BACKGROUNDThis study evaluated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of single ascending doses (SAD) and multiple ascending doses (MAD) of S086 in healthy Chinese volunteers.RESEARCH DESIGN AND METHODSThis randomized, double-blind, placebo-controlled, Phase I clinical trial enrolled 113 subjects, including 65 subjects in the SAD (60-1080 mg) study and 48 subjects in the MAD study (180-720 mg). The safety, PK (sacubitril, LBQ657, and EXP3174) and PD (MAD study: blood pressure, pulse) of S086 were assessed.RESULTSThere were no deaths, serious adverse events, or discontinuations due to TEAEs, and there were no significant safety concerns associated with S086. PK parameters for sacubitril, LBQ657, and EXP3174 increased in a dose-dependent manner after single oral doses of S086. Plasma concentrations of sacubitril, LBQ657, and EXP3174 were maintained at steady state within 5 days of once-daily oral administration of S086. In the MAD study, S086 administration was associated with a dose-dependent decrease in mean diastolic and systolic blood pressure compared to baseline.CONCLUSIONSThe safety and PK profile profiles of S086 support the use of S086 240 mg once daily in a future Phase II study in patients with heart failure.TRIAL REGISTRATIONThe trial is registered at chinadrugtrials.org.cn (CT.gov identifier: CTR20182350 and CTR20182351).