Search

Objectives: Constipation is a common side effect of opioid therapy. Tapentadol immediate release (IR) was better tolerated than oxycodone IR in 2 clinical trials involving patients with low back or osteoarthritis pain. The objective of this study was to examine patient-reported bowel function during those trials., Methods: Bowel function was assessed during secondary post hoc analyses using: the bowel movement questionnaire (BMQ; 10-d trial); the Patient Assessment of Constipation Symptoms questionnaire (PAC-SYM; 90-day trial); and laxative use (both trials). Random effects maximum likelihood regressions were run to examine PAC-SYM data. BMQ data were analyzed using 1-way analyses of variance and a multinomial logistic regression. Rates of laxative use were compared using χ(2) statistics., Results: The 10- and 90-day trials consistently showed that tapentadol IR caused less impairment of bowel function than oxycodone IR. BMQ data were comparable between patients receiving tapentadol IR and placebo, and better versus oxycodone IR including: lower proportion of days where bowel movement was absent (P<0.05); lower risks of reporting hard stools (P<0.001); and moderate or severe straining (P<0.001). All PAC-SYM summary scores (abdominal, rectal, stool, overall) indicated fewer symptoms among patients receiving tapentadol IR versus oxycodone IR (P<0.001). In both trials, rates of laxative use was lower for tapentadol IR treatment groups versus oxycodone IR (P<0.001)., Discussion: Patient-reported bowel function associated with tapentadol IR treatment was similar to that associated with placebo (10-d trial) and significantly better than that associated with oxycodone IR treatment (10- and 90-d trials).

Purpose: To understand the relationship between the risk of opioid-related gastrointestinal adverse effects (AEs) and exposure to tapentadol and oxycodone as well as its active metabolite, oxymorphone, using pharmacokinetic/pharmacodynamic models., Methods: The analysis was based on a study in patients with moderate-to-severe pain following bunionectomy. Population PK modeling was conducted to estimate population PK parameters for tapentadol, oxycodone, and oxymorphone. Time to AEs was analyzed using Cox proportional-hazards models., Results: Risk of nausea, vomiting, and constipation significantly increased with exposure to tapentadol or oxycodone/oxymorphone. However, elevated risk per drug exposure of AEs for tapentadol was ~3-4 times lower than that of oxycodone, while elevated AE risk per drug exposure of oxycodone was ~60 times lower than that for oxymorphone, consistent with reported in vitro receptor binding affinities for these compounds. Simulations show that AE incidence following administration of tapentadol IR is lower than that following oxycodone IR intake within the investigated range of analgesic noninferiority dose ratios., Conclusions: This PK/PD analysis supports the clinical findings of reduced nausea, vomiting and constipation reported by patients treated with tapentadol, compared to patients treated with oxycodone.

Introduction: Two randomized, double-blind, placebo-controlled studies in acute and chronic pain treatment, powered to assess noninferiority of the efficacy of tapentadol immediate release (IR) (50 mg, 75 mg) versus oxycodone hydrochloride (HCl) IR (10 mg), established comparable efficacy of tapentadol IR with oxycodone HCl IR, and suggested tapentadol IR's improved gastrointestinal tolerability. The impact of these equianalgesic doses of tapentadol and oxycodone HCl on bowel function and gastrointestinal tolerability was then directly assessed in the current study, using a validated bowel function diary to comprehensively assess opioid-induced constipation symptoms and outcomes., Methods: In this double-blind study, patients with end-stage joint disease were randomized to tapentadol IR (50 mg or 75 mg), oxycodone HCl IR 10 mg, or placebo. Treatment with IR formulations (14 days) was followed by treatment (28 days) with extended-release (ER) formulations of active drugs (or placebo)., Results: Oxycodone HCl IR treatment significantly decreased (P<0.001) mean (SD) number of spontaneous bowel movements over the 14-day period (average per week: [6.7 (5.44)] versus tapentadol IR 50 mg [9.0 (4.04)], tapentadol IR 75 mg [8.6 (4.65)], and placebo [9.9 (5.16)]) (primary measure), confirming the tolerability findings of the earlier studies. Additionally, incidences of nausea and vomiting were significantly lower over the 14-day period (nominal P<0.001) for tapentadol IR 50 and 75 mg, versus oxycodone HCl IR 10 mg. Results with ER formulations of tapentadol and oxycodone HCl over a longer treatment period were consistent with those of IR formulations., Conclusion: Tapentadol IR (50 mg, 75 mg) consistently demonstrated superior gastrointestinal tolerability, including for the most commonly reported events, such as nausea, vomiting, and constipation at doses that provide comparable efficacy with oxycodone HCl IR 10 mg. These findings validate and extend the tolerability findings of the two earlier studies that established comparable efficacy of these tapentadol and oxycodone HCl doses.

