AGM 2024 - QUESTIONS, page-56

Sorry if this is not clearly related to the thread but given it is discussed here, I added it here.

It was always interesting to me that despite mountains of data available on the effectiveness of 2mg twice weekly (2X2), the Stage 1 of PAR002 did not include 2X2 dose as an option. It is completely understandable and smart to test lower doses. Lower doses mean less side effects generally. But you would think neither FDA, an outside consultant nor PAR (obviously this was not the company's choice) wouldn't include the most tested and effective dose into the main trial without having a back up plan.

Having said that, the trial design, the way it is worded, clearly says:
"Participants in Stage 2 will be randomly allocated to receive: One of the 3 Stage 1 PPS doseregimens selected by the DMC (none of the three are 2X2) vs placebo twice weekly". This doesn't imply a simple way to add the 2X2 dose which was not part of the three choices. And it just strikes me as odd.

Does anyone know or is aware of examples in the past for other trials when after DMC assessment, a trial added a new dose into the equation to be tested or any reference to point out the fact that the doses chosen in the 002 study are "just to see if lower doses work" and can be reworked?

I would be surprised this would be an issue and do trust the FDA process, albeit slow and onerous, does want the science to be clear and effective. But with recent events, I am less accepting of PR reassurances and I just wondered if others are aware of examples when the dose was adjusted seamlessly in other studies or whether there is PAR002 trial info that suggests it can be done easily that I have not found?

And if not, let's assume the worst - more time for further dosing study ($$, time and extreme frustration but not the end of the world if you have a LT horizon) OR trial proceeds with 1.5mgX2 - do we know more about effectiveness and chances with this dose given recent PAR correspondence?