Phase 2a study of DARA BioSciences KRN5500 in treatment of cancer pain reaches primary end-point

Researchers studying a new medication for neuropathic pain have reported intriguing findings about placebo response versus drug response from a Phase 2a proof-of-concept study. They presented their findings in a poster session at the 2011 International Conference on Accelerating the Development of Enhanced Pain Treatments.

Their findings could lead to more accurate results in future similar pain medication trials. In clinical pain trials, patients are given either the drug being evaluated or an identically appearing placebo, then report on whether the drug has helped their pain by rating it on a scale from 0 to 10. Since pain is such a subjective symptom, patient self-reporting is the only way researchers can ascertain the degree of pain management.

Subjective outcomes can be difficult to assess
In their presentation, researchers Christine K. Moore PhD, Susan E. Spruill PStat, and Linda G. Jett MSN, reported the results from a trial evaluating the safety and tolerance of a new medication, KRN5500, developed by DARA BioSciences of Raleigh, NC. In earlier studies conducted by the National Cancer Institute, the drug KRN5500 showed promise for relieving neuropathic pain which often afflicts cancer patients. It is common that patients appear to respond to the placebo in pain trials where subjective outcome data are collected. Researchers are often faced with a dilemma: Is the drug a failure or is the placebo response too great to see the drug response?

According to Dr. Moore, "One of the most significant problems in clinical trials of pain medication is that there is often not enough difference between the drug and the placebo because the placebo response is so high. Patients want to feel better. The placebo effect can be as high as 40% to 50%, requiring an even higher drug effect to show a difference."

We want to feel better so we deceive ourselves
Ms. Spruill, the study's statistician, explained, "The problem is that there is always a placebo response. That's because as humans we can manifest a psychological and/or physical response even when there is no real treatment. That effect can't be held forever, but we can certainly be tricked for a short period of time. And pain is one of those areas in which we're good at tricking ourselves." The placebo response should really be thought of as background noise, the team suggests. What researchers look for is a clinical benefit over and above what is in that background, "which is why we need to study drug effects in parallel with a placebo," adds Ms. Spruill.

It really was the drug
Although this particular trial had 19 patients, it had a low placebo response, enabling the results to be more easily interpreted. Dr. Moore said the study was designed first to evaluate the safety profile of the medication, and secondly to evaluate pain response to see any potential "signal" that could have a beneficial effect. They got more than they expected; they found in this trial that KRN5500 was actually both statistically and clinically significant in alleviating neuropathic pain, reaching its primary end-point - reduction of pain from baseline. The patients who took the drug decreased their pain scores by an average of 2 units on a numeric rating scale, while patients who took the placebo showed little to no change in their pain scores. Furthermore, all patients in this trial were already on other medications for their pain; they took the study drug in addition to their usual pain management.

The researchers are now looking more closely into the experimental design and clinical conduct of this trial as they attempt to understand why such a small study was so successful. They believe that one of the reasons there was a low placebo response is that patients were very sick and were experiencing "life changing neuropathic pain." The patients were willing to participate even knowing there was a possibility they might get the placebo, and they agreed to try to stay in the study for at least 4 and up to 8 weekly doses over a 10 week period. Patients held no false hopes that the drug would cure their cancer and understood that that it was being given only for treatment of pain and the improvement in quality of life that might result. More studies of KRN5500 are planned.