Cara Therapeutics, Inc. has resumed patient recruitment after the U.S. Food and Drug Administration removed a clinical hold on its CLIN3001 adaptive Phase 3 trial of I.V. CR845 for postoperative pain.

The CLIN3001 study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group adaptive design Phase 3 trial with repeated doses of I.V. CR845 or placebo administered both prior to and following abdominal surgery in male and female patients. The trial is enrolling up to 450 patients undergoing hysterectomy, prostatectomy, hemi-colectomy or ventral hernia repair at approximately 30 clinical sites within the U.S.

Two dose levels of I.V. CR845 (1.0 and 0.5 ug/kg, I.V.) are being compared to placebo. The primary efficacy measure is the change in pain intensity over the 24-hour postoperative period using the patient-reported numeric rating scale (NRS) score collected at pre-specified time points through 24 hours. Postoperative nausea and vomiting will be evaluated as a secondary efficacy measure. The impact of CR845 treatment on inflammatory biomarkers is also being explored.

CR845 is a peripherally acting kappa opioid receptor agonist currently in development for the treatment of acute and chronic pain and pruritus. In multiple randomized, double-blind, placebo-controlled Phase 2 trials in patients undergoing laparoscopic hysterectomy or bunionectomy procedures, I.V. CR845 treatment resulted in statistically significant reductions in both pain intensity and opioid-related side effects.

In a human abuse liability trial, I.V. CR845 demonstrated statistically significant reductions in “drug liking,” “feeling high,” “overall liking,” and “take drug again” scores in comparison to I.V. pentazocine, a Schedule IV analgesic. In more than 635 subjects dosed to date, I.V. CR845 was found to be well tolerated, without incurring the dysphoric and psychotomimetic side effects that have been reported with centrally acting (CNS-active) kappa opioid receptor agonists.

An oral formulation of CR845 has also been evaluated in a Phase 2a study in osteoarthritis patients and was shown to be well tolerated with twice a day dosing for two weeks, with evidence of decreasing pain scores during that time period.  

“We are very pleased that we were able to complete our patient safety data review with the FDA and quickly resume recruitment for the CLIN3001 trial,” Joseph Stauffer, D.O., M.B.A., chief medical officer of Cara Therapeutics, said in a statement. “Based on this safety review and an analysis of dose-related efficacy signals, this pivotal study will continue as a three-arm trial comparing two doses of CR845 (1.0 and 0.5 ug/kg) to placebo. We look forward to providing updates on our progress later this year, as we work to provide patients with a differentiated treatment option that is not limited by the side effects and abuse potential of currently available opioid pain therapeutics.”