Clinical trial NCT00877799
Conditions: Acute Pain
Keywords: pain acute pain visceral pain kappa agonist opioid analgesics peripheral nervous system agents physiological effects of drugs surgery hysterectomy post-operative post-operative complications
Sponsor: Cara Therapeutics, Inc.
Start date: 2009-03-01; Completion date: 2010-01-01
Enrollment: 114 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the effectiveness and safety of single intravenous doses of the kappa opioid agonist CR845 in relieving pain in patients following laparoscopic-assisted hysterectomy surgery. The study protocol was divided into two parts with subjects either dosed with study drug the day following surgery (Cohort 1), or immediately after surgery (Cohort 2).

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: CR845 administered as a single 15-min i.v. infusion at doses of 0.008 or 0.024 mg/kg on the day after surgery (Cohort 1), or at a dose of 0.040 mg/kg immediately after surgery (Cohort 2) arm 2: Matched placebo administered as a single 15-min i.v. infusion on the day after surgery (Cohort 1), or the immediately after surgery (Cohort 2)
Interventions: intervention 1: CR845 intervention 2: CR845 intervention 3: CR845 intervention 4: Placebo intervention 5: Placebo
Intervention descriptions: intervention 1: CR845 (0.024 mg/kg) administered the day after surgery (Day 1) intervention 2: CR845 (0.008 mg/kg) administered the day after surgery (Day 1) intervention 3: CR845 (0.040 mg/kg) administered immediately after surgery (Day 0) intervention 4: Matched placebo administered the day after surgery (Day 1) intervention 5: Matched placebo administered immediately after surgery (Day 0)

Protocol documents: