetic mutation or a compound heterozygous for 2 known CF mutations
  * and clinical findings consistent with CF
* Chronic colonization with P. aeruginosa defined as a positive respiratory tract culture (sputum or throat swab) within 12 months prior to screening and at screening (Note: subjects with negative culture at screening can, at the discretion of the investigator, be rescreened at a later date)
* Ability to perform reproducible pulmonary function tests
* Ability to produce sputum (noninduced)
* Stable pulmonary status, FEV1 \>/=35% to \</=75% (intraindividual variability +/-10% of absolute value). Note: The subject is not eligible for enrollment if the variability results in (or leads to) an FEV1 \<35%.
* Room air oximetry \>/=88% saturation
* Off antibiotics (except macrolide) and Cipro (oral) for at least 30 days prior to the administration of study drug for pulmonary exacerbation
* Stable regimen of standard CF treatment including chest physiotherapies and exercise regimens should not change during the 30 days prior to the administration of study drug and during the study (including macrolide administration unchanged in the previous 30 days)
* Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period
* Women who are willing to use an adequate method of contraception for 3 months after receiving the study drug. Adequate methods of contraception include vasectomy or condom use by their partners, diaphragm with spermicidal gel, coil (intrauterine device), surgical sterilization or oral contraceptive

Exclusion Criteria:

* Findings on screening history and physical examination unrelated to CF that could potentially affect the efficacy measurements (eg, chest surgery)
* Subjects with colonization of Pseudomonas aeruginosa and a CIPRO MIC of \>/=256 µg/ml or mg/l
* Burkholderia cepacia complex colonization of their respiratory tract within the past 12 months (documented by screen laboratory)
* Known aspergillosis (unless asymptomatic). Patients with invasive disease, ABPA with IGE \> 500 mg/dL will be excluded
* Transaminase level \>3x upper limit of normal (ULN)
* Massive hemoptysis (\>/=300 cc or requiring blood transfusion) in the preceding 4 weeks
* Intravenous antibiotic treatment for pulmonary exacerbation in the past 30 days
* Subjects with a medical disorder, condition or history of such that would impair the subject's ability to participate or complete this study in the opinion of the investigator or the sponsor
* Febrile illness within 1 week before the start of the study
* Active treatment for nontuberculosis mycobacteria
* Exposure to any investigational drug within 30 days
* Any history of allergic reaction to fluoroquinolones or other quinolones
* On oral steroids \>20 mg/day for longer than 14 days in the past 3 months
* Creatinine \>/=2x ULN
B: Inclusion Criteria:

* Males or females aged 6 years and older
* Subjects with CF as diagnosed by one of the following: documented sweat chloride \>= 60 mEq/L by quantitative pilocarpine iontophoresis test, or documented sweat sodium \>= 60 mmol/L, or 2 well characterized genetic mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, or abnormal nasal potential difference with accompanying symptoms characteristic of CF
* Documented PA in an expectorated sputum or throat swab culture within 3 months prior to Visit 1 or at Visit 1
* Subjects must be able to provide written informed consent/assent prior to any study related procedures; parent/guardian must be able to give written informed consent as necessary prior to any study related procedure
* Subjects must have received previous treatment with aerosolized antibiotics without demonstration of drug intolerance
* FEV1 \<= 75% predicted at Visit 1
* Ability to perform reproducible pulmonary function tests
* Chest radiograph at Visit 1 without significant acute findings (eg, infiltrates \[lobar or diffuse interstitial\], pleural effusion, pneumothorax); or chest radiograph or magnetic resonance image (MRI) obtained within the 180 days prior to Visit 1 without acute findings and no significant intercurrent illness; chronic, stable findings (eg, chronic scarring or atelectasis) are allowed

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 swab culture yielding B. cepacia in the previous 2 years
* Current requirement for daily continuous oxygen supplementation or requirement for more than 2 L/minute at night
* Administration of any investigational drug or device within 28 days of Visit 1 or within 6 half-lives of the investigational drug (whichever is longer)
* Known local or systemic hypersensitivity to monobactam antibiotics
* Known allergies/intolerance to tobramycin
* Inability to tolerate inhalation of a short acting beta agonist
* Changes in or initiation of chronic azithromycin treatment within 28 days prior to Visit 1
* Administration of antipseudomonal antibiotics by inhalation, intravenous or oral routes within the 14 days prior to Randomization/Visit 2
* Changes in antimicrobial, bronchodilator (BD), dornase alfa, 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
* Abnormal renal or hepatic function or serum chemistry at Visit 1, defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT) \> 5 times upper limit of normal range (ULN) or creatinine \> 2 times ULN
* Positive pregnancy test at Visit 1; all women of childbearing potential will be tested
* Female of childbearing potential who is lactating or is not (in the opinion of the investigator) practicing an acceptable method of birth control; female subjects who utilize hormonal contraceptives as one of their birth control methods must have used the same method for at least 3 months before study dosing
* Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patient treatment, assessment, or compliance with the protocol
C: 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
D: Inclusion Criteria:

* Male or female ≥12 years of age at Visit 1
* Enrolled in the CFFNPR (Patients may enroll in the Registry at Visit 1 if not previously enrolled.)
* Current hospitalization for treatment of a pulmonary exacerbation
* Planned hospital admission of at least 5 days with intravenous (IV) antibiotics at Visit 1
* Able to perform spirometry at admission and willing to perform spirometry on subsequent treatment and visit days
* Willing and able to complete symptom score daily
* Willing to return for a follow up visit at end of treatment (if necessary) and 28 days after start of IV antibiotic therapy
* Written informed consent (and assent when applicable) obtained from the participant or participant's legal representative

Exclusion Criteria:

* Previous enrollment in this study
* Treatment with IV antibiotics in the 6 weeks prior to Visit 1
* Admission to the intensive care unit for current pulmonary exacerbation
* Pneumothorax on admission
* Current hospitalization for scheduled pulmonary clean out
* Current hospitalization for sinusitis as the primary diagnosis
* Massive hemoptysis defined as \> 250 cc in a 24 hour period, or 100 cc/day over 4 consecutive days occurring within one week of Visit 1
* Current pulmonary exacerbation thought to be due to allergic bronchopulmonary aspergillosis (ABPA)
* Ongoing treatment with prednisone equivalent \>10 mg/day for greater than 2 weeks initiated prior to Visit 1
* History of solid organ transplantation Currently receiving antimicrobial therapy to treat non-tuberculous mycobacterium (e.g., M. abscessus, M. avium complex)

Answer: B