PGIC analysis indicates tapentadol ER tablets provide significant improvement in pain intensity

Sep 28 2010

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 low back pain have been published online by Expert Opinion on Pharmacotherapy. 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 30 percent improvement in pain intensity compared to placebo (39.7 percent vs. 27.1 percent, respectively; nominal p<0.001), and a significantly higher percentage of patients receiving tapentadol ER achieved at least a 50 percent improvement in pain intensity compared to placebo (27 percent vs. 18.9 percent; nominal>

To measure perceived change in overall health status, patients were asked to report their pain twice during the maintenance period and once at the end of study treatment. Results of this patient global impression of change (PGIC) analysis indicated that patients receiving tapentadol ER tablets showed a statistically significant improvement 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) to the last week of the maintenance period and over the study's entire 12-week maintenance period. Tapentadol ER significantly reduced average pain intensity compared with placebo at Week 12 of the maintenance period (tapentadol ER, -2.9 mean change [2.66 standard deviation]; placebo, -2.1 [2.33]; nominal p<0.001) and for the overall maintenance period (tapentadol ER, -2.8 [2.50]; placebo, -2.1 [2.20]; p<0.001).

The percentage of patients who completed the study in the placebo, tapentadol ER, and oxycodone CR groups was 47.6 percent, 52.2 percent and 40.5 percent, respectively. The primary reasons for treatment discontinuation in the two active treatment groups were adverse events (tapentadol ER, 16.7 percent; oxycodone CR, 32.3 percent; placebo, 4.7 percent) and lack of efficacy in the placebo group (tapentadol ER, 5.7 percent; oxycodone CR, 2.7 percent; placebo, 20.7 percent).

The rate of patient discontinuations from the study due to all treatment-emergent adverse events (TEAEs) was 16.7 percent for patients in the tapentadol ER group and 4.4 percent for the placebo group. For all gastrointestinal-related TEAEs, the discontinuation rate for patients in the tapentadol ER group was 5.3 percent versus 1.3 percent for patients in the placebo group. Specifically, 1.6 percent of tapentadol ER patients discontinued due to nausea, 1.3 percent because of constipation, and 2.5 percent due to vomiting.

The incidence of patients who reported at least one TEAE was 59.6 percent for placebo and 75.5 percent for tapentadol ER. The percentages of tapentadol ER patients experiencing common TEAEs (reported by >10 percent in any group of the study) included 20.1 percent with nausea, 13.8 percent with constipation, 19.8 percent with headache, 9.1 percent with vomiting, 11.9 percent with dizziness, 7.2 percent with pruritus, and 13.2 percent with somnolence.

"The study provides important data regarding the safety and efficacy of tapentadol ER," said Dr. Bruce Moskovitz, Therapeutic Area Leader for Pain, Ortho-McNeil-Janssen Scientific Affairs, LLC. "We are pleased that results show tapentadol ER may effectively relieve moderate to severe chronic low back pain while demonstrating a favorable tolerability profile."

In this study, patients were randomized in a 1:1:1 ratio to receive controlled, adjustable doses twice a day of tapentadol ER (100-250 mg), oxycodone HCl CR (20-50 mg) or placebo during a 15-week double-blind treatment period. There were 981 patients initially randomized in the study, though 965 patients (placebo,>

Oxycodone CR vs. Placebo

The oxycodone CR arm was compared to placebo as an active control. Results showed significant reductions in average pain intensity for the oxycodone CR group compared with the placebo group at Week 12 (oxycodone CR, -2.9 [2.52]; placebo, -2.1 [2.33]; nominal p<0.001) and over the entire maintenance period (oxycodone CR, -2.9 [2.36]; placebo, -2.1 [2.20]; nominal p<0.001). In the oxycodone CR group, the percentage of patients with at least a 30 percent and at least a 50 percent improvement did not differ significantly from placebo (30.4 percent,>

The rate of oxycodone CR patient discontinuations from the study due to all TEAEs was 31.7 percent. For gastrointestinal-related TEAEs, the discontinuation rate for patients in the oxycodone CR group was 18.3 percent. Discontinuation rates for specific gastrointestinal-related TEAEs in this group included 11.3 percent due to nausea, 4.3 percent due to constipation, and 7.0 percent due to vomiting.

The incidence of oxycodone CR patients who reported at least one treatment-emergent adverse event (TEAE) was 84.8 percent. The percentages of oxycodone CR patients experiencing common TEAEs included the 34.5 percent with nausea, 26.8 with constipation, 16.8 percent with headache, 19.2 percent with vomiting, 17.1 percent with dizziness, 16.8 percent with pruritus, and 16.2 percent with somnolence.

Study researchers also conducted additional secondary statistical analyses, which may be found in the full article, published in Expert Opinion on Pharmacotherapy and accessible online at:>

Low back pain is a common chronic pain condition and affects approximately 26 percent of adults in the United States. Current treatment includes the use of long-acting opioid analgesics for the relief of moderate to severe chronic pain. These treatments are associated with high incidences of side effects that can cause some patients to discontinue their treatment.

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. 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.