The responsibility for minimizing placebo effects that could skew results in Z160 trials is that of Dr. Mark Versavel.
Dr. Versavel rates as a world class central nervous system (CNS) drug trial designer based on experience and success rate. He has stewarded a number of drugs through successful trials at stages from one through four (stage four trials are for extended application of licensed drugs). This includes the blockbuster drug Lyrica. Dr. Versavel was responsible for the trials that extended Lyrica's on label use to certain neuropathic pain indications.
I won't go into any more detail on Versavel's background in part because it's already been covered on this board and also because it's very easy to look that up yourself. That's the kind of DD you ought to be doing anyway. Let's just look at what he's done.
CHALLENGES IN NEUROPATHIC PAIN TRIAL DESIGN
We heard through Mr. Jason Napodano last week about the difficulties inherent in rising above the noise of placebo effect in neuropathic pain trials. It's a real concern, and well known in the pharmaceutical industry.
But some things have been learnt in the last five years about this challenge, including ways to help surmount it. And the good news is these design factors appear to have been included in the Z160 trials. Being familiar now with Dr. Versavel's record of excellence this is no surprise.
WHAT FACTORS CAN CONTRIBUTE TO FAILURE IN PAIN TRIALS DO TO HIGH PLACEBO EFFECT?
Longer pain drug trials have higher placebo effect. Why? We don't know. It's just a statistical fact that shows up when meta-analysis is done on numerous pain studies. Pregabalin failed a fourteen week study for diabetic peripheral neuropathy (DPN) back in 2009 due to unexpectedly high placebo effect.
Z160 PAIN TRIALS ARE SHORTER TRIALS. The Z160 studies are not twelve or fourteen week studies. They are SIX WEEK STUDIES. I have little doubt this was done to reduce the chances of high placebo effect.
Sentiment: Strong Buy
WHAT WERE FACTORS THAT CONTRIBUTED TO HIGH PLACEBO EFFECT IN PHN TRIALS?
With post-herpetic neuropathy there was a correlation between having had recent outbreaks of shingles and those patients with high placebo response. The pain of a recent outbreak can diminish on its own.
In the Z160 study ANY PATIENTS WITH LESS THAN SIX WEEKS TIME POST OUTBREAK HAVE BEEN EXCLUDED FROM THE STUDY. Again, this is a smart design, and more evidence of Dr. Versavel knowing his stuff.
ARE THERE CERTAIN PAIN PARAMETERS THAT HISTORICALLY REDUCE PLACEBO RESPONSE IN CLINICAL TRIALS?
Yes, they are--
Pain that is rated as very high or rather low. Both tend to respond well to placebo. You don't want either. The Z160 studies require pain scores (PI-NRS) BETWEEN 3 AND 8.
High fluctuation in pain for lower back pain (LSR). You don't want it. Z160 trials for LSR inclusion criteria states subjects must have had STABLE LEVELS OF PAIN for the preceding two weeks.
Reports of somatic or body pain. For whatever reason these people tend to be correlated with higher placebo response. You don't want them. Z160 trials SCREEN OUT APPLICANTS WITH HIGH SELF-REPORTED SOMATIC PAIN.
The take away is this. There are known problems with placebo effect in neurological pain trials. But there are also known procedures in trial design for reducing them. Zalicus has those procedures in place. That is no doubt the doing of Dr. Mark Versavel and not surprising given his excellent track record of previous successful drug trials over several decades.
Sentiment: Strong Buy