I couldn't do it with one hand unless I 'shrunk' the screen for that (same on the Note 7 and S7 Edge). What was REALLY uncomfortable for me on the V20 and that eventually did make my fingers hurt was the back-button for home and fingerprint. I know that for most this is where your finger naturally rests (or so the legend goes), but for me it couldn't have been far from it. The way I hold my phone, my finger would always be either too low or too high, and had to bend it uncomfortably to reach the button.
Other than that, it was quite OK for handling but it did feel bigger than the Note.