Objective: Painful diabetic peripheral neuropathy (DPN) may not be adequately managed with available therapeutic options. This phase III, randomized-withdrawal, placebo-controlled trial evaluated the safety and efficacy of tapentadol extended release (ER) for relieving painful DPN., Research Design and Methods: Patients (n = 588) with at least a 3-month history of opioid and/or non-opioid analgesic use for DPN, dissatisfaction with current treatment, and an average pain intensity score of at least 5 on an 11-point numerical rating scale (NRS; 0 = 'no pain,' 10 = 'pain as bad as you can imagine') were titrated to an optimal dose of tapentadol ER (100-250 mg bid) during a 3-week open-label phase. Subsequently, patients (n = 395) with at least a 1-point reduction in pain intensity were randomized 1:1 to receive placebo or the optimal fixed dose of tapentadol ER determined during the open-label phase for a 12-week double-blind phase., Clinical Trial Registration: NCT00455520., Main Outcome Measures: The primary efficacy outcome was the change in average pain intensity from randomization, determined by twice-daily NRS measurements. Safety was assessed throughout the study., Results: The least-squares mean difference between groups in the change in average pain intensity from the start of double-blind treatment to week 12 was -1.3 (95% confidence interval, -1.70 to -0.92; p < 0.001, tapentadol ER vs. placebo). A total of 60.5% (356/588) of patients reported at least a 30% improvement in pain intensity from the start to the end of the open-label titration phase; of the patients who were randomized to tapentadol ER, 53.6% (105/196) reported at least a 30% improvement from pre-titration to week 12 of the double-blind phase. The most common treatment-emergent adverse events that occurred during double-blind treatment with tapentadol ER included nausea, anxiety, diarrhea, and dizziness. Potential limitations of this study are related to the enriched enrollment randomized-withdrawal trial design, which may result in a more homogeneous patient population during double-blind treatment and may present a risk of unblinding because of changes in side effects from the open-label to the double-blind phase., Conclusions: Compared with placebo, tapentadol ER 100-250 mg bid provided a statistically significant difference in the maintenance of a clinically important improvement in pain 1 , 2 and was well-tolerated by patients with painful DPN.

Objective: To evaluate the efficacy and safety of tapentadol extended release (ER) for the management of moderate to severe chronic low back pain., Research Design: Patients (N = 981) were randomized 1:1:1 to receive tapentadol ER 100 - 250 mg b.i.d., oxycodone HCl controlled release (CR) 20 - 50 mg b.i.d., or placebo over 15 weeks (3-week titration period, 12-week maintenance period)., Main Outcome Measures: Efficacy was assessed as change from baseline in average pain intensity (11-point NRS) at week 12 of the maintenance period and throughout the maintenance period; last observation carried forward was used to impute missing pain scores. Adverse events (AEs) were monitored throughout the study., Results: Tapentadol ER significantly reduced average pain intensity versus placebo at week 12 (least squares mean difference vs placebo [95% confidence interval], -0.8 [-1.22, -0.47]; p < 0.001) and throughout the maintenance period (-0.7 [-1.06,-0.35]; p < 0.001). Oxycodone CR significantly reduced average pain intensity versus placebo at week 12 (-0.9 [-1.24,-0.49]; p < 0.001) and throughout the maintenance period (-0.8 [-1.16,-0.46]; p < 0.001). Tapentadol ER was associated with a lower incidence of treatment-emergent AEs (TEAEs) than oxycodone CR. Gastrointestinal TEAEs, including constipation, nausea, and vomiting, were among the most commonly reported TEAEs (placebo, 26.3%; tapentadol ER, 43.7%; oxycodone CR, 61.9%). The odds of experiencing constipation or the composite of nausea and/or vomiting were significantly lower with tapentadol ER than with oxycodone CR (both p < 0.001)., Conclusions: Tapentadol ER (100 - 250 mg b.i.d.) effectively relieved moderate to severe chronic low back pain over 15 weeks and had better gastrointestinal tolerability than oxycodone HCl CR (20 - 50 mg b.i.d.).

