Study to Evaluate Analgesic Effect of Intravenous Administration of Kappa Agonist CR845 After Hysterectomy Surgery

• Responders on Pain Intensity(PI) and Pain Relief (PR) Composite Endpoint [ Time Frame: 15 and 30 minutes after study drug administration ] [ Designated as safety issue: No ]
  The primary efficacy endpoint was the percentage of treatment responders compared to placebo. A responder was defined as a subject who had at least a 40% reduction in their pain intensity score and a pain relief score of "some," "a lot," or "complete" at 15 and 30 min following the start of the study drug infusion.
  
  

• Total PCA Morphine Consumption in the 0-16 Hour Period Following Postoperative Study Drug Treatment [ Time Frame: 0 to 16 hours ] [ Designated as safety issue: No ]
  

• Total PCA Morphine Consumption in the 4-8 Hour Period Following Postoperative Study Drug Treatment [ Time Frame: 4 to 8 hours ] [ Designated as safety issue: No ]
  
• Total PCA Morphine Consumption in the 8-16 Hour Period Following Postoperative Study Drug Treatment [ Time Frame: 8 to 16 hours ] [ Designated as safety issue: No ]
  

Currently, the most widely used drugs to treat pain after surgery are opiates, such as morphine. Morphine works mainly by activating one of several types of opiate receptors that control some of our pain sensation - the so-called mu opiate receptors. These receptors are located in many areas of the brain and also outside of the brain. By activating these receptors, morphine provides significant pain relief, but also causes side effects that limit its use. Some of these side effects include: respiratory depression or arrest (slowed or stopped breathing), sedation (a state of calmness or extreme relaxation), euphoria (an exaggerated feeling of physical and mental well-being), constipation, nausea, vomiting, and drug addiction.

In order to avoid the side effects of morphine and other mu opiates, the present experimental drug CR845 was designed to work at a different type of opiate receptor - called kappa - that can also provide pain relief, by acting on sensory nerves outside the brain. CR845 was designed to penetrate the brain much less than other opiate drugs, which should result in pain relief similar to that of morphine, but with fewer side effects. Because CR845 activates kappa receptors instead of mu receptors, the side effects are different than with a morphine-type drug. In particular, kappa opiates, such as CR845, do not cause respiratory depression or arrest, euphoria, constipation, drug tolerance, physical drug dependence or drug addiction. For these reasons, CR845 may present a distinct advantage over other opiates that are currently used for pain relief and post-operative pain in particular.