Advair HFA in Healthy and HAPE Predisposed Subjects

Both Study 1 and Study 2 are double-blinded, randomized, placebo-controlled, two-period, crossover studies. Study 1 (Phase 1/2a) is a Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover study examining safety and efficacy in healthy subjects dosed with salmeterol/fluticasone 126mcg/270mcg twice daily vs. placebo, for 7 days. Subjects will exercise under hypoxic conditions one time during each study period with the primary efficacy outcome being maximal oxygen uptake (VO2max), and secondary outcomes of arterial partial pressure of oxygen (PaO2), alveolar-arterial oxygen (Aa) gradient, and blood lactate levels. Continuous cardiac monitoring will occur during study drug dosing and for 5 days after drug discontinuation. ECGs and safety lab tests will be assessed at key intervals during drug dosing. A pause in enrollment will occur for a planned data and safety monitoring board (DSMB) safety analysis after four subjects have completed Study 1. There will also be a full review of safety data once Study 1 is complete prior to initiating Study 2. Study 2 (Phase 2a) is a Double-Blinded, Placebo-Controlled, Randomized, 2 Period, Crossover study examining efficacy and safety in both healthy (HAPE-resistant) and HAPE-susceptible subjects dosed with salmeterol/fluticasone 126mcg/270mcg twice daily. Subjects will take study drug for two days prior to hypoxic exercise testing in each period of this study, then discontinue study drug when the exercise is completed. Efficacy assessments will include VO2 max (primary outcome), right heart catheter measurements, PaO2, A-a gradients, and blood lactate. For both studies, investigators and subjects will be blinded to assignment group (order of study drug vs. placebo).