Tapentadol ER Effective for Moderate to Severe Chronic Diabetic Peripheral Neuropathy

HONOLULU, HITapentadol extended-release (ER) is a safe and effective option for the management of moderate to severe neuropathic pain associated with diabetic peripheral neuropathy (DPN), investigators reported at the American Pain Society's 31st Annual Scientific meeting.

Christine Rauschkolb, MD, PhD, from the Janssen Research & Development, Titusville, NJ, and colleagues conducted a Phase 3, randomized-withdrawal, placebo-controlled study to evaluate the efficacy and tolerability of tapentadol ER in adult patients with moderate to severe, painful DPN with symptoms for ≥6 months who had a ≥3-month history of analgesic use for painful DPN.

Patients were titrated to an optimal dose (balancing efficacy and tolerability) of 100–250mg of tapentadol ER twice daily during the 3-week open-label period. Following the titration period, patients with ≥1-point reduction in pain intensity at the end of titration were randomized (1:1) to receive placebo or their pre-determined optimal dose of tapentadol ER for 12 weeks (double-blind, fixed dose, maintenance phase). The primary efficacy endpoint was mean change in average pain intensity.

Using an 11-point numerical rating scale, patients recorded their average pain intensity twice daily (average pain during previous 12 hours) from the beginning of the study until Week 12 of the double-blind maintenance phase (last observation carried forward). Of the 459 patients enrolled, 358 patients completed the open-label titration period; 318 patients (placebo, n=152; tapentadol ER, n=166) were randomized and received at least one dose of study medication.

Mean (SD) pain intensity at study start versus Week 12 of the double-blind maintenance phase, respectively, was: tapentadol ER, 3.70 (1.78) vs. 4.01 (2.23); placebo, 3.53 (2.17) vs. 4.83 (2.60). Mean (SD) change in average pain intensity from the start to Week 12 of the double-blind maintenance phase was: tapentadol ER, 0.28 (2.04); placebo, 1.30 (2.43) (least-squares mean difference for tapentadol ER vs. placebo, –0.95 [95% CI: –1.42 to –0.49]; P<0.001 favoring tapentadol ER).

In the open-label safety population, 76.0% of patients (349 of 459) reported ≥1 treatment-emergent adverse event; those that occurred in ≥5% of patients in the tapentadol ER (vs. placebo) groups during the double-blind maintenance included nausea (21.1% vs. 9.9%), vomiting (12.7% vs. 4.6%), fatigue (7.2% vs. 0.7%), and dizziness (7.2% vs. 2.0%).

The investigators concluded that tapentadol ER dosed at 100–250mg twice daily was effective and well tolerated for the management of moderate to severe, neuropathic pain associated with DPN in adults.