A randomized, double-blind, phase III study comparing multiple doses of tapentadol IR, oxycodone IR, and placebo for postoperative (bunionectomy) pain

ABSTRACT

Objective: This study evaluated tapentadol immediate release (IR) for pain relief following orthopedic bunionectomy surgery.

Methods: This randomized, double-blind, placebo- and active-controlled, phase III study included patients with moderate-to-severe pain following bunionectomy. Randomized patients (N = 603) received tapentadol IR 50, 75, or 100 mg; oxycodone HCl IR 15 mg; or placebo orally every 4–6 hours over a 72-hour period following bunionectomy. The primary endpoint was the sum of pain intensity difference (SPID) over 48 hours. Secondary endpoints included SPID over 12, 24, and 72 hours; total pain relief, and sum of total pain relief and sum of pain intensity difference (SPRID) over 12, 24, 48, and 72 hours; use of rescue medication; patient global impression of change; and onset of action assessment. Possible limitations of this study were that the intense dose monitoring and thorough nursing care were unlikely to represent actual use situations and could introduce similar bias across all treatment groups.

Clinical trial registration: NCT00364247.

Results: Mean SPID₄₈ values were significantly higher for tapentadol IR (50, 75, and 100 mg) and oxycodone HCl IR 15 mg compared with placebo (all p ≤ 0.001). The overall incidence of adverse events was 70% for tapentadol IR 50 mg, 75% for tapentadol IR 75 mg, 85% for tapentadol IR 100 mg, 87% for oxycodone HCl IR 15 mg, and 41% for placebo. Post hoc analyses showed that tapentadol IR 100 mg and oxycodone HCl IR 15 mg provided equivalent analgesia, yet tapentadol IR 100 mg had a significantly lower incidence of nausea and/or vomiting (53% vs 70%, respectively, nominal p = 0.007).

Conclusions: Multiple doses of tapentadol IR (50, 75, and 100 mg) significantly relieve acute pain after orthopedic surgery compared with placebo. These data suggest that at doses providing comparable efficacy, tapentadol IR 100 mg has improved gastrointestinal tolerability compared with oxycodone HCl IR 15 mg.

Key words: :

• Analgesics
• Bunion
• Mu-opioid receptors
• Orthopedics
• Postoperative pain
• Surgery
• Tapentadol

Acknowledgments

Declaration of interest: This study was sponsored by Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ, USA and Research and Development, Grünenthal GmbH, Aachen, Germany. Editorial support was provided by Alyssa Tippens, PhD, MedErgy Marketing, Inc. The principal investigators who participated in this study are: Stanton M. Smith, Premier Research Group, Salt Lake City, UT; Michael Golf, Premier Research Group, Austin, TX; Mark McDonnell, Premier Research Group, San Marcos, TX; Richard Pollak, Endeavor Clinical Trials, San Antonio, TX; and Ira Gottlieb, Chesapeake Research Group, LLC, Pasadena, MD (all DPM and all USA). The authors would like to acknowledge the contributions of Daniel Solorio, BA, senior project manager, Premier Research Group Limited, Austin, TX.

Notes

* The data in this paper were previously presented at the Annual Regional Anesthesia Meeting and Workshops, Playa del Carmen, Mexico, 1 May 2008; the Annual Meeting of the American Pain Society, Tampa, FL, USA, 8–10 May 2008; and the Annual Meeting of the European Society of Anaesthesiology, Copenhagen, Denmark, 31 May to 3 June 2008