I think you all may be over-analyzing the question and the science behind the answer. I believe the answer is more simple. First, John is absolutely correct in that the early preclinical evidence was that L/E was less effective than L/C.

Second, most clinical trial protocol decisions are unfortunately not made purely about the science and perfect research design. Rather, investigators start at that point and then modify the design based on practicality and funding. When the initial trials were designed. it was very likely that the investigators, and Orion Pharma, knew if they wanted to compare L/E to L/C, they would first have to do dosing studies to find the right combination of L/E to equate it to L/C. Otherwise, they would have had to start the trials by having volunteers who were normalized on L/C and were randomized into the L/E test group, begin the trial with potential under or overdosing of L. That would have caused all kinds of side-effect problems. This wasn't practical when you consider that no one really believed there would be a significant improvement from L/E alone. So, Orion made the decision to just test E as an adjunct add-on to L/C and test the L/C/E combination for improvement over L/C alone. In reality, there really wasn't much benefit to L/C/E (some studies showed small improvement and some no improvement).

That's my thoughts and best guess on the question. I am working with Novartis (the original distributor of E) on another trial and have a meeting with them on Wed. I will ask them the question and see if anyone knows about or remembers the original trials and the decisions behind the design protocol.