title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 εPKC and provide clinical evidence that inhibition of εPKC with KAI-1678 is not effective in the treatment of acute postoperative orthopedic pain.
authors.affiliation: Waikato Clinical Research (2008) Ltd, Hamilton, New Zealand. research@wc.net.nz
authors.forename: John E
authors.initials: JE
authors.lastname: Moodie
authors.forename: Eileen J
authors.initials: EJ
authors.lastname: Bisley
authors.forename: Saling
authors.initials: S
authors.lastname: Huang
authors.forename: Karen
authors.initials: K
authors.lastname: Pickthorn
authors.forename: Gregory
authors.initials: G
authors.lastname: Bell
mesh_terms: D018771:Arthralgia; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy* / Q000209:etiology*; D010455:Peptides / Q000627:therapeutic use*; D015990:Placebo Effect; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors*
chemical_list: C584124:KAI-1678; D010455:Peptides; D051744:Protein Kinase C-epsilon