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.
"These results are exciting for a number of reasons," said Raymond S. Sinatra, M.D., Ph.D., Professor of Anesthesiology and Co-Director, Acute Pain, at the Yale School of Medicine, "CR845 works selectively at the site of injury and not in the brain and so provides clinically effective pain relief without side effects such as nausea, vomiting, sedation and respiratory depression that are commonly observed with morphine and other narcotic analgesics. In addition, co-administration of CR845 significantly reduced the need for PCA morphine, to an extent comparable to that observed with injectable non-steroidal anti-inflammatory drugs or acetaminophen but without risk of bleeding, or hepato-renal toxicity."
"These data further extend our understanding of the exciting potential of CR845," said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. "CR845 remains our lead product, and we look forward to concluding a development and marketing partnership as we continue to move the drug forward."
SOURCE Cara Therapeutics, Inc.