Is it the Medication or is it the Placebo Response That's Making You Feel Better?
Scientists Are Attempting to Understand the Phenomenon
RALEIGH, N.C., March 29, 2011 (GLOBE NEWSWIRE) -- DARA BioSciences, Inc. (Nasdaq:DARA) reported that researchers studying a new medication for neuropathic pain have reported intriguing findings about placebo response from a Phase 2a proof-of-concept study. They presented their findings 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, being developed by DARA BioSciences. In earlier studies conducted by the National Cancer Institute, 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 KRN5500
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 a study of this size 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. As a result of the promising results of the first Phase II study a second Phase II study, in 40 patients, is planned to begin the first half of 2011.
About DARA BioSciences, Inc.
DARA BioSciences, Inc. is a North Carolina based biopharmaceutical development company that acquires promising therapeutic candidates and develops them through proof of concept in humans for subsequent sale or out-licensing to larger pharmaceutical companies. Presently DARA has two drug candidates with cleared IND (Investigational New Drug) Applications from the United States FDA advancing through clinical development:
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KRN5500 for the treatment of neuropathic pain – successfully completed a Phase II study and plans to initiate a second Phase II study (Q2 2011) in conjunction with the National Cancer Institute focusing on the treatment of chemotherapy induced peripheral neuropathy (CIPN); and
- DB959 for the treatment of type 2 diabetes – successfully completed a Phase Ia study and plans to initiate a Phase Ib study Q1 2011.
In addition, the Company has a pipeline of diverse drug candidates at various stages of development, with 88 US and foreign granted patents and 60 pending applications. The first drug candidate KRN5500 has successfully completed a Phase 2 clinical trial treating neuropathic pain in patients with cancer. KRN5500 met its primary endpoint and was statistically significantly (p=0.03) better than placebo. A second Phase 2 clinical trial is planned during the first half of 2011. In addition, DARA has entered into a Clinical Trial Agreement with the National Cancer Institute to study the prevention and treatment of neuropathic pain in cancer patients. The second drug candidate DB959 is an oral, highly selective, non-thiazolidinedione (TZD), first-in-class dual PPAR (peroxisome proliferator activated receptor) delta/gamma agonist in development for type 2 diabetes. A Phase 1 clinical study has been completed and the positive results were announced earlier this year. A second Phase 1 is planned to commence in the first quarter 2011 and the Company plans to announce results in the second half of 2011. In addition, DARA owns CPT-1 inhibitors intended for topical application for patients with psoriasis, a library of DDPIV inhibitors and a diverse library of approximately 1800 PPAR agonists of various molecular modalities. PPAR receptors are found throughout the human body and recent publications report that PPAR agonists may be useful in the treatment of Alzheimer's disease, cystic fibrosis, liver disease, and a variety of autoimmune diseases. Because its diverse PPAR library has the potential to address the unmet medical needs of these diseases, the Company plans to explore several of these indications.
Safe Harbor Statement
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