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Abstract
Objective:
Painful diabetic peripheral neuropathy (DPN) may not be adequately managed with available therapeutic options. This phase III, randomized-withdrawal, placebo-controlled trial evaluated the safety and efficacy of tapentadol extended release (ER) for relieving painful DPN.
Research design and methods:
Patients (n = 588) with at least a 3-month history of opioid and/or non-opioid analgesic use for DPN, dissatisfaction with current treatment, and an average pain intensity score of at least 5 on an 11-point numerical rating scale (NRS; 0 = ‘no pain,’ 10 = ‘pain as bad as you can imagine’) were titrated to an optimal dose of tapentadol ER (100–250 mg bid) during a 3-week open-label phase. Subsequently, patients (n = 395) with at least a 1-point reduction in pain intensity were randomized 1:1 to receive placebo or the optimal fixed dose of tapentadol ER determined during the open-label phase for a 12-week double-blind phase.
Clinical trial registration: NCT00455520.
Main outcome measures:
The primary efficacy outcome was the change in average pain intensity from randomization, determined by twice-daily NRS measurements. Safety was assessed throughout the study.
Results:
The least-squares mean difference between groups in the change in average pain intensity from the start of double-blind treatment to week 12 was −1.3 (95% confidence interval, −1.70 to −0.92; p < 0.001, tapentadol ER vs. placebo). A total of 60.5% (356/588) of patients reported at least a 30% improvement in pain intensity from the start to the end of the open-label titration phase; of the patients who were randomized to tapentadol ER, 53.6% (105/196) reported at least a 30% improvement from pre-titration to week 12 of the double-blind phase. The most common treatment-emergent adverse events that occurred during double-blind treatment with tapentadol ER included nausea, anxiety, diarrhea, and dizziness. Potential limitations of this study are related to the enriched enrollment randomized-withdrawal trial design, which may result in a more homogeneous patient population during double-blind treatment and may present a risk of unblinding because of changes in side effects from the open-label to the double-blind phase.
Transparency
Declaration of funding
This study was funded by Johnson & Johnson Pharmaceutical Research & Development, L.L.C., and Global Development, Grünenthal GmbH, Aachen, Germany.
Declaration of financial/other relationships
M.E., D.Y.S., A.O., J.H. and C.R. have disclosed that they are Johnson & Johnson employees and shareholders. R.L. has disclosed that he is an employee of Grünenthal GmbH. S.S. is not employed by Johnson & Johnson Pharmaceutical Services, L.L.C., or Grünenthal GmbH and was not compensated for this manuscript.
Acknowledgments
Editorial support for this manuscript was provided by Ashley O’Dunne, PhD, of MedErgy, and was funded by Johnson & Johnson and Grünenthal. Although writing assistance was provided, the authors retained full editorial control over the content of the manuscript.
Data included in this manuscript have been presented at the 2009 Annual Meeting of the American Academy of Neurology, 69th Scientific Sessions of the American Diabetes Association, 2009 Annual Pain Medicine Meeting and Workshops of the American Society of Regional Anesthesia and Pain Medicine, 6th Triennial Congress of the European Federation of Chapters of the International Association for the Study of Pain, 12th International Conference on the Mechanisms and Treatment of Neuropathic Pain, 20th World Diabetes Congress of the International Diabetes Federation, 2009 National Conference on Pain for Frontline Practitioners, 26th Annual Meeting of the American Academy of Pain Medicine, and 3rd International Congress on Neuropathic Pain.