Introduction: This pooled analysis of data from three phase 3 studies in patients with chronic osteoarthritis knee or low back pain evaluated the efficacy and tolerability of tapentadol prolonged release (PR; 100-250 mg twice daily) compared with placebo and oxycodone hydrochloride (HCl) controlled release (CR; 20-50 mg twice daily)., Methods: Patients in each study were randomized to receive twice-daily doses of placebo, tapentadol PR (100-250 mg), or oxycodone HCl CR (20-50 mg) for a 12-week maintenance period, preceded by a 3-week titration period. Primary endpoints were change from baseline in average pain intensity (11-point numeric rating scale) at week 12 of the maintenance period and for the overall maintenance period using last observation carried forward for imputation of values missing after treatment discontinuation., Results: A total of 2968 patients were evaluated for efficacy; 2974 patients were evaluated for safety. Compared with placebo, treatment with tapentadol PR or oxycodone CR resulted in significantly greater reductions in pain intensity from baseline at week 12 and for the overall maintenance period (all P<0.001). For both primary endpoints, the efficacy of tapentadol PR was noninferior to oxycodone CR (P<0.001), and tapentadol PR had superior gastrointestinal tolerability compared with oxycodone CR (P<0.001). Results of analyses of responders, patient global impression of change, Short Form-36 domains (except general health), and the EuroQol 5-Dimension health status index were significantly better for tapentadol PR than oxycodone CR (all P

Objective: To examine discontinuations due to nausea and/or vomiting or constipation with tapentadol immediate release (IR) or oxycodone IR treatment., Design: Post hoc analyses of a 90-day, phase 3, randomized, double-blind, flexible-dose study., Setting: United States, Canada, United Kingdom., Patients: Adults with moderate to severe low back or osteoarthritis (OA) pain for > or =3 months., Interventions: Tapentadol IR 50 or 100 mg or oxycodone HCI IR 10 or 15 mg every 4-6 hours as needed., Main Outcome Measures: Adverse events and discontinuations were recorded., Results: Post hoc analyses included data from 679 patients receiving tapentadol IR and 170 receiving oxycodone IR (4:1 randomization). Tapentadol IR 50 or 100 mg and oxycodone HCI IR 10 or 15 mg provided similar levels of pain relief Overall, 21.2 percent of patients receiving tapentadol IR discontinued treatment for adverse events versus 31.2 percent of patients receiving oxycodone IR. The percentage of patients who discontinued for nausea and/or vomiting was significantly lower with tapentadol IR (5.9 percent) than oxycodone IR (14.7 percent; p = 0.0003); patients treated with oxycodone IR discontinued because of nausea and/or vomiting significantly earlier than with tapentadol IR (p < 0.0001). The percentage of patients who discontinued because of constipation was significantly lower with tapentadol IR (1.5 percent) than with oxycodone IR (5.9 percent; p = 0.0023); patients treated with oxycodone IR discontinued because of constipation significantly earlier versus tapentadol IR (p = 0.0003)., Conclusions: A lower percentage of patients discontinued because of nausea and/or vomiting or constipation with tapentadol IR versus oxycodone IR while receiving comparable pain relief suggesting tapentadol may improve the management of low back and OA pain.

