I have heard of people using them upside down, not very convenient I would think. Although I quite often forget which is the front or back or top and bottom of my Malden Compact Zip!
Would one designed for both hands have say vertical card slots so it could be used either way up without the risk of the cards falling out.
The Slimline Finsbury pictured above would seem an ideal candidate in design terms. No clasp to worry about, vertical card slots and you could use it either way around. Small rings so they won't get in the way of your hands when writing.
Or have I missed something? What would you design in to an alternative form of Filofax for left handed people?