adherence to dosing schedules for VX

VX is dosed at every 8 hours +- 20 minutes.  Has anyone seen a study showing the impact of adherence, or not, to this schedule?  I know that AIDS protease inhibitors had the same rigorous schedule in the early days, but I am not aware of any studies showing the importance of adherence to these schedules.

[APKhaos]

So, lets imagine you decide to blow off the dosing schedule as 'not important', and then discover down the line that your treatment was not successful. How would you live with the fact that the dosing schedule may have been a factor?

Its not until the pharmakinecs data from all the Phase 2 trials is analysed that they will know how the VX-950 levels are maintained between dosing. Given that nobody yet knows how sensitive this factor is,  it makes sense to stick to the schedule, right? Missing the time windows on a few doses here and there may not be significant, but the more you do it, the further you move from safe ground.

In my world,  being a trial subject has enough elements of uncertainty. Why would you want to add more??

[andiamo]

I am not thinking of deviating from the schedule.  I am interested to see if there is a correlation between treatment failures and adherence to the schedule.

Thanks for the good advice though.

[APKhaos]

..then sorry if my response was a bit uppity.

As yet, there is no data coorelating dosing schedule compliance with treatment failures. Its not clear that there will be much decent data to use for this, aside from the dosing log that all subject must use. I know that I got so foggy during tx that there were times when I was struggling to remember if I'd taken the dose, and probably screwed up my log time a few times as well.

[friole]

In as much as it is important to knock out as much of the virus as soon as you can, I think this 8-hour dosing schedule is exciting.  How often are the PCR's done?

[APKhaos]

Friole said,"How often are the PCR's done?"

I have results for Prove 1 only, but P2 & P3 seem to follow the same general study design.

Aside from the PCR taken at each of the two screening visits, there were 15 PCRs in the first 20 weeks. That's the good news. The less good news is that the first 12 weeks of Prove 1 were blinded for all Arms, so neither the clinic nor the subjects saw any PCR results until after week 12. When the week 12 PCR results were available, they delivered a summary of all 22 PCR results on one page. You could see exactly how the VL responded over time.

Now THAT was quite a day!

[andiamo]

Prove 3 is blinded for at least 24 weeks.

I also have a problem eating 300 calories at 8, 4 and midnight. I am nauseated as well, so it is hard to eat, but I force myself.

I might have a placebo; it is difficult to tell with all the side effects from the standard TX.  I try not to think about it, since I relapsed twice with standard treatment for 48 weeks.

[web52]

how are your sx? the morning dose of vx was the toughest for me. i have a very hard time eating in the morning when not on tx. having to eat 300 calories at 6 a.m. with nausea (sx) was a real challenge every day for the whole 12 weeks. friole: i like your "exciting" outlook. it's a great way to reframe the tx from
"dreaded" to "exciting" by thinking about it as killing off those buggers with every dose..

[Happyhungry]

Andiamo:

I might have a placebo; it is difficult to tell with all the side effects from the standard TX. I try not to think about it, since I relapsed twice with standard treatment for 48 weeks.
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Response from Happy Hungry;
I was in Prove 2 and there are several people around this site from Prove 1.  There was a lot of discussion about placebo vx and you should check out the archieves.  In Prove 1 and 2 it was possible to tell the placebos easily from the taste.  Unless vertex has improved the placebos in Prove 3 you should be able to find out whether you are on the real thing.  The placebo tastes neutral, chalky, some say mildly sweet.  The real Vx-950 is completely different.  It is bitter and very nasty to the taste.  If you deliberately try to eat one slowly, breaking it up in the mouth and swilling it around, you will know for sure which you have.  The real thing is not pleasant at all.
Swallowing the VX three times a day as instructed becomes a real chore.  But you just have to make yourself do it.  I would not advise messing with the schedule. VX is eliminated from the system very fast.  When you finally end your dosing, you will find that it all leaves the system within a matter of hours.  For this reason, the dosing 3 times per day is very important to maintain the level of the drug in your system.  This is MOST important during the first 4 weeks when hopefully you will be elmininating most if not all of your virions.  You need to keep your body saturated with the VX during this period.  

[web52]

hang in there. you can do it!! happy is right, my vx was terribly bitter, but others (at least 1) who was on the real vx reported it didn't taste bitter. how are your sides compared to your two previous tx?

[Electra56]

I just started Prove 3 this week.  I think I have the placebo because the pills aren't bitter- I chewed one to find out.  How do yours taste?  BTW I was told that nausea is a side effect of the protease inhibitor- so that's a positive for you in a perverse sort of way.  And FYI, even though I think I'm on placebo- I'm sticking to the tight dosing schedule +/- 20 min.- you want to kep the pressure on.  And I do feel your pain about the 300 calories...I happen to love ice cream so I can do this at 11 pm and 7 am- but I'm just making sure that I eat something rather than 300 calories per say- which can add up!  

[andiamo]

The sides seem much worse than  my previous ecperiences with TX.  Part of that is probably that I am 4 years older now and have more liver damage than before.

The pills are very bitter, so I guess it is the real thing.

[andiamo]

If you do have a placebo, you will be given the chance to try the int/rib/vx combo for 24 weeks if you do not achieve rvr.

The ice cream sounds like a great idea:).  I am sticking to the schedule 100% so far.

Thanks everyome for the support and information.