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. Issue 2 (August 2015)

• Record Type: Journal Article
• Authors: Singla, Neil; Margulis, Rachel; Kostenbader, Kenneth; Zheng, Yanping; Barrett, Thomas; Giuliani, Michael J.; Chen, Yin; Young, Jim L.
• Is Part Of: Physician and sportsmedicine. Volume 43:Issue 2(2015)
• Page Start: 126
• Page End: 137
• Publication Date: 2015-08
• Subjects: Acute pain -- analgesia -- fixed-dose combination -- hydrocodone bitartrate -- opioid -- postoperative pain; Sports medicine -- Periodicals; Sports Medicine -- Periodicals; Médecine du sport -- Périodiques; Sports medicine; Sportgeneeskunde; Periodicals; 617.1027
• DOI: 10.1080/00913847.2015.1025029
• Languages: English
• ISSNs: 0091-3847

Abstract

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. Conclusion . 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.