Tapentadol - Clinical Trials

Clinical Trials

The efficacy of tapentadol compared to a placebo was demonstrated in two phase III (and one phase II) randomized, double-blind, multi-center, placebo-controlled clinical trials submitted to the United States Food and Drug Administration. The phase III trials evaluated tapentadol multiple dosing following orthopedic surgery and in late-stage osteoarthritis (OA). The phase II study evaluated single dosing of tapentadol following a dental procedure. All trials utilized a zero-to-ten-point scale for pain intensity (none to worst) and a zero-to-five-point scale for pain relief (none to complete). Patients were assessed at intervals; the sum of numerical values for these pain scales were the basis of evaluating efficacy. Secondary endpoints of total pain relief from baseline, time to pain relief, time to first rescue medication and the need for rescue medication are clinically relevant endpoints. These published phase II and phase III studies used active control medications, including oxycodone, morphine or NSAIDs.

Tapentadol demonstrated efficacy compared with a placebo in a phase III, three-day, multiple-dosing assessment of post-surgical (bunionectomy) pain. The mean age of this patient population was 60–62 years. Participants had a post-operative baseline pain score of>4 on an 11-point scale, and were randomized to placebo, tapentadol 50 mg, 75 mg, 100 mg or oxycodone IR 15 mg. All study medications (including oxycodone) were compared to placebo and given every four to six hours. The sum of pain intensity difference (SPID) over the first 48 hours of study medication improved with all tapentadol strengths and oxycodone, compared with a placebo (p=<0.001). The percentage of patients requiring rescue medication was less for tapentadol and oxycodone, compared with a placebo (tapentadol 100 mg 10 percent, oxycodone 15 mg 9 percent, placebo 49 percent). The time to the first dose of rescue medication required was reduced with all strengths of tapentadol and oxycodone compared with a placebo (p=<0.001, no data given). Overall, more patients experienced at least a 50-percent improvement in pain from baseline levels with tapentadol and oxycodone compared with placebo (tapentadol 50, 75, 100 mg 58 percent, 56.7 percent, 70.3 percent, oxycodone 72.8 percent, placebo 30 percent, p=<0.001). Absolute risk reduction (ARR) was 40.3 percent for Tapentadol 100 mg and 42.8 percent for oxycodone. The number needed to treat (NNT) for 50-percent pain improvement at 48 hours was 3.6, 3.8 and 2.5 for tapentadol and 2.5 for oxycodone. Tapentadol was non-inferior to oxycodone IR 15 mg. Withdrawal due to adverse events was less with Tapentadol than oxycodone (NNH; Tapentadol 50, 75, 100 mg=39, 23.8, n/a, oxycodone=100).

Tapentadol was effective in a phase III, 10-day, multiple-dosing assessment of patients awaiting knee-replacement surgery from late-stage OA. All patients were at a level of pain indicating opioid analgesics. Tapentadol 50 mg, 75 mg and oxycodone IR 10 mg was compared to a placebo. The SPID at 48 hours and 5 days improved with tapentadol 50 and 75 mg and oxycodone 10 mg compared to placebo (p=<0.001). More patients experienced at least a 50-percent improvement in pain from baseline with tapentadol and oxycodone compared to placebo (tapentadol=27, 26, oxycodone=25 percent, placebo=13 percent, p=<0.01). The number of doses needed (NNT) for 50-percent pain relief was 7.1, 7.7 and 8.3 for tapentadol 50 and 75 mg doses and oxycodone. Tapentadol was non-inferior to oxycodone IR 15 mg. In this 10-day study, tapentadol had a lower incidence of discontinuation due to adverse events than oxycodone (NNH tapentadol 50,75 mg=11.2, 6.9, oxycodone=3.6). The authors also reported a lower incidence of selected gastrointestinal adverse events with tapentadol (p=<0.001).

A phase II, single-dose trial of tapentadol 25 mg-200 mg, ibuprofen 400 mg and morphine IR 60 mg was evaluated for post-surgical dental pain. This patient population was younger than in the previous two studies (18–45 years old, mean age 23). The SPID at four and eight hours improved from baseline compared to placebo with doses of tapentadol that were>75 mg (p=<0.05). The time to noticeable, clinically meaningful pain relief reported by patients was shorter for tapentadol 200 mg and ibuprofen 400 mg compared to morphine 60 mg IR (time to perceptible, meaningful pain relief: tapentadol 200 mg=0.7 hours, 1.5 hours, morphine 60 mg=0.8 hours, 2.6 hours, ibuprofen 400 mg=0.8 hours, 1.5 hours). A minimum dose of 50 mg tapentadol was necessary to achieve statistical significance for a 50-percent reduction in pain from baseline. More patients reported a 50-percent improvement in pain from baseline with each increasing dose of tapentadol. The NNT for tapentadol 50, 75, 100, 200 mg was 13, 5, 2, and 3, compared with an NNT for morphine 60 mg and ibuprofen 400 mg of 3 and 2, respectively. Ibuprofen appeared to work well compared to other medications in this model.

Non-published studies have evaluated tapentadol with oxycodone and placebo in hip-replacement surgery (terminated due to high discontinuation rates) and tapentadol with morphine and placebo in chronic tumor-related pain (terminated due to the recall of a rescue medication, impacting the study's timeline). Results of these studies are not available. Studies recruiting subjects include tapentadol, morphine and placebo in chronic tumor-related pain and tapentadol, oxycodone and placebo in post-operative shoulder-surgery and vertebral compression-fracture pain. There have been no listed clinical trials involving tramadol or NSAIDs.