title: A randomized, double-blind, placebo-controlled study of the efficacy and safety of MNK-795, a dual-layer, biphasic, immediate-release and extended-release combination analgesic for acute pain.
abstract: OBJECTIVE
  To investigate the efficacy and safety of a bilayer combination oxycodone (OC) and acetaminophen (APAP) analgesic with both immediate-release and extended-release (ER) components (OC/APAP ER) in patients with moderate to severe pain using an established acute pain model.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled trial. Adult patients were included in the study if they had a pain intensity score≥4 on a 0-10 numerical rating scale after bunionectomy surgery, and were randomized (1:1) to receive four doses (two tablets q12h) of OC/APAP ER or placebo.
  
  
  BACKGROUND
  NCT01484652.
  
  
  METHODS
  The primary efficacy endpoint was the summed pain intensity difference over the first 48 hours (SPID48). Secondary endpoints included SPIDs and total pain relief (TOTPAR) over the dosing intervals; time to perceptible, meaningful, and confirmed pain relief; and the proportion of patients with ≥30% reduction in pain intensity scores.
  
  
  RESULTS
  A total of 329 patients were enrolled, of whom 266 (OC/APAP ER, n=135; placebo, n=131) completed the study. The mean (SE) SPID48 was 114.9 (7.6) in the OC/APAP ER group and 66.9 (7.6) in the placebo group (P<0.0001). SPID and TOTPAR values were significantly greater with OC/APAP ER than with placebo over all time periods analyzed, and the median times to perceptible, meaningful, and confirmed pain relief were significantly shorter. More patients showed ≥30% reduction in pain intensity scores with OC/APAP ER than with placebo at all times after 0.5 hours. OC/APAP ER was generally well tolerated. A limitation of this study was the lack of an active comparator.
  
  
  CONCLUSIONS
  OC/APAP ER was efficacious and generally well tolerated in an established model of moderate to severe acute pain, providing an onset of analgesia in approximately 30 minutes and sustained pain relief over the 12 hour dosing period.
authors.affiliation: Lotus Clinical Research LLC, Huntington Hospital , Pasadena, CA , USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Singla
authors.forename: Thomas
authors.initials: T
authors.lastname: Barrett
authors.forename: Lisa
authors.initials: L
authors.lastname: Sisk
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kostenbader
authors.forename: Jim
authors.initials: J
authors.lastname: Young
authors.forename: Michael
authors.initials: M
authors.lastname: Giuliani
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D059787:Acute Pain / Q000188:drug therapy*; D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D010919:Placebos; C514822:oxycodone-acetaminophen; D000082:Acetaminophen; D010098:Oxycodone