Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover Phase 1/2a Study Testing Safety/Efficacy of Advair HFA (Salmeterol, Fluticasone) in Resting & Exercising Healthy & High Altitude Pulmonary Edema (HAPE) Predisposed Subjects
The current protocol is composed of two studies. The first study is designed to carefully evaluate the safety of high-dose salmeterol/fluticasone (Advair HFA) versus placebo (hydrofluoroalkane, HFA) administration over 7 days, as well as the efficacy of the study drug to increase exercise performance, in healthy individuals exercising under hypoxic, simulated high-altitude conditions (Phase 1/2a study). The second study will examine sensitive measures of cardiopulmonary function using invasive cardiopulmonary testing, in both HAPE-sensitive and HAPE-resistant individuals, to assess the potential efficacy of salmeterol/fluticasone to prevent pulmonary edema and to enhance exercise capacity (Phase 2a) in these individuals.
• Written informed consent signed prior to entry into the study.
• Male or female age 18-50 years of age
• BMI ≥ 20 and \< 35 kg/m2
• Agreement to comply with the study-required interventions and treatment during the full duration of the study.
• In good health as determined by screening medical history, physical examination, vital signs (blood pressure, heart rate, respiratory rate and temperature), clinical laboratory tests (CBC, protime (PT) (INR)/partial thromboplastin time (PTT), thyroid stimulating hormone (TSH), Total Bilirubin, blood chemistries, urine drug screening), and a resting 12-lead Electrocardiogram with a 10 second rhythm strip.
• Adequate peripheral venous access for IV insertion and blood sample collection (assessments will be made prior to undergoing further assessments).
• HAPE-susceptible individuals (Study 2 only) must have had a medically documented (hospital admission or emergency room visit) HAPE episode characterized by noncardiogenic pulmonary edema and hypoxemia that occurred during high altitude travel in Colorado and must reside below 3,000 feet (unacclimatized individuals; non-Colorado residents).
• HAPE-resistant individuals (Study 2 only) will have had no evidence of HAPE during high altitude travel in Colorado, and must reside below 3,000 feet (unacclimatized; often being travel partners of HAPE-susceptible subjects).
• Healthy controls (Study 1 only) will all be Colorado residents.