Sildenafil Exercise: Role of PDE5 Inhibition

Inclusion Criteria: * Confirmed diagnosis of cystic fibrosis (CF) based on the following criteria: Positive sweat chloride concentration ≥60 milliequivalents (mEq)/liter (by pilocarpine iontophoresis) and/or genotype with two identifiable disease-causing mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype * Male or female patients ≥ 9 years of age * forced expiratory volume at one second (FEV1) ≥ 30% predicted and ≤ 80% for patients ≥ 18 years of age and ≤ 85% for patients \< 18 years of age * Clinically stable without evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the 14 days prior to the screening visit * Resting oxygen saturation (room air) ≥ 85% * Patients with or without CF related diabetes * Ability to perform spirometry reproducibly (according to American Thoracic Society) criteria * Willingness to maintain chronic CF medication schedule (e.g. alternating month inhaled antibiotics) Exclusion Criteria: * Children 8 yrs. old and younger * Subjects who weigh \< 20 Kgs * History of hypersensitivity to sildenafil * Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0) * Breastfeeding, pregnant, or verbal expression of unwillingness to practice an acceptable birth control method (abstinence, hormonal or barrier methods, partner sterilization or intrauterine device) during participation in the study for women of child-bearing potential. * History of significant hepatic disease (aspartate transaminase or alanine transaminase \> 3 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension), * History of significant cardiovascular disease (history of aortic stenosis, coronary artery disease, or life-threatening arrhythmia), * History of severe neurological disease (e.g. history of stroke), * History of severe hematologic disease (e.g. history of bleeding diathesis; current international normalized ratio (INR) \> 2.0 * History of severe ophthalmologic disease (e.g. history of retinal impairment or non-arteritic ischemic optic neuritis) * History of severe renal impairment (creatinine \>1.8 mg/dL.) * Inability to swallow pills * Previous organ transplantation * Use of concomitant nitrates, α-blocker, or Ca channel blocker (currently or within one month of Visit 1) * Use of concomitant medications known to be potent inhibitors of CYP3A4 \[e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin (currently or within one month of initiation of study drug)\] (NOTE: use of azithromycin is NOT a cause for exclusion) * History of sputum or throat swab culture yielding Burkholderia cepacia or Mycobacteria massiliense within 2 years of screening * History of migraine headaches. * Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data * Initiation of a cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy less than 1 month prior to first dose of sildenafil or placebo * Use of anticoagulants * Frank pulmonary hypertension\[right ventricular systolic pressure (RVSP) \>40 mm Hg by echocardiography)