A randomized, double-blind, placebo-controlled phase 3 study of the relative efficacy and tolerability of tapentadol IR and oxycodone IR for acute pain

ABSTRACT

Objective: To evaluate the relative efficacy and tolerability of tapentadol immediate release (IR) and oxycodone IR for management of moderate to severe pain following orthopedic surgery (bunionectomy).

Methods: Randomized patients (N = 901) received oral tapentadol IR 50 or 75 mg, oxycodone HCl IR 10 mg, or placebo every 4–6 h over a 72-h period following surgery. Acetaminophen (≤2 g) was allowed in the first 12 h after the first dose of study drug. In the primary analysis, tapentadol IR (50 and 75 mg) was evaluated for efficacy superior to placebo and non-inferior to oxycodone HCl IR 10 mg (using sum of pain intensity difference [SPID] over 48 h), and tolerability superior to oxycodone IR (using incidence of treatment-emergent adverse events [TEAEs] of nausea and/or vomiting).

Results: Statistically significantly higher mean SPID₄₈ values were observed with tapentadol IR (50 and 75 mg) and oxycodone HCl IR 10 mg than placebo (all p < 0.001). The efficacy of tapentadol IR 50 mg and 75 mg was non-inferior to oxycodone HCl IR 10 mg. The incidence of TEAEs of nausea and/or vomiting was statistically significantly lower with tapentadol IR 50 mg versus oxycodone IR 10 mg (35 vs. 59%; p < 0.001). No statistically significant difference in the incidence of nausea and/or vomiting was observed between tapentadol IR 75 mg and oxycodone IR 10 mg (51 vs. 59%; p = 0.057). A possible limitation of this study was that the intense dose and patient monitoring may not represent real-world situations and may result in higher incidences of TEAEs than expected in a practice setting; this bias would be similar for all treatment groups.

Conclusions: Clinically meaningful and statistically significant improvements were observed with tapentadol IR 50 mg and 75 mg compared with placebo for the relief of moderate-to-severe acute pain after orthopedic surgery. Tapentadol IR 50 mg and 75 mg were non-inferior to oxycodone HCl IR 10 mg for the treatment of acute pain based on the primary efficacy endpoint of SPID₄₈ and the pre-specified margin of 48 points. The incidence of nausea and/or vomiting was statistically significantly lower for tapentadol IR 50 mg and numerically lower for tapentadol IR 75 mg than for oxycodone HCl IR 10 mg.

Trial Registry Information::

• NCT00613938

Key words: :

• Analgesia
• Gastrointestinal tolerability
• Mu-opioid receptor agonism
• Norepinephrine reuptake inhibition
• Postoperative pain

Transparency

Declaration of funding

Writing support and publication support for this article provided by MedErgy was funded by Johnson & Johnson Pharmaceutical Services, L.L.C., and Grünenthal GmbH. The authors were not compensated and retained full editorial control over the content of the manuscript.

Declaration of financial/other relationships

E.C. has disclosed that he is a contractor with Johnson & Johnson. D.U., C.R., A.O. and C.O. has disclosed that they are employees and stockholders of Johnson & Johnson. J.-U.S. have disclosed that he is an employee of Grünenthal GmbH. S.D is an employee of Premier Research.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 and Peer Reviewer 2 have disclosed they have no relevant financial relationships.

Acknowledgments

Editorial support for the writing of this manuscript was provided by Alyssa Tippens, PhD, of MedErgy. The authors acknowledge the contributions of Daniel Solorio, BA, senior project manager, Premier Research Group Limited, Austin, TX.

Erratum

[Early Online citation]

The Early Online version of this article published online ahead of print on 18 May 2009 contained an error in Figure 2 (p.1556) and Figure 3 (p.1557) in the labelling and key concerning the dosage of oxycodone HCL - this has been corrected to the correct dosage of 10mg in the issue version of the article shown here (and as reposted on 5 June 2009).