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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.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.NCT00455520.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.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.Compared with placebo, tapentadol ER 100-250 mg bid provided a statistically significant difference in the maintenance of a clinically important improvement in pain 1 , 2 and was well-tolerated by patients with painful DPN.

This study evaluated tapentadol immediate release (IR) for pain relief following orthopedic bunionectomy surgery.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.NCT00364247.Mean SPID(48) values were significantly higher for tapentadol IR (50, 75, and 100 mg) and oxycodone HCl IR 15 mg compared with placebo (all por= 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).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.