title: Randomized, double-blind, placebo-controlled study of the efficacy and safety of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen tablets for acute postoperative pain.
abstract: BACKGROUND
  A fixed-dose combination biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) tablet is being developed for the management of acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate.
  
  
  METHODS
  This Phase III, randomized, double-blind, placebo-controlled, parallel-group study evaluated the analgesic efficacy and safety of IR/ER HB/APAP (n = 201) versus placebo (n = 202) over a period of 48 hours in patients with acute moderate to severe pain following unilateral bunionectomy. Patients received three tablets of placebo or IR/ER HB/APAP as an initial dose (hour 0) followed by two tablets every 12 hours for a total daily dose of 37.5/1625 mg HB/APAP on day 1 and 30/1300 mg HB/APAP thereafter. The primary efficacy outcome was the summed pain intensity difference (SPID) over the first 48 hours (SPID48) after the first dose.
  
  
  RESULTS
  SPID48 was significantly greater with IR/ER HB/APAP versus placebo (p < 0.001). SPID dosing interval analyses demonstrated consistent, superior pain relief with IR/ER HB/APAP for each dosing interval (all p < 0.001). Mean PID was greater with IR/ER HB/APAP versus placebo beginning 30 minutes after the first dose (p < 0.05), and IR/ER HB/APAP demonstrated faster median time to the onset of perceptible, meaningful, and confirmed pain relief (all p < 0.001). Mean total pain relief scores also indicated greater pain relief with IR/ER HB/APAP versus placebo throughout the 48-hour period (p = 0.012) for all comparisons. A greater proportion of IR/ER HB/APAP versus placebo patients was either "very satisfied" or "satisfied" with their pain relief (69.3% vs 49.4%; p < 0.001). Nausea was the most common treatment-emergent adverse event (TEAE; IR/ER HB/APAP, 25%; placebo, 7.9%). All TEAEs in IR/ER HB/APAP-treated patients were mild or moderate in severity.
  
  
  CONCLUSIONS
  IR/ER HB/APAP provided rapid, significant, and consistent analgesic efficacy over a period of 48 hours in an established model of acute pain and was tolerated with a safety profile similar to other low-dose opioids.
authors: Department of Anesthesia, Lotus Clinical Research LLC, Huntington Hospital , Pasadena, CA , USA.
authors: Neil
authors: N
authors: Singla
authors: Rachel
authors: R
authors: Margulis
authors: Kenneth
authors: K
authors: Kostenbader
authors: Yanping
authors: Y
authors: Zheng
authors: Thomas
authors: T
authors: Barrett
authors: Michael J
authors: MJ
authors: Giuliani
authors: Yin
authors: Y
authors: Chen
authors: Jim L
authors: JL
authors: Young
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use*; D059787:Acute Pain / Q000188:drug therapy*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000453:epidemiology / Q000209:etiology*; D019637:Orthopedic Procedures; D059408:Pain Management; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D013607:Tablets; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D013607:Tablets; D000082:Acetaminophen; D006853:Hydrocodone
keywords: Acute pain; analgesia; fixed-dose combination; hydrocodone bitartrate; opioid; postoperative pain