Phase 3 study: Tapentadol ER lowers incidence of gastrointestinal adverse events

Jul 20 2010

A Phase 3 open-label study, recently published online by Pain Practice, has compared tapentadol extended release (ER) tablets, an investigational pain medication, to an existing prescription pain medication, oxycodone controlled release (CR) tablets.

The study found tapentadol ER was associated with a lower overall incidence of gastrointestinal adverse events than oxycodone CR (tapentadol ER, 52.0 percent; oxycodone CR, 64.1 percent) in patients with chronic knee or hip osteoarthritis pain or chronic low back pain, including:

• Constipation (tapentadol ER, 22.6 percent; oxycodone CR, 38.6 percent);
• Nausea (tapentadol ER, 18.1 percent; oxycodone CR, 33.2 percent); and
• Vomiting (tapentadol ER, 7.0 percent; oxycodone CR, 13.5 percent).

The median duration of treatment was substantially longer with tapentadol ER (268 days) than with oxycodone CR (59 days), and the incidence of overall gastrointestinal treatment-emergent adverse events (TEAEs) leading to study discontinuation was approximately 2.5 times greater in the oxycodone CR group than in the tapentadol ER group (oxycodone CR, 21.5 percent; tapentadol ER, 8.6 percent). In addition, the incidence of constipation leading to study discontinuation was 4.5 times greater in the oxycodone CR group than in the tapentadol ER group (oxycodone CR, 7.2 percent; tapentadol ER, 1.6 percent).

The study also found tapentadol ER provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis pain or chronic low back pain for up to one year. At baseline, mean pain intensity scores in the tapentadol ER and oxycodone CR groups, respectively, were 7.6 and 7.6; at endpoint, they had decreased to 4.4 and 4.5.

"We are encouraged by these study results as they illustrate the tolerability of tapentadol ER compared with oxycodone CR, a standard chronic pain treatment," said Dr. Bruce Moskovitz, Therapeutic Area Leader for Pain, Ortho-McNeil Janssen Scientific Affairs, LLC. "We are pleased about the possibility of bringing this important investigational compound forward to patients in the future."

This study of tapentadol ER examined its long-term safety and tolerability compared to oxycodone CR and the primary objective of this study was to evaluate the safety of twice-daily doses of tapentadol ER (100 to 250 mg) over one year. Patients were randomized in a 4:1 ratio to receive controlled, adjustable, oral, twice-daily doses of tapentadol ER (100-250 mg) or oxycodone HCl CR (20-50 mg) in open-label treatment for up to one year. There were 1,117 patients in the study that received at least one dose of study medication (tapentadol ER,>

The overall incidence of patients experiencing at least one TEAE in the study was 85.7 percent in the tapentadol ER group and 90.6 percent in the oxycodone CR group. The most common TEAEs (reported in the study by greater than 10 percent in either treatment group) included constipation, nausea, dizziness, somnolence, vomiting, headache, fatigue and pruritus. In addition to the gastrointestinal TEAEs reported above, tapentadol ER was associated with lower incidences of dizziness (tapentadol ER, 14.8 percent; oxycodone CR, 19.3 percent), fatigue (tapentadol ER, 9.7 percent; oxycodone CR, 10.3 percent), and pruritus (tapentadol ER, 5.4 percent; oxycodone CR, 10.3 percent). Oxycodone CR was associated with lower incidences of somnolence (tapentadol ER, 14.9 percent; oxycodone CR, 11.2 percent) and headache (tapentadol ER, 13.3; oxycodone CR, 7.6). In the tapentadol ER and oxycodone CR groups, respectively, TEAEs led to discontinuation in 22.1 percent and 36.8 percent of patients.

Chronic pain, affecting an estimated 100 million Americans, continues to be a significant medical challenge in the United States. Osteoarthritis pain and low back pain are particularly prevalent – osteoarthritis pain affects 27 million Americans, and chronic low back pain is the most common cause of disability in developed countries.

Although currently available long-acting opioid analgesics have been shown to provide relief for moderate to severe chronic pain, many are associated with high incidences of side effects, which can cause patients to discontinue their treatment. Research also shows that physicians are uncomfortable prescribing opioids due to these opioid-related side effects.

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.