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:

* Male and female patients aged ≥12 years from the date of informed consent
* Confirmed diagnosis of CF at screening
* Confirmed EPI by historical (within past 12 months) CFA \<70% without use of PERTs or current fecal elastase \<50 µg/g stool at screening
* Currently receiving PERT with a commercially available pancreatic enzyme
* Currently on stable treatment with proton pump inhibitors or H2 receptor antagonists
* Clinically stable condition without evidence of acute respiratory disease or any other acute condition

Exclusion Criteria:

* History of fibrosing colonopathy
* History of significant bowel resection, in the opinion of the investigator, or solid organ transplant
* History of being refractory to pancreatic enzyme replacement
* Current diagnosis or history of distal intestinal obstruction syndrome
* Current diagnosis of small intestinal bacterial overgrowth, ileus or acute abdomen
* A body mass index percentile \<10%
B: Inclusion Criteria:

* Signed informed consent given by the subject, or the parents, or a legally acceptable representative. If required by the Institutional Review Board/Ethics Committee (IRB/IEC), assent will be given by the subject
* Age ≥ 12 years
* Subjects who are able to swallow capsules with each meal and snacks
* Diagnosis of Cystic Fibrosis (CF) confirmed by two positive chloride sweat tests or gene analysis
* Diagnosis of pancreatic exocrine insufficiency proven by:

  1. Coefficient of fat absorption (CFA) \< 70% without supplementation
  2. or Human fecal elastase \< 50 μg/g stool
* Currently receiving treatment with a commercially available pancreatic enzyme product and on a continuous dose of this product for more than 3 months
* Clinically stable condition without evidence of acute respiratory disease within 1 month of enrollment
* Stable body weight defined as no more than a 5% decline within 3 months of enrolment
* Females of child-bearing potential should agree to continue using a medically acceptable method of birth control throughout the study and for 30 days immediately after the last dose of study drug. Medically acceptable methods of birth control include bilateral tubal ligation or the use of either a contraceptive implant, a contraceptive injection (Depo-Provera™), an intrauterine device, or an oral contraceptive taken within the past 3 months where the subject agrees to continue using during the study or to adopt another birth control method, or a double-barrier method which consists of a combination of any two of the following: diaphragm, cervical cap, condom, or spermicide.

Exclusion Criteria:

* Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic (except underlying disease), hematologic/immunologic, head, ears, eyes, nose, throat, dermatologic/connective tissue, musculoskeletal, metabolic/nutritional (except underlying disease), endocrine (except diabetes mellitus), neurologic/psychiatric, allergy, recent major surgery, or other relevant diseases as revealed by history, physical examination and/or laboratory assessments, which could limit participation in or completion of the study
* History of acute abdomen
* History of fibrosing colonopathy
* History of distal intestinal obstruction syndrome (DIOS) within 6 months prior to enrollment
* Solid organ transplant or surgery affecting the large bowel other than appendectomy
* Small bowel surgery that significantly affected absorptive capacity (e.g. gastrectomy or pancreatectomy)
* Pregnancy or lactation
* Any type of malignancy involving the digestive tract in the last 5 years
* Celiac disease or Crohn's disease
* Known allergy to pancreatin or inactive ingredients (excipients) of pancreatin capsules
* Suspected non-compliance or non-cooperation
* Intake of experimental drugs within 30 days prior to study start
* Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subject's participation in or ability to complete the study
* Diagnosis of human immunodeficiency virus in medical history.
C: Inclusion Criteria:

1. Definitive diagnosis of CF based on the following:

   * One clinical feature consistent with CF and
   * Either a genotype with 2 identifiable mutations known to cause CF or a sweat chloride concentration \>60 mEq/L by pilocarpine iontophoresis
2. Pancreatic insufficiency documented by a monoclonal faecal elastase (FE) 100 μg/g stool at screening (test results within the previous 12 months are acceptable)
3. Currently receiving pancreatic enzyme replacement therapy
4. Adequate nutritional status based on the following: body mass index (BMI) \>19 kg/m2 in adult subjects or a BMI percentile 10th percentile for age in adolescent (12 to 17 years age group) subjects
5. Are clinically stable with no evidence of concomitant illness or acute upper or lower respiratory tract infection that requires antibiotics during the 7-day interval prior to screening and preceding entry into this clinical study

Exclusion Criteria:

1. Age \<12 years
2. Known contraindication, hypersensitivity, or intolerance to pork or other porcine PEPs
3. Current uncontrolled diabetes mellitus
4. History of solid organ transplantation
5. History of surgery affecting the bowel function and weight gain
D: 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.

Answer: D