Janssen Pharmaceuticals has issued results from an investigational phase III study suggesting Nucynta ER (tapentadol) extended-release tablets were significantly more effective than placebo in providing pain management among adults with chronic moderate to severe, painful diabetic peripheral neuropathy (DPN).
The study found, among patients who had at least a one-point reduction in pain intensity during three weeks of treatment with tapentadol ER, those who continued on an optimized dose of tapentadol ER (100-250mg twice daily) for an additional 12 weeks experienced significantly better pain control compared to those who switched to placebo. Treatment-emergent adverse events reported in 10% or more of tapentadol ER-treated patients during the double-blind maintenance period included nausea (21.1%) and vomiting (12.7%).
"Painful DPN is a common and burdensome complication of diabetes, and controlling pain in people with DPN can be challenging," said Aaron I. Vinik, M.D., Ph.D., FCP, MACP, lead investigator of the study. "These data suggest tapentadol ER provides a significant reduction in chronic pain in adult patients with DPN." The most common type is diabetic peripheral neuropathy, which occurs in 60-70% of diabetics and causes pain or loss of feeling in the toes, feet, legs, hands and arms.
This phase III clinical trial was a randomized-withdrawal, placebo-controlled study. It enrolled adult patients who had moderate to severe, chronic painful DPN for six months or more and a history of analgesic use for painful DPN for three months or more. This trial had three phases: an open-label phase, which included a 3-week titration period during which the individually optimized tapentadol ER dose (100-250 mg two times per day) was determined for each patient; a 12-week, double-blind maintenance phase, during which patients with a one-point or greater reduction in pain intensity from beginning to end of titration were randomized either to continue taking tapentadol ER (at their optimal dose) or to receive placebo; and a follow-up period with a clinic visit at four days and a telephone interview at 10 to 14 days after discontinuation of study drug.
The primary efficacy endpoint of the study was the mean change in average pain intensity from baseline (point of randomization) to the last week of the 12-week, double-blind maintenance phase, as determined by an 11-point pain rating scale or numerical rating scale (NRS; 0='no pain,' 10='pain as bad as you can imagine').
In the open-label titration period, 459 patients received one or more doses of tapentadol ER and were included in the open-label safety population. At the start of the 3-week, open-label phase, the majority of patients (87.1%) reported severe pain (6 or more on the 11-point NRS) with a mean pain intensity of 7.3. By the end of the open-label phase, the mean pain intensity was reduced to 3.6. Treatment-emergent adverse events (TEAEs) experienced by 10% or more of patients during the open-label phase were nausea (24.4%), dizziness (17%), constipation (11.8%) and somnolence (10.7%).
A total of 358 patients completed the open-label titration period; 318 were randomized and received one or more dose of study medication (n=152 for placebo, 166 for tapentadol ER).
Following randomization, during the double-blind treatment phase to week 12, pain increased in the placebo group with a mean change in pain intensity of 1.3, while in the tapentadol ER group, efficacy was maintained, with a mean change in pain intensity of 0.28. The least-squares mean difference between the tapentadol ER and placebo groups in the change in average pain intensity was -0.95 on the 11-point NRS favoring tapentadol ER (95% CI, -1.42 to -0.49; p<0.001, tapentadol ER vs. placebo).