AP30663 is a novel compound under development for pharmacological conversion of atrial fibrillation by targeting the small conductance Ca activated K (K 2) channel. The aim of this extension phase 1 study was to test AP30663 at higher single doses compared to the first-in-human trial. Sixteen healthy male volunteers were randomized into two cohorts: 6 mg/kg and 8 mg/kg intravenous single dose administration of AP30663 vs. placebo. Safety, pharmacokinetic (PK) and pharmacodynamic data were collected. AP30663 was associated with mild and transient infusion site reactions with no clustering of other adverse events but with an estimated maximum mean QTcF interval prolongation of 45.2 ms (95% CI 31.5 - 58.9) in the 6 mg/kg dose level and 50.4 ms (95% CI 36.7 - 64.0) with 8 mg/kg. PK was dose proportional with terminal half-life of around 3 hours. AP30663 in doses up to 8 mg/kg was associated with mild and transient infusion site reactions and an increase of the QTcF interval. Supplementary studies support that the QTc effect may be explained by an off-target inhibition of the I channel.