FDA removes clinical hold from phase III trial of CR 845 in postoperative pain- Cara Therapeutics

The FDA has announced that it has removed the clinical hold on its adaptive Phase III trial of I.V. CR 845, from Cara Therapeutics, for postoperative pain. The clinical hold was triggered by a protocol-specified stopping criterion, based on elevated serum sodium levels, that was met during the first phase of the study. A subsequent review of unblinded safety data from the first 90 patients dosed was completed by Cara, the study’s Independent Data Monitoring Committee (IDMC), and the FDA. The results of this safety data review confirmed that increases in serum sodium levels in CR845-treated patients beyond the normal range were dose-dependent and asymptomatic with the lowest frequency of events found in the 1 microgram (ug) /kg I.V. CR845 group. Based on this safety review and an analysis of efficacy trends, the study will continue as a three-arm trial testing two doses of CR 845 (1 ug/kg and 0.5 ug/kg) versus placebo.

Comment: The CLIN3001 study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group adaptive design Phase III trial with repeated doses of I.V. CR 845 or placebo administered both prior to and following abdominal surgery in male and female patients. The trial is enrolling up to 450 patients undergoing either hysterectomy, prostatectomy, hemi-colectomy or ventral hernia repair at approximately 30 clinical sites within the U.S. Two dose levels of I.V. CR 845 (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 (AUC-24) using the patient-reported Numeric Rating Scale (NRS) score collected at pre-specified time points through 24 hours. Postoperative nausea and vomiting (PONV) will be evaluated as a secondary efficacy measure. The impact of CR 845 treatment on inflammatory biomarkers is also being explored.