Phase 3 safety and efficacy data comparing tapentadol extended release (ER) tablets, an investigational pain medication, to placebo in patients with moderate to severe chronic osteoarthritis knee pain have been published by Clinical Drug Investigation. In addition, this study compared oxycodone controlled release (CR) to placebo as an active control.
Tapentadol ER vs. Placebo
The study demonstrated that a significantly higher percentage of patients receiving tapentadol ER tablets achieved at least a 50 percent improvement in average pain intensity compared to placebo (32 percent vs. 24.3 percent, respectively; nominal p = 0.027), indicating a clinically significant improvement in pain intensity.
To measure perceived change in overall health status, patients also were asked to report their pain at Weeks 5 and 9 of the maintenance period and at the end of treatment. Results of this patient global impression of change (PGIC) analysis indicated that patients receiving tapentadol ER tablets showed statistically significant improvements compared with placebo (nominal p<0.001).
Primary endpoints for the study were the changes in average daily pain intensity from baseline (11-point numerical rating scale) over the last week of maintenance and over the study's entire 12-week maintenance period. Tapentadol ER significantly reduced average pain intensity from baseline to Week 12 of the maintenance period versus placebo (least squares mean [LSM] difference [95 percent confidence interval], -0.7 [-1.04, -0.33]), and throughout the maintenance period (-0.7 [-1.00, -0.33]).
The incidence of patients who reported at least one treatment-emergent adverse event (TEAE) was 61.1 percent for placebo and 75.9 percent for tapentadol ER. The percentages of tapentadol ER patients experiencing common TEAEs (reported by ≥10 percent in any group of the study) included 18.9 percent with constipation, 21.5 percent with nausea, 5.2 percent with vomiting, 10.8 percent with somnolence, 17.7 percent with dizziness, 14.8 percent with headache, 10.8 percent with fatigue, and 7.0 percent with pruritus.
The rate of patient discontinuations from the study due to all TEAEs was 19.2 percent for patients in the tapentadol ER group and 6.5 percent for the placebo group. For all gastrointestinal-related TEAEs, the discontinuation rate for patients in the tapentadol ER group was 7.3 percent versus 1.8 percent for patients in the placebo group. Specifically, 4.1 percent of tapentadol ER patients discontinued due to nausea, 1.7 percent because of constipation, and 1.2 percent due to vomiting.
"We are pleased that the study indicates that tapentadol ER may be effective in the treatment of moderate to severe osteoarthritis knee pain, and that a low number of patients discontinued the study due to gastrointestinal side effects," said Dr. Bruce Moskovitz, Therapeutic Area Leader for Pain, Ortho-McNeil Janssen Scientific Affairs, LLC. "We look forward to our ongoing discussions with the FDA regarding the potential approval of this investigational medication."
Patients in this study were randomized in a 1:1:1 ratio to receive twice daily, controlled, adjustable, oral doses of tapentadol ER (100-250 mg), oxycodone HCl CR (20-50 mg) or placebo during a 15-week double-blind treatment period. There were 1,023 patients in the study that received at least one dose of study medication (placebo,>
Oxycodone CR vs. Placebo
The oxycodone CR arm was compared to placebo as an active control. The study found oxycodone CR significantly reduced average pain intensity from baseline throughout the maintenance period versus placebo (LSM difference [95 percent confidence interval], -0.3 [-0.67, -0.00]), but not at Week 12 (-0.3 [-0.68, 0.02]). A significantly lower percentage of patients achieved at least a 50 percent improvement in average pain intensity in the oxycodone CR group compared to placebo (17.3 percent vs. 24.3 percent, respectively; nominal p = 0.023).
The rate of oxycodone CR patient discontinuations from the study due to all TEAEs was 42.7 percent. For gastrointestinal-related TEAEs, the discontinuation rate for patients in the oxycodone CR group was 26.9 percent. Discontinuation rates for specific gastrointestinal-related TEAEs in this group included 14.3 percent due to nausea, 9.4 percent due to constipation, and 8.5 percent due to vomiting.
The incidence of oxycodone CR patients who reported at least one TEAE was 87.4 percent. The percentages of oxycodone CR patients experiencing common TEAEs included the 36.8 percent with constipation, 36.5 percent with nausea, 17.8 percent with vomiting, 19.6 percent with somnolence, 19 percent with dizziness, 14.6 percent with headache, 10.2 percent experiencing fatigue, and 12.6 with pruritus.
Study researchers also conducted additional secondary statistical analyses, which may be found in the full article, published in Clinical Drug Investigation and accessible online at: http://adisonline.com/druginvestigation/Abstract/2010/30080/Efficacy_and_Safety_of_Tapentadol_Extended_Release.1.aspx.
Worldwide, osteoarthritis pain affects as many as one in four adults who are older than 65 years of age and it is one of the most common causes of disability and pain among older adults. Opioid analgesics have demonstrated efficacy in the management of moderate to severe pain and are recommended by current guidelines for chronic pain associated with osteoarthritis.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) and Grunenthal GmbH conducted this study, which J&JPRD has included as part of its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for tapentadol ER tablets for the management of moderate to severe chronic pain in patients 18 years of age or older. The FDA currently is reviewing this application and, if approved, PriCara®, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., will market tapentadol ER in the United States.
PriCara(R), Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.