• Analgesic efficacy measured by patient's self reported pain level at rest using a visual analog scale on the first day after surgery (after single dose administration) [ Time Frame: 24 hours post-surgery, 12 hour period of observation after single dose is administered ] [ Designated as safety issue: No ]
  

• Time to onset of analgesic efficacy [ Time Frame: 24 hours post-surgery, 12 hour period of observation after single dose is administered ] [ Designated as safety issue: No ]
  
• Time specific and total level of pain relief (TOTPAR) [ Time Frame: Within 12 hour period of observation after single dose is administered ] [ Designated as safety issue: No ]
  
• Duration of analgesia [ Time Frame: Within 12 hour period of observation after single dose is administered ] [ Designated as safety issue: No ]
  
• Time specific pain intensity difference from baseline and total level of pain relief [ Time Frame: Within 12 hour period of observation after single dose is administered ] [ Designated as safety issue: No ]
  
• Time and requirement for rescue medication measured as survival curve of patients requesting rescue medication [ Time Frame: Within 12 hour period of observation after single dose is administered ] [ Designated as safety issue: No ]
  
• Patient satisfaction with study medication with the patient Global evaluation scale [ Time Frame: At 12 hours post-dose or prior to rescue medication ] [ Designated as safety issue: No ]
  
• Vital signs, clinical laboratory parameters, ECG [ Time Frame: Pre and post-dose until hospital discharge and 8 to 9 days after surgical procedure ] [ Designated as safety issue: Yes ]
  
• Incidence of adverse events (AEs) [ Time Frame: Until 8 to 9 days after the surgical procedure ] [ Designated as safety issue: Yes ]
  
• Sedation as measured by Ramsay sedation scale [ Time Frame: Within 12 hour period of observation after single dose is administered ] [ Designated as safety issue: No ]
  
• Anti-inflammatory effects (measured by quantification of serum TNF alpha and serum IL-6 [ Time Frame: Within 12 hour period of observation after single dose is administered ] [ 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.