Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pilot Study of the Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis
Brief Summary: The objective of this trial is to determine the safety and effect on pulmonary function of 14 days of inhaled L-arginine versus placebo administered over a period of 14 days in a cohort of CF patients.


Options:
A: Inclusion Criteria:

* Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride concentration \> 60 mEq/L and/or two well characterized disease causing CFTR gene mutations
* 14 years of age and older at enrollment
* Clinically stable at enrollment
* Ability to comply with medication use, study visits and study procedures
* FEV1 % predicted \> 40% \< 80 % as calculated by reference equations

Exclusion Criteria:

* Respiratory culture positive for: B. cepacia complex within past year or at screening
* Use of systemic corticosteroids within 30 days of screening
* Use of intravenous antibiotics or oral quinolones within 14 days of screening
* History of biliary cirrhosis, portal hypertension, or splenomegaly
* Other major organ dysfunction
* History of lung transplantation or currently on lung transplant list
* Supplemental oxygen therapy
* Oxygen saturation \< 95 % on room air
* Positive pregnancy test at screening
* Investigational drug use within 30 days of screening
* History of alcohol, illicit drug or medication abuse within 1 year of screening
* Acute respiratory symptoms
* Inability to take any form of bronchodilator
* Wheezing at the time of study
B: Inclusion Criteria:

1. Diagnosis of CF as evidenced by one or more clinical features consistent with the CF phenotype or positive CF newborn screen AND one or more of the following criteria:

   1. A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis (QPIT)
   2. A documented genotype with two disease-causing mutations in the CFTR gene
2. Informed consent by parent or legal guardian
3. Age ≥ 36 months and ≤72 months at screening visit
4. Ability to comply with medication use, study visits and study procedures as judged by the site investigator
5. Ability to cooperate with chest CT at the enrollment visit as determined by the lung function technician

Exclusion Criteria:

1. Chest CT within 8 months prior to the Screening visit
2. Acute intercurrent respiratory infection, defined as an increase in cough, wheezing, or respiratory rate with onset within 3 weeks preceding screening or enrollment visit
3. Acute wheezing at screening or enrollment visit
4. Oxygen saturation \< 95% (\<90% in centers located above 4000 feet elevation) at screening or enrollment visit
5. Other major organ dysfunction, excluding pancreatic dysfunction
6. Physical findings that would compromise the safety of the participant or the quality of the study data as determined by site investigator
7. Investigational drug use within 30 days prior to screening or enrollment visit
8. Treatment with inhaled HS at any concentration within 30 days prior to screening or enrollment visit
9. Initiation (i.e. new prescription) of any inhaled hydrating agent such as mannitol or mucolytic agents such as dornase alpha within 30 days prior to the screening or enrollment visit
10. Chronic lung disease not related to CF
11. Inability to tolerate first dose of study treatment at the enrollment visit
C: Inclusion Criteria:

* Confirmed diagnosis of CF (sweat tests/genotype)
* The subject, or their legal guardian for children under 18 years old, must provide written informed consent.
* The subject must be in stable clinical condition at the time of and for a period of 14 days prior to their recruitment into the study.
* Age \> 6 years old
* FEV1 \> 40% predicted for height, age and gender
* Proven or anticipated compliance with therapy or study protocol
* Regular attendee at a Cystic Fibrosis Clinic (\> 2 visits per year)
* Able to reproducibly perform lung function tests (spirometry)
* Relatively stable nutritional status (\< 2 kg weight loss in last 6 months and \< 5 kg weight loss in last year)
* Known to have "normal" (for CF subject) laboratory tests - haematology, biochemistry, immunology, coagulation, etc.

Exclusion Criteria:

* Requiring home oxygen (pO2 \<55mmHg or pCO2 \>50mmHg) or assisted ventilation.
* Considered "terminally ill" or listed for transplantation (either lung or liver). Subjects that are listed for transplant after being enrolled in the trial are eligible to continue in the trial.
* Subjects colonised with Burkholderia cepacia. However, if a subject becomes colonised with B. cepacia during the trial, they should continue in the trial. Subjects should be considered to be B. cepacia positive if they have had even a single lifetime isolate. In these subjects, spirometry should be measured on a dedicated spirometer.
* Cigarette smoker.
* Exposure to investigational drugs within the past 30 days.
* Major haemoptysis (\> 60 mL in a single episode) within the last twelve months.
* Concurrent illnesses eg. cor pulmonale, clinically significant liver disease (portal hypertension, varices).
* Known allergy to quinine sulphate, Glucose 6-phosphate dehydrogenase deficiency.
* Immune thrombocytopaenic purpura.
* Pregnant or lactating females.
* At risk females unwilling to use appropriate contraception to prevent pregnancy for the duration of their enrolment in the study.
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: A