A Randomized Phase 2 Study to Evaluate Efficacy and Safety of AR36 for Prevention of Acute Mountain Sickness

Abstract

AR36 is a pharmaceutical-grade plant extract used to support cardiovascular health in traditional Chinese medicine. Studies suggest that AR36 may prevent acute mountain sickness (AMS) during gradual ascent to high altitude. This randomized, placebo-controlled Phase 2 trial aimed to evaluate dosing regimens and assess efficacy and safety of AR36 for AMS prevention during rapid ascent. Participants received placebo, low-dose AR36 (225 mg twice daily for 14 d prior and 5 d at altitude), or high-dose AR36 (12 d placebo, 300 mg twice daily for 2 d prior and 5 d at altitude). The primary efficacy outcome was 1993 Lake Louise Scoring System (LLSS) score on the morning after ascent. Safety was assessed through the proportion of treatment-emergent adverse events (TEAEs). One hundred thirty-two participants were randomized. Mean±SD age was 31.4±8.6 (range, 19-54) y. Baseline characteristics did not differ across groups. Lake Louise Scoring System scores on Day 16 in the placebo, low-dose, and high-dose groups were 4.03 (2.88), 4.42 (3.17), and 3.5 (2.31), respectively (placebo versus low-dose, P=0.462; placebo versus high-dose, P=0.574; n=110). The incidence of AMS on Day 16 was 66.7% in the placebo, 61.1% in the low-dose, and 55.3% in the high-dose group (P=0.66). The proportion of TEAEs in the placebo, low-dose, and high-dose groups was 38.4% (81), 28.4% (60), and 33.2% (70), respectively (P=0.205; n=127). There was no statistical difference between groups in LLSS, incidence of AMS, or TEAEs. AR36 did not improve LLSS or AMS incidence using the current regimens. AR36 was well tolerated.