RE:RE:There we are ... https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-non-opioid-analgesics-acute-pain-draft-guidance-industry
Fully agree with that. I would add that enhanced dissolution could possibly allow maintenance doses for chronic to be achieved with smaller but more frequent dosing. Chronic is still a risk management issue IMO.
I think that the new formulation solves the poor solubility issue, which is important in an acute pain setting. Perhaps what is more important is that the new formulation provides a second argument for a new Oten Patent (new composition). Extended IP is taking on increasing relevance as the clock ticks IMO. This by itself could justify the change in approach.
There is an interesting discussion paper at link. Well worth a read if you haven't already done so. It gives the FDA's evolving thoughts on acute pain trials, opioid sparing and expedited review. It provides some guidance for selecting primary/secondary endpoints during trials and some considerations when seeking enhanced labeling for opioid sparing. A backdrop for future Oten acute development.
TriumphSpitSix wrote: "Just wish we really understood what "significant dose reduction" meant and how it affects Acute and Chronic drug development. Acute is easy to understand but how the dose reduction affects a Chronic plan is anyone's guess."
Not a doctor or chemist but from reading the NR, I believe it is primarily related to an increase in "bioavailability" i.e., how much of the drug actually enters circulation within the body and is then available to reduce pain, inflammation, etc... Presumably, higher bioavailability would allow them to decrease the doses in both Chronic and Acute applications since more of the drug is actually utilized instead of being flushed out of the body.
Hopefully, lowering the dose would address the "elevated LTEs" which doomed the Ph.2 chronic study.
Maybe they combined it with something else or found a way to treat it to make it more soluble? Dunno, just thinking out loud...