Cara Therapeutics, Inc. today announced positive data in a Phase II proof-of-concept clinical trial of its peripherally-restricted kappa opioid agonist, CR845. The 46 patient Phase II, multi-center, double-blind, placebo-controlled study was conducted at eight hospitals in the United States and evaluated the efficacy and safety of CR845 in women following laparoscopic-assisted hysterectomy. Subjects were administered a single intravenous infusion of 0.040 mg/kg CR845 or placebo following surgery, upon reporting a moderate-to-severe pain intensity level of 5 to 8 on a 0-10 pain scale. Analgesia was first assessed by pain intensity measurements for up to 8 hours post-infusion or until the patient requested morphine by initiation of patient-controlled analgesia (PCA morphine). Subsequently, analgesia was assessed by the amount of morphine required to alleviate pain until 16 hrs after drug administration.
Significant pain relief was observed in CR845-treated patients over placebo from 4-8 hrs post-drug administration, as exemplified by a significant change in pain intensity difference (PID) scores (p<0.05). In addition, CR845-treated subjects required 32% less morphine than placebo-treated patients over the 16 hr post-drug administration (p<0.05). This morphine-sparing effect was accompanied by a substantial decrease in the incidence of undesirable side effects typically associated with morphine use, including an absence of vomiting and a 72% reduction in nausea (p<0.05) There was no evidence of centrally- mediated adverse effects or sedation after CR845 treatment.
Overall, these findings indicate that CR845 is safe and well-tolerated in these patients, with the potential to become a novel approach for the treatment of acute post-operative pain and nausea, thereby facilitating patient recovery and hospital discharge.