Conflict of Interest/Disclosure Summary: Dr. Pickthorn, Dr. Huang, and Dr. Bell are employees and stockholders of KAI Pharmaceuticals, Inc.
Original Research Article
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
Article first published online: 8 APR 2013
Wiley Periodicals, Inc
Volume 14, Issue 6, pages 916–924, June 2013
How to Cite
Moodie, J. E., Bisley, E. J., Huang, S., Pickthorn, K. and Bell, G. (2013), 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. Pain Medicine, 14: 916–924. doi: 10.1111/pme.12088
Brief summary of article: Nociceptive properties of protein kinase C (PKC) has been studied for nearly two decades. We found that KAI-1678—a novel inhibitor of epsilon PKC—was not an analgesic for patients with postoperative pain following total hip or total knee replacement surgery. However, a different PKC inhibitor may prove to be a safe and effective analgesic.
- Issue published online: 20 JUN 2013
- Article first published online: 8 APR 2013
- Acute Pain;
- Epsilon Protein Kinase C Inhibitor;
- Postoperative Orthopedic Pain
KAI-1678, a novel inhibitor of the interaction of the epsilon isoform of protein kinase C (εPKC) 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.
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.
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.
We investigated the safety and efficacy of a novel inhibitor of εPKC and provide clinical evidence that inhibition of εPKC with KAI-1678 is not effective in the treatment of acute postoperative orthopedic pain.