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:

* Written informed consent
* Confirmed diagnosis of CF based on the following criteria:

Positive sweat chloride greater than 60mEq/liter, and/or a genotype with 2 identifiable mutations consistent with CF, and one or more clinical features consistent with the CF phenotype

* Age \>/= 18 years of age with the potential for age 12 \>/=
* Screening Pa sputum culture
* FEV1% predicted \>/= 40 (based on Wang's equations for Males aged 12-17 and females 12-15 years, and Hankinson's equations for all other patients)

Exclusion Criteria:

* Evidence of an acute respiratory infection or pulmonary exacerbation within 4 weeks prior to day 0
* Use of systemic corticosteroids or antibiotics within 4 weeks prior to day 0, or cyclic inhaled antibiotics within 14 days prior to day 0.
* History of positive B. cepacia complex, organ transplantation, hepatic disease or venal dysfunction
* Current cigarette smoker, history of drug addiction or alcohol abuse
* Use of investigational medication or participation in an investigational study within 4 weeks prior to day 0
* Women who are pregnant or breastfeeding and patients and/or partner unwilling to use an effective form of barrier contraception throughout the study
B: Inclusion Criteria:

* Diagnosis of CF as evidenced by a sweat chloride test \> 60mEq/L or by the presence of two known CF mutations
* Male or female, ages between 10-40 years old
* \> 30 kg body weight
* FEV1 \> 35% predicted for age and height
* Clinically stable with no recent hospitalization within the past 2 weeks

Exclusion Criteria:

* Significant liver disease as defined by clinical findings of portal hypertension or cirrhosis or AST, ALT, or GGT \>2x upper limits of normal within the previous 6 months
* Poor compliance with medical regimen as assessed by CF clinic care providers
* Oral supplementation with AquADEKs or another source of beta-carotene or CoQ10 in the 2 months prior to the study
* Pregnant or lactating
* Participation in another interventional clinical trial within the previous 2 weeks
* Difficulty swallowing softgels
C: 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
D: Inclusion Criteria:

* Diagnosis of CF based on the following: sweat chloride \> 60 mEq/L and/or genotype with 2 identifiable mutations consistent with CF; (ΔF508 homozygote, or ΔF508 heterozygote with a second allele known to cause the disease, or two alleles known to cause a class I, II, or III mutation) and one or more clinical features consistent with CF.
* Male and female subjects aged ≥18 years of age
* A female subject is eligible to participate if she is of:
* Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\].
* Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until one week after the last dose.
* Patients are non-smokers or former smokers by history. Former smokers will be defined as those who have not smoked for ≥6 months. Subjects who only use chewing tobacco products may be enrolled at the discretion of the Investigator and after consultation with the GSK medical monitor.
* In the judgement of the investigator the patient is clinically stable with no change in symptoms or medication, no admissions to hospital, and no intravenous antibiotic therapy for at least 1 month prior to dosing.
* Able to perform lung function tests reliably.
* FEV1 \>40% and \<110% predicted.
* Excluding periods of exacerbation, FEV1 has not decreased by \>15% over the past 12 months
* Clinically colonized by a bacterial organism commonly seen in cystic fibrosis other than Burkholderia cepacia (i.e. Pseudomonas spp., Staphylococcus aureus, Stenotrophomonas, B. Gladioli) as evidenced by identification in sputum culture within the past year. To be eligible a CF patient must have colonization of at least one typical CF organism.
* To be eligible, female patients must have a negative pregnancy test (urine or serum) and not be nursing at screening or prior to dosing.
* Subjects must have a QTcB or QTcF \< 450 msec at screening as determined by the investigators review.
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within twice (2x) the upper limit of normal at screening and bilirubin within 1.25x ULN at screening. AST, ALT, alkaline phosphatase and bilirubin \>2.0 xULN (isolated bilirubin \>2.0xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Male subjects must agree to use one of the contraception methods listed in Section 8.1.2. This criterion must be followed from the time of the first dose of study medication until one week after the last dose.
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion Criteria:

* Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or ECG, that is not associated with cystic fibrosis.
* Neutrophil count \<1.5x109 /L
* In the judgment of the PI, the patient:
* suffers from clinically unstable pancreatic function
* has clinically significant weight loss( ≥5% after a previously stable period).
* has recent change in pancreatic enzyme requirements in the past 2 months.
* Recent viral infection (within 4 weeks of dosing), with or without steroid or antibiotic treatment. Presumed viral infection will be determined according to the judgment of the Investigator and no specific testing for virus will be required.
* Subjects unable to produce a technically acceptable sputum sample.
* Clinically significant hepatic impairment
* Evidence of cirrhosis
* Patients with elevated INR that is due to suspected vitamin K deficiency may be enrolled at the discretion of the Investigator and after consultation with the GSK medical monitor
* Blood pressure persistently \>155/95 mmHg at screening.
* Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody at screening.
* History of regular alcohol consumption averaging \>7 drinks/week for women or \>14 drinks/week for men. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits) within 6 months of screening.
* Urinary cotinine levels indicative of smoking.
* Use of oral or parenteral corticosteroids within 4 weeks of screening; regular use (\>3 x/wk) of high dose NSAIDS (e.g. \>1.6g ibuprofen/day on a regular basis), within 4 weeks of screening.
* Colonization with Burkholderia cepacia
* Subjects currently being treated for mycobacterial infection
* Subjects with presumed active Allergic Bronchopulmonary Aspergillosis (ABPA)
* Subjects who have newly started therapy with azithromycin within the past 3 months.
* In the judgment of the investigator, clinically significant hemoptysis (\> 30 cc per episode) within the last 6 months
* Donation of blood in excess of 500 mL within a 56-day period prior to dosing
* Participation in a trial with any drug within 30 days or 5 half-lives (whichever is longer), or participation in a trial with a new chemical entity within 2 months prior to first dose of current study medication, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety.
* The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, and cannabinoids. Subjects who use benzodiazepines or other anxiolytic on a regular basis can be included at the discretion of the investigator and in consultation with the GSK medical monitor
* Patients may not be on an inhaled antibiotic during the study (i.e. must be an "off-TOBI" month; cessation of TOBI or other inhaled antibiotics commences from one week prior to dosing until final PK draw). Patients on maintenance therapy with hypertonic saline solution or inhaled DNase may continue these therapies.
* Unwillingness or inability to follow the procedures outlined in the protocol.

Answer: C