Conditions: Acute Pain
Keywords: pain acute pain kappa agonis opioid analgesia bunionectomy peripheral nervous system agents physiological effects of drugs surgery post-operative post-operative complications
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 51
Healthy volunteers: no

Brief summary:
This is a single-center, randomized, double blind, placebo controlled, parallel group proof of concept study to evaluate the analgesic efficacy as well as the safety, tolerability and pharmacokinetic profile of CR845 in patients with pain following bunionectomy surgery.

Detailed description:
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.

Arms:
arm 1: Peripheral kappa opioid receptor agonist arm 2: Matched placebo

Interventions: intervention 1: CR845 intervention 2: Placebo
Intervention descriptions: intervention 1: CR845 dosage = 0.005 mg/kg per dose, IV bolus. The initial dose was administered upon reaching a qualifying pain intensity score and followed by a supplemental dose, if requested by patient for pain. Additional doses could be administered every 8 hours up to 48 hours. intervention 2: Matching placebo administered using same dosing algorithm as the active arm

Protocol document: