This was part of the "computer ate my homework" post that I'd tried to do awhile back.
I don't think too too much of dronedarone. I may be wrong but it has issues. Starting with interactions with beta blockers, calcium-channel blockers, Digoxin, and verapamil. At least it doesn't do much to warfarin! :) But this is not good given the patient population.
It has to be taken with food.
No dose response was seen above 400mg bid, so what about lower than 400mg bid dose? No big deal maybe but older females had more AEs and higher drug levels so maybe another lower dose level should have been considered.
GI AEs were dose responsive, so what about GI bleeding which would be a bad side effect given warfarin use in this population.
Increase in serum creatinine was observed. Which at least partially/mostly lead to the problem with the Andromeda trial. That's the CHF trial that had more deaths in the drug arm than the placebo arm. SNY blamed the problem on docs stopping ACEs and ARBs "inappropriately" for the extra deaths. But I will bet you that docs did that as a response to something and most likely to serum creatinine.
Looks like dronedarone may have QT issues. Clinically relevant? maybe not. but...
Athena was started in Mid 05 and that is the trial SNY is looking at to save their bacon. It is a look at older >75 or older >70/sicker patients. While hospitalization and death is the primary, safety is the key for this trial.
I can't remember much about what else I wrote when the computer ate my homework but just some random...
CRME should pay some attention to symptoms and not just response. For instance, symptomatic vs. non-sym recurrence and degree of symptoms at recurrence should both be considered in the next phase 2. Most symptoms are chest pain, sweating, fatigue, palpitation, shortness breath, and dizziness, etc. Having 4 of 6 symptoms is not exactly a big benefit.
CRME should remember that there are better options for healthy/younger patients of AF, the need is greatest in the sicker/older population.
I don't see the FDA making CRME run a hospital/death endpoint for approval. But there is always a risk given Athena. Best to have a SPA.
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I am charging 11k Venezuelan Bolivar for my report. |
