Phase 2 Efficacy Trial of Z160 in Lumbosacral Radiculopathy (NCT01655849)
Primary Outcome Measure: Change in weekly average of daily pain scores (PI-NRS)
SO WHAT DEFINES A "WIN" FOR Z160?
"Pain intensity is frequently measured on an 11-point pain intensity numerical rating scale (PI-NRS), where 0=no pain and 10=worst possible pain. On average, a reduction of approximately two points or a reduction of approximately 30% in the PI-NRS represented a clinically important difference."
1. Pain. 2001 Nov;94(2):149-58, Pfizer Global Research & Development
Sentiment: Strong Buy
I have unfortunately twice dealt with severe LSR from an L4-L5 rupture blown into my sciatic nerve. The pain was excruciating and was only manageable with oxycontin, etc., prior to surgery. If z-160 is as powerful as opiates and they have selected the right patient population it would be hard not to see a big reduction in pain score IF, AND ONLY IF, these patients are not attaching the pain relief too strongly with the "high" feeling of carefreeness that comes with opiates. When it comes to self reported pain scores I do think this is a very legitimate concern. Some folks like the high, some can't stand it, hopefully their sample of patients is the latter. The other issue is that LSR can be very off and on in intensity. The pain can be triggered and relieved by all sort of things -- sitting, twisting wrong/right, etc, that are hard to put a finger on. And this will add variance to the day to day pain scoring/reporting of the sample patients, which is not helpful when trying to generate a statistically p-value, especially when the sample size is not that big. Just saying it's a bit tricker than "did the med lower cholesterol" via blood test data. Regardless, I'm long. I may trim a bit into the PII binary event if it runs up enough prior to, but I'm going to hold most through. GLTA
I agree 100% with your assessment of the difficulties of such trials. Many on this board are underestimating the difficulties in making statistically significant personal and subjective assessments of pain. I raised the same matters on another thread.
I also raised another point in that thread that I believe many are missing Inasmuch as you might be a candidate for Z-160 and putting you in a hypothetical situation, what would you do (or what do you THINK you would have done) if you were on this trial, the oxycontin was NOT made available to you for 6 weeks and you were in the placebo group wherein NO pain relieve was being given over the entire trial period? In other words, I am predicting a larger than normal drop out rate most certainly from the placebo group and very possibly from the treatment group as well in order for patients in uncontrolled pain to get back to medications they know are capable of instilling at least some relief. Because of the subjective measurement of pain levels, the true placebo effect that some may experience and a putative high drop out rate, it is my opinion that data analysis will be far more complicated than many on this board think.
I think the risk of patients in the trial have of very low probability of being in the trial to get high off another pain medication. Why would someone subject themselves to a non opioid pain medicine if they truly wanted an alternative. The patients enrolled most probably dont like the side effects of the current drug they are taking. So I think they will purely evaluate the effects on their pain. We will see.
Sorry to hear about your back pain. I personally have MRI confirmed degenerative disks in my lower back and suffer pain that can sometime be relived by stretching out muscles pulling the discs together that causes spasms. Spasms results in foot numbness and pain that requires grabbing a desk or wall to stay up. During these periods, high dose naproxen sometimes works but I quickly build tolerance to it. Advil won't touch it. Bad episodes can go on for weeks and then, like magic, completely go away for months. I know exactly what you are talking about in terms of the sporadic and unpredictable nature of this beast.
But, keep in mind that not all back pain is the same and Captain has designed excellent selection criteria to help remove noise and variability associated with LSR pain:
The subject must have a diagnosis of pain due to LSR, with all of the following characteristics:
◦The subject perceives pain in one or both lower limbs at sites that are consistent with the area innervated by the L4, L5, or S1 nerve roots, with or without other sensory symptoms in the affected areas (typically, the pain may be perceived in the buttock, thigh, calf, leg, foot, or toes).
◦The history of the pain suggests that the cause of the LSR is due to injury of the lumbosacral nerve root(s) by degenerative disease of the vertebrae in the lumbosacral spine or associated soft tissues (including the intervertebral discs).
◦The duration of pain since onset is ≥ 12 weeks.
◦Based on clinical history, the intensity of pain has been stable during the 2-week period before screening.
In the investigator's opinion, the subject's diagnosis of LSR is supported by all of the following at screening:
Based on the StEP instrument:
◾Neurological examination of lower limbs shows impaired muscle power, sensory function, or deep tendon reflexes in the territory of the affected nerve roots. Etc.........
Sentiment: Strong Buy