A Single-Center, Randomized, Double-Blind, Active, and Placebo-Controlled Study of KAI-1678, a Novel PKC-Epsilon Inhibitor, in the Treatment of Acute Postoperative Orthopedic Pain

Objective KAI-1678, a novel inhibitor of the interaction of the epsilon isoform of protein kinase C (ePKC) with its intracellular receptor, has demonstrated activity in countering hyperalgesia in several models of pain. In this controlled randomized trial, KAI-1678 was tested for analgesic activity in an orthopedic acute postoperative pain setting. Design Following hip or knee replacement surgery, subjects were treated with KAI-1678, ketorolac, or saline. Subjects recorded their pain intensity on a visual analog scale and rated their quality of analgesia. The pain intensity differences between baseline and the evaluations were summed over the first 4 hours. Results The analysis revealed that, while ketorolac displayed good analgesic activity, KAI-1678 was not significantly different than placebo. Analgesia quality ratings similarly did not show a difference between KAI-1678 and placebo in this pain model. A small excess of infusion site erythema was seen with KAI-1678, but otherwise the drug was safe and well tolerated. Conclusions We investigated the safety and efficacy of a novel inhibitor of ePKC and provide clinical evidence that inhibition of ePKC with KAI-1678 is not effective in the treatment of acute postoperative orthopedic pain.