Background: Tapentadol is a novel, centrally acting analgesic with mu-opioid receptor agonist and norepinephrine reuptake inhibitor activity., Objective: to evaluate the efficacy and safety of Tapentadol extended release (ER) compared with oxycodone controlled release (CR) for management of moderate to severe chronic osteoarthritis-related knee pain., Methods: this was a randomized, double-blind, active- and placebo-controlled, parallel-arm, multicentre, phase III study during which patients received Tapentadol ER, oxycodone CR or placebo for a 3-week titration period followed by a 12-week maintenance period. The study was carried out at sites in Australia, Canada, New Zealand and the US. A total of 1030 patients with chronic osteoarthritis-related knee pain were randomized to receive Tapentadol ER 100-250 mg twice daily, oxycodone HCl CR 20-50 mg twice daily or placebo. Primary endpoints (as determined prior to initiation of the study) were the changes from baseline in average daily pain intensity (rated by patients on an 11-point numerical rating scale) over the last week of maintenance and over the entire 12-week maintenance period; last observation carried forward was used to impute missing values after early treatment discontinuation., Results: efficacy and safety were evaluated for 1023 patients. Tapentadol ER significantly reduced average pain intensity from baseline to week 12 of the maintenance period versus placebo (least squares mean [LSM] difference [95% CI], -0.7 [-1.04, -0.33]), and throughout the maintenance period (-0.7 [-1.00, -0.33]). Oxycodone CR significantly reduced average pain intensity from baseline throughout the maintenance period versus placebo (LSM difference [95% CI], -0.3 [-0.67, -0.00]) but not at week 12 (-0.3 [-0.68, 0.02]). A significantly higher percentage of patients achieved > or =50% improvement in pain intensity in the Tapentadol ER group (32.0% [110/344]) compared with the placebo group (24.3% [82/337]; p = 0.027), indicating a clinically significant improvement in pain intensity, while a significantly lower percentage of patients achieved > or =50% improvement in pain intensity in the oxycodone CR group (17.3% [59/342]; p = 0.023 vs placebo). In the placebo, Tapentadol ER and oxycodone CR groups, respectively, 61.1% (206/337), 75.9% (261/344) and 87.4% (299/342) of patients reported at least one treatment-emergent adverse event (TEAE); incidences of gastrointestinal-related TEAEs were 26.1% (88/337), 43.0% (148/344) and 67.3% (230/342)., Conclusion: treatment with Tapentadol ER 100-250 mg twice daily or oxycodone HCl CR 20-50 mg twice daily was effective for the management of moderate to severe chronic osteoarthritis-related knee pain, with substantially lower incidences of gastrointestinal-related TEAEs associated with treatment with Tapentadol ER than with oxycodone CR.

