Sildenafil Exercise: Role of PDE5 Inhibition

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)
• •History of Priapism or known penile anatomical deformities