ROME — Tapentadol extended release, an investigational centrally acting analgesic, proved effective both for moderate to severe diabetic peripheral neuropathy and for similarly severe chronic nociceptive pain due to osteoarthritis or low-back injury in a series of five phase III clinical trials.
Tapentadol immediate release (Nucynta) has been approved for the treatment of moderate to severe acute pain. The investigational extended release formulation is a twice-daily drug for which a New Drug Application for marketing approval is now under review at the Food and Drug Administration.
Two of the phase III studies were 15-week, double-blind, multicenter trials totaling 2,010 patients with moderate to severe pain due to osteoarthritis of the knee. They were randomized to tapentadol extended release titrated to 100-250 mg b.i.d. or oxycodone controlled release titrated to 20-50 mg b.i.d. over the first 3 weeks or to placebo.
The tapentadol extended release group showed a significant reduction in mean pain intensity scores over the course of 15 weeks compared with placebo in both trials.
The oxycodone controlled release group was significantly better than placebo in only one trial, Dr. Christine Rauschkolb reported.
The diabetic peripheral neuropathy investigation was a double-blind, 15-week, placebo-controlled study in 389 patients.
The placebo group showed significant worsening of average pain intensity over the 15 weeks. There was no change in pain intensity over time in the tapentadol extended release group, which signifies treatment efficacy, said Dr. Rauschkolb of Johnson & Johnson Pharmaceutical Research & Development, Raritan, N.J.
The double-blind, chronic low-back pain study was also 15 weeks in duration. It included 958 patients with moderate to severe pain who were randomized to tapentadol extended release, oxycodone controlled release, or placebo. Both the tapentadol and oxycodone groups experienced significantly reduced pain intensity from baseline through the end of the study, compared with placebo.
The 1-year-long safety study was an open-label trial conducted in 1,117 patients with osteoarthritis or low-back pain.
They were randomized 4:1 to tapentadol extended release at 100-250 mg b.i.d. or oxycodone controlled release at 20-50 mg b.i.d. Mean pain intensity scores improved in the tapentadol extended release group from 7.58 at baseline to 4.37 at 1 year on an 11-point scale, and from 7.61 to 4.52 with oxycodone controlled release. Nausea, vomiting, and constipation were significantly more frequent in the oxycodone controlled release arm.
In a separate pooled analysis of three randomized, double-blind phase III studies involving 980 patients who received tapentadol extended release for moderate to severe osteoarthritis or low-back pain, 1,001 patients assigned to oxycodone controlled release, and 993 on placebo, the treatment discontinuation rate was highest by far in the oxycodone arm.
The discontinuation rates were 40.6% with placebo, 43.5% with tapentadol extended release, and 61.7% with oxycodone controlled release, reported Dr. Bernd Lange of Grunenthal GmbH, Aachen, Germany.
The bottom line on this extensive randomized trial experience is that tapentadol extended release is at least as effective as oxy- codone controlled release for the management of chronic pain at a ratio of approximately 5 mg of tapentadol extended release to 1 mg of oxycodone controlled release. But tapentadol extended release is better tolerated, Dr. Lange said.
Tapentadol has both mu-opioid receptor agonist and noradrenaline reuptake inhibitor actions.
All of the studies were funded jointly by Johnson & Johnson and Grunenthal GmbH. Dr. Rauschkolb is an employee of Johnson & Johnson, and Dr. Lange is an employee of Grunenthal.