Background: Tapentadol, a novel, centrally acting analgesic with 2 mechanisms of action (mu-opioid receptor agonism and norepinephrine reuptake inhibition), has been developed in an immediate-release (IR) and an extended-release (ER) formulation. Determination of the safety and equianalgesic ratios for conversion between formulations is important for physicians with patients taking tapentadol IR who may want to switch to tapentadol ER, or vice versa, for any reason., Objectives: To test whether the total daily dose (TDD) of tapentadol IR may be directly converted into a comparable TDD of tapentadol ER, and vice versa, with equivalent efficacy and comparable safety., Study Design: Randomized, double-blind, 2-period (2 weeks each) crossover study., Setting: Study centers (N = 13) in the United States., Methods: Patients with moderate to severe chronic low back pain received tapentadol IR 50, 75, or 100 mg every 4 or 6 hours (maximum TDD, 500 mg) during the 3-week open-label period to identify an optimal, stable dose of tapentadol IR for each patient. Patients were then randomized in a 1:1 ratio to receive, during the first 2-week double-blind period, either the optimal dose of tapentadol IR identified during the open-label period or a TDD of tapentadol ER (100, 150, 200, or 250 mg bid) that was as close as possible to the TDD of tapentadol IR from the open-label period. During a subsequent, 2-week double-blind period, patients received whichever formulation was not received during the first double-blind period. The primary endpoint was the mean average daily pain intensity (on an 11-point numerical rating scale) during the last 3 days of each double-blind treatment period. If the 95% confidence intervals (CIs) of the least squares mean difference between formulations were within the range of -2 to 2, the formulations were considered equivalent., Results: Of the 88 patients who were randomized, 72 completed both double-blind treatments, and 60 were included in the per-protocol analysis. The mean (standard deviation [SD]) pain intensity score decreased from 7.3 (1.19) pre-treatment to 4.2 (2.13) after 3 weeks of open-label treatment with tapentadol IR and remained constant throughout double-blind treatment (3.9 or 4.0 each week) for both formulations. The mean (SD) of the average pain intensity scores over the last 3 days of double-blind treatment was 3.9 (2.17) with tapentadol IR and 4.0 (2.29) with tapentadol ER, for an estimated difference of 0.1 (95% CI, -0.09 to 0.28). For both tapentadol IR and tapentadol ER, the median TDD administered was 300.0 mg, and acetaminophen was used by 39.5% and 45.2% of patients, respectively. The incidence of treatment-emergent adverse events during double-blind treatment was similar between the tapentadol IR and tapentadol ER groups., Limitations: Use of rescue medication theoretically could have influenced pain measurements, but in practice, pain measurements did not differ between treatments., Conclusions: Approximately equivalent TDDs of tapentadol IR and tapentadol ER provided equivalent analgesic efficacy for the relief of moderate to severe chronic low back pain and were similarly well tolerated, allowing for direct conversion between the 2 formulations., Clinical Trial Registration: NCT00594516.

Tapentadol exerts its analgesic effects through micro opioid receptor agonism and noradrenaline reuptake inhibition in the central nervous system. Preclinical studies demonstrated that tapentadol is effective in a broad range of pain models, including nociceptive, inflammatory, visceral, mono- and polyneuropathic models. Moreover, clinical studies showed that tapentadol effectively relieves moderate to severe pain in various pain care settings. In addition, it was reported to be associated with significantly fewer treatment discontinuations due to a significantly lower incidence of gastrointestinal-related adverse events compared with equivalent doses of oxycodone. The combination of these reduced treatment discontinuation rates and tapentadol efficacy for the relief of moderate to severe nociceptive and neuropathic pain may offer an improvement in pain therapy by increasing patient compliance with their treatment regimen., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

Objective: To evaluate the relative efficacy and tolerability of tapentadol immediate release (IR) and oxycodone IR for management of moderate to severe pain following orthopedic surgery (bunionectomy)., Methods: Randomized patients (N = 901) received oral tapentadol IR 50 or 75 mg, oxycodone HCl IR 10 mg, or placebo every 4-6 h over a 72-h period following surgery. Acetaminophen (< or =2 g) was allowed in the first 12 h after the first dose of study drug. In the primary analysis, tapentadol IR (50 and 75 mg) was evaluated for efficacy superior to placebo and non-inferior to oxycodone HCl IR 10 mg (using sum of pain intensity difference [SPID] over 48 h), and tolerability superior to oxycodone IR (using incidence of treatment-emergent adverse events [TEAEs] of nausea and/or vomiting)., Results: Statistically significantly higher mean SPID(48) values were observed with tapentadol IR (50 and 75 mg) and oxycodone HCl IR 10 mg than placebo (all p < 0.001). The efficacy of tapentadol IR 50 mg and 75 mg was non-inferior to oxycodone HCl IR 10 mg. The incidence of TEAEs of nausea and/or vomiting was statistically significantly lower with tapentadol IR 50 mg versus oxycodone IR 10 mg (35 vs. 59%; p < 0.001). No statistically significant difference in the incidence of nausea and/or vomiting was observed between tapentadol IR 75 mg and oxycodone IR 10 mg (51 vs. 59%; p = 0.057). A possible limitation of this study was that the intense dose and patient monitoring may not represent real-world situations and may result in higher incidences of TEAEs than expected in a practice setting; this bias would be similar for all treatment groups., Conclusions: Clinically meaningful and statistically significant improvements were observed with tapentadol IR 50 mg and 75 mg compared with placebo for the relief of moderate-to-severe acute pain after orthopedic surgery. Tapentadol IR 50 mg and 75 mg were non-inferior to oxycodone HCl IR 10 mg for the treatment of acute pain based on the primary efficacy endpoint of SPID(48) and the pre-specified margin of 48 points. The incidence of nausea and/or vomiting was statistically significantly lower for tapentadol IR 50 mg and numerically lower for tapentadol IR 75 mg than for oxycodone HCl IR 10 mg.

