Tapentadol immediate-release for acute postbunionectomy pain: a phase 3, randomized, double-blind, placebo-controlled, parallel-group study in Taiwan

Abstract

Objective:

To evaluate the efficacy and safety of tapentadol immediate-release (IR) for treating acute pain following orthopedic bunionectomy surgery in a Taiwanese population.

Methods:

This was a phase 3, randomized, double-blind, placebo-controlled, parallel-group bridging study in which Taiwanese patients (N = 60) with moderate-to-severe pain following bunionectomy were randomized (1:1:1) to receive tapentadol IR 50 or 75 mg or placebo orally every 4–6 hours over a 72 hour period. The primary endpoint was the sum of pain intensity difference over 48 hours (SPID₄₈), analyzed using analysis of variance.

Results:

Out of 60 patients randomized (mainly women [96.7%]; median age 44 years), 41 (68.3%) completed the treatment. Mean SPID₄₈ values were significantly higher for tapentadol IR (p ≤ 0.006: 50 mg, p ≤ 0.004: 75 mg) compared with placebo. Between-group differences in LS means of SPID₄₈ (vs. placebo) were tapentadol IR 50 mg: 105.6 (95% CI: 32.0; 179.2); tapentadol IR 75 mg: 126.6 (95% CI: 49.5; 203.7). Secondary endpoints including SPID at 12, 24, and 72 hours, time to first use of rescue medication, cumulative distribution of responder rates, total pain relief and sum of total pain relief and sum of pain intensity difference at 12, 24, 48, and 72 hours, and patient global impression of change showed numerically better results supporting that tapentadol IR (50 and 75 mg) was more efficacious than placebo in relieving acute pain. The most frequent treatment emergent adverse events reported in ≥10% patients in either group were dizziness, nausea, and vomiting. A limitation of this study may possibly include more controlled patient monitoring through 4–6 hour dosing intervals, which reflects optimal conditions and thus may not approximate real-world clinical practice. However, all treatment groups would be equally affected by such bias of frequent monitoring, if any, since it was a randomized and double-blind study.

Conclusions:

Tapentadol IR treatment significantly relieved acute postoperative pain and was well tolerated in a Taiwanese population.

ClinicalTrials.gov identifier:

NCT01813890.

Keywords: :

• Acute pain
• Analgesic
• Bunionectomy
• Immediate-release
• Phase 3
• Tapentadol

Transparency

Declaration of funding

This study was funded by Janssen Research & Development LLC. The funder was involved in the design, data analysis, and reporting of this study.

Author contributions: Y.-J.C., C.-C.C., P.-J.H., J.H., K.K., and H.L. were involved in study design, medical monitoring, and data review and analysis for the research study. Y.-J.C., C.-C.C. and P.-J.H. were the principal investigators of the clinical study. K.K. performed the statistical analysis. All authors contributed to writing drafts of the article. All authors approved the final version of the article and submission to this journal.

Declaration of financial/other relationships

Drs. Y.J. Chen, C.C. Chiang, and P.J. Huang were all investigators for this study and have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. J.H., H.L., and K.K. have disclosed that they are employees of Janssen Research & Development LLC and own stock/stock options in the company.

CMRO peer reviewer 1 has disclosed that he has no financial relationship relevant to this study but has the following relationships: consultant for Inspirion, Baxter, Purdue Pharma LLP, Grunenthal GmhB, Iroko, and Johnson and Johnson. CMRO peer reviewers 2 and 3 have no relevant financial or other relationships to disclose.

Acknowledgments

Writing support was provided by Ashwini Patil MS of SIRO Clinpharm Pvt Ltd (funded by Janssen Research & Development) and Wendy P. Battisti PhD CMPP (of Janssen Research & Development LLC) provided additional editorial assistance.