1. 2013;16;27-40Efficacy of Tapentadol ER for Managing Moderate to Severe Chronic Pain
   Clinical Trials Study
   Marc Afilalo, MD, and Bart Morlion, MD, PhD.

BACKGROUND: Chronic non–cancer-related pain affects a large proportion of the adult population and is often difficult to manage effectively. Although opioid analgesics have been used to relieve chronic pain of different etiologies, opioids are associated with a range of side effects that may reduce patient quality of life and lead to reduced compliance with treatment.Tapentadol is a centrally acting analgesic with 2 mechanisms of action, µ-opioid receptor agonism and norepinephrine reuptake inhibition, that is available in an extended-release formulation for the management of chronic pain.

OBJECTIVE: To review the efficacy of tapentadol extended release (ER) for the management of moderate to severe chronic nociceptive and neuropathic pain.

METHODS: Efficacy results are summarized for four 15-week phase 3 studies of tapentadol ER in patients with moderate to severe chronic osteoarthritis knee pain (2 studies; ClinicalTrials.gov Identifiers: NCT00421928 and NCT00486811), low back pain (NCT00449176), and pain related to diabetic peripheral neuropathy (DPN; NCT00455520); a one-year phase 3 study of tapentadol ER in patients with moderate to severe chronic osteoarthritis pain or low back pain (NCT00361504); and a pooled analysis of data from the 15-week studies in patients with osteoarthritis knee pain or low back pain. A summary of the comparative tolerability for tapentadol ER and the active comparator used in these studies, oxycodone controlled release (CR), is provided.

RESULTS: Results of these studies showed that tapentadol ER (100 - 250 mg bid) was effective for the management of moderate to severe chronic osteoarthritis knee pain, low back pain, and pain related to DPN. Tapentadol ER (100 - 250 mg bid) has been shown to provide comparable pain relief to oxycodone HCl CR (20 - 50 mg bid) for chronic osteoarthritis knee pain and low back pain over up to one year of treatment. Tapentadol ER (100 - 250 mg bid) was associated with an improved tolerability profile, particularly gastrointestinal tolerability profile, and with lower rates of treatment discontinuations and adverse event-related discontinuations compared with oxycodone HCl CR (50 - 250 mg bid) over up to one year of treatment in patients with osteoarthritis knee pain and low back pain.

LIMITATIONS: Differences in the design and duration of these phase 3 studies may limit comparisons of the efficacy results; nevertheless, this summary of efficacy results demonstrates the broad efficacy of tapentadol ER for different types of nociceptive and neuropathic pain.

CONCLUSIONS: Tapentadol ER (100 - 250 mg bid) is effective for moderate to severe osteoarthritis pain, low back pain, and pain related to DPN and provides efficacy similar to that of oxycodone HCl CR (20 - 50 mg bid) for patients with osteoarthritis and low back pain. Tapentadol ER treatment has been associated with better gastrointestinal tolerability and compliance with therapy than oxycodone CR, which suggests that tapentadol ER may be a better option for the long-term management of chronic pain.