Safety and Efficacy of Sildenafil in Cystic Fibrosis (CF) Lung Disease

• Status: Completed
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine whether sildenafil can decrease inflammation in CF lung disease.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Jewish Health
• Collaborators: Cystic Fibrosis Foundation; Cystic Fibrosis Foundation Therapeutics
• Treatments: Phosphodiesterase Inhibitors; Sildenafil Citrate

Criteria

Inclusion Criteria:

• Confirmed diagnosis of CF based on the following criteria:

• Positive sweat chloride ≥60mEq/liter (by pilocarpine iontophoresis) and/or

• Genotype with two identifiable mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype

• Male or female patients ≥ 12 years of age

• FEV1 ≥ 50% predicted (Knudson) 31

• 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

• Ability to reproducibly perform spirometry (according to ATS criteria)

• Ability to produce at least 1mL of sputum spontaneously, or be willing to undergo sputum induction

• Ability to understand and sign a written informed consent or assent and comply with the requirements of the study

• Chronic bacterial colonization (3 documented positive cultures in the prior 2 years of which at least one was obtained in the 3 months prior to randomization)

Exclusion Criteria:

• 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

• Daily use of systemic corticosteroids and/or NSAIDs within 4 weeks of the study or as needed use within 72 hours prior to the screening visit

• History of significant hepatic (SGOT or SGPT > 3 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension), cardiovascular (history of aortic stenosis, coronary artery disease, pulmonary hypertension with right ventricular systolic pressure >55 mmHg or life-threatening arrhythmia), neurological (history of stroke), hematologic (history of bleeding diathesis), ophthalmologic (history of retinal impairment or non-arteritic ischemic optic neuritis) or renal impairment (creatinine >1.8 mg/dL.)

• Inability to swallow pills

• Previous lung transplantation

• Use of concomitant nitrates, α-blocker, or Ca channel blocker

• Use of concomitant medications known to be potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin)

• 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

• Weight less than 40 kg

• History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of screening

• Resting room air oxygen saturation <93%

• History of migraines