Long-term Safety and Tolerability of Tapentadol Extended Release for the Management of Chronic Low Back Pain or Osteoarthritis Pain

Background: Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action: µ‐opioid receptor agonism and norepinephrine reuptake inhibition. This randomized, open‐label phase 3 study (ClinicalTrials.gov Identifier: NCT00361504) assessed the long‐term safety and tolerability of tapentadol extended release (ER) in patients with chronic knee or hip osteoarthritis pain or low back pain. Methods: Patients were randomized 4:1 to receive controlled, adjustable, oral, twice‐daily doses of tapentadol ER (100 to 250 mg) or oxycodone HCl controlled release (CR; 20 to 50 mg) for up to 1 year. Efficacy evaluations included assessments at each study visit of average pain intensity (11‐point numerical rating scale) over the preceding 24 hours. Treatment‐emergent adverse events (TEAEs) and discontinuations were monitored throughout the study. Results: A total of 1,117 patients received at least 1 dose of study drug. Mean (standard error) pain intensity scores in the tapentadol ER and oxycodone CR groups, respectively, were 7.6 (0.05) and 7.6 (0.11) at baseline and decreased to 4.4 (0.09) and 4.5 (0.17) at endpoint. The overall incidence of TEAEs was 85.7% in the tapentadol ER group and 90.6% in the oxycodone CR group. In the tapentadol ER and oxycodone CR groups, respectively, TEAEs led to discontinuation in 22.1% and 36.8% of patients; gastrointestinal TEAEs led to discontinuation in 8.6% and 21.5% of patients. Conclusion: Tapentadol ER (100 to 250 mg bid) was associated with better gastrointestinal tolerability than oxycodone HCl CR (20 to 50 mg bid) and provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis or low back pain for up to 1 year.