Cara Therapeutics, Inc. (CARA), a biopharmaceutical company focused on developing and commercializing new chemical entities designed to alleviate pruritus and pain by selectively targeting peripheral kappa opioid receptors, today announced positive top-line data from the adaptive Phase 2/3 trial of I.V. CR845 in patients undergoing abdominal surgeries. At the 1.0 mcg/kg dose, I.V. CR845 demonstrated statistically significant reductions in pain intensity compared to placebo at all pre-specified post-operative periods of 0-6 hours (p=0.001); 0-12 hours (p=0.004); 0-18 hours (p=0.013); and 0-24 hours (p=0.032). Additionally, I.V. CR845 treatment resulted in statistically significant reductions in the incidence of post-operative nausea and vomiting over the 24-hour period post-surgery for both 0.5 and 1.0 mcg/kg doses (p=0.006; p<0.0001, respectively).
“We are very pleased that these data demonstrate the overall benefit of I.V. CR845 in both providing pain relief across surgery types up to 24 hours post-surgery and reducing post-operative nausea and vomiting, a significant medical need in the post-operative setting,” said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. “As there continues to be a critical need for new post-surgical analgesics like I.V. CR845 that lack abuse potential and traditional mu opioid side effects, we will be assessing all options, including discussions with regulators, as to how to best move this program forward.”
“The current practice of perioperative pain management anchored around traditional opioids often results in frequent opioid-related adverse events, such as nausea and vomiting, which can be debilitating and delay patients’ post-surgical recovery,” said Sabry Ayad, M.D., Professor of Anesthesiology, Anesthesiology Institute, Cleveland Clinic and one of the study’s investigators. “The ability of I.V. CR845, under standard of care conditions in the present trial, to provide not only additional pain relief but also a considerable decrease in the incidence and degree of post-operative nausea and vomiting underscores the potential of I.V. CR845 to provide meaningful clinical benefit in the immediate post-operative recovery period.”
Phase 2/3 Trial Design and Top-Line Data
The adaptive Phase 2/3 trial was a randomized, double-blind, placebo-controlled trial designed to evaluate the analgesic efficacy and safety of two doses of I.V. CR845 (0.5 mcg/kg and 1.0 mcg/kg) versus placebo given at pre-specified intervals pre- and post-surgery in 444 patients undergoing abdominal surgery, composed of 228 patients who underwent ventral hernia surgery and 216 patients who completed a hysterectomy procedure. Patients received a 2X loading dose of I.V. CR845 pre-surgery and four additional doses given at 0, 6, 12 and 18 hours after surgery. The primary endpoint was pain relief as measured by Area Under the Curve (AUC) of the Numerical Rating Scale (NRS) pain intensity scores collected over the first 24-hour period after the baseline dose (0 hour) post-surgery for all combined surgeries. In addition to safety, the secondary endpoints included incidence of vomiting, improvement in impact scores of post-operative nausea and vomiting (PONV), reduction in use of rescue analgesic medication, as well as patient global assessment at 24 hours post baseline dose after surgery.
- I.V. CR845 achieved statistical significance for the primary endpoint of pain relief over 24 hours (AUC 0-24) post-surgery with the 1.0 mcg/kg dose versus placebo (p=0.032) and also demonstrated statistical significance across two additional pre-specified sensitivity analyses for pain relief (p=0.040 and p=0.041) for the same period post-surgery. The 0.5 mcg/kg dose did not achieve statistical significance over the 0-24 hour period (p=0.076). In addition, improvement in pain AUC was statistically significant for both the 0.5 and 1.0 mcg/kg doses over 0 to 6 hours (p=0.041, p=0.001) and 0 to 12 hours (p=0.035, p=0.004) periods and also statistically significant for the 1.0 mcg/kg dose over the 0 to 18-hour period (p=0.013) post-surgery.
- At 6 and 24 hours after baseline dose post-surgery, there were statistically significant improvements in PONV impact scores with both doses of I.V. CR845 compared to placebo: 0.5 mcg/kg (6 hrs.: p=0.0072, 24 hrs.: p<0.006) and 1.0 mcg/kg (6 hrs.: p<0.0001, 24 hrs.: p<0.0001).
- There were statistically significant differences between placebo and both doses of CR845 with respect to the total use of anti-emetic medication over the first 24 hours post-surgery (0.5 mcg/kg: p=0.0003; 1.0 mcg/kg: p< 0.0001). The percentage of patients who did not take any anti-emetic medication over 24 hours was 56% for placebo compared to 70% for CR845 0.5 mcg/kg and 81% for CR845 1.0 mcg/kg.
- There was a 73% reduction in the incidence of patient-reported vomiting in the group receiving the 1.0 mcg/kg dose versus placebo (p=0.029). Although the 0.5 mcg/kg also showed reduction in vomiting, it did not reach statistical significance.
- Both doses of I.V. CR845 exhibited numerical trends toward reduced use of rescue analgesic medication compared to placebo, but did not achieve statistical significance. There was no significant effect, compared to placebo, on patient’s global assessment of medication for either dose of I.V. CR845 over the 24-hour period.
- Common adverse effects reported in the placebo and both I.V. CR845 groups were generally low and similar in incidence, and included nausea, constipation, vomiting, flatulence, headache and dyspepsia.
The full results of this trial will be presented at a future scientific or medical conference.
Cara management will host a conference call today at 8:30 a.m. EDT to discuss the data. To participate in the conference call, please dial (855) 445-2816 (domestic) or (484) 756-4300 (international) and refer to conference ID 3863718. A live webcast of the call can be accessed under “Events and Presentations” in the News & Investors section of the Company’s website at www.CaraTherapeutics.com.
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