Objective: Tapentadol is a novel, centrally acting analgesic with two mechanisms of action, mu-opioid receptor agonism and norepinephrine reuptake inhibition, in a single molecule. This phase III, randomized, double-blind, active-controlled study evaluated the tolerability of tapentadol immediate release (IR) and oxycodone IR for low back pain or osteoarthritis pain (hip or knee), using flexible dosing over 90 days., Methods: Patients (N = 878) were randomly assigned (4:1 ratio) to receive tapentadol IR (50 or 100 mg, q4-6h, p.o.) or oxycodone IR (10 or 15 mg, q4-6h, p.o.). Tapentadol IR was evaluated for tolerability over 90 days, tolerability relative to oxycodone IR, withdrawal symptoms, and pain intensity. This study was not placebo-controlled, which limited efficacy evaluations., Results: In total, 849 intent-to-treat patients received tapentadol IR (n = 679) or oxycodone IR (n = 170), and among these, 391 patients (57.6%) in the tapentadol IR group and 86 patients (50.6%) in the oxycodone IR group completed the study. Gastrointestinal events, including nausea (18.4% vs 29.4%), vomiting (16.9% vs 30.0%), and constipation (12.8% vs 27.1%), were reported by 44.2% of patients receiving tapentadol IR and 63.5% of patients receiving oxycodone IR, respectively. Nervous system events, including dizziness (18.1% vs 17.1%), headache (11.5% vs 10.0%), and somnolence (10.2% vs 9.4%), were reported by 36.7% of patients receiving tapentadol and 37.1% of patients receiving oxycodone, respectively. Odds ratios (tapentadol:oxycodone) showed that the incidences of somnolence and dizziness were similar; however, nausea, vomiting, and constipation were significantly less likely with tapentadol IR compared with oxycodone IR. The pattern of withdrawal symptoms suggests that drug tapering may not be necessary after tapentadol IR treatment of this duration. Pain intensity measurements showed similar efficacy for tapentadol and oxycodone., Conclusion: During this 90-day study, tapentadol IR was associated with improved gastrointestinal tolerability compared with oxycodone IR while providing similar pain relief. Trial registration information: NCT00364546.

Objective: This study evaluated tapentadol immediate release (IR) for pain relief following orthopedic bunionectomy surgery., Methods: This randomized, double-blind, placebo- and active-controlled, phase III study included patients with moderate-to-severe pain following bunionectomy. Randomized patients (N = 603) received tapentadol IR 50, 75, or 100 mg; oxycodone HCl IR 15 mg; or placebo orally every 4-6 hours over a 72-hour period following bunionectomy. The primary endpoint was the sum of pain intensity difference (SPID) over 48 hours. Secondary endpoints included SPID over 12, 24, and 72 hours; total pain relief, and sum of total pain relief and sum of pain intensity difference (SPRID) over 12, 24, 48, and 72 hours; use of rescue medication; patient global impression of change; and onset of action assessment. Possible limitations of this study were that the intense dose monitoring and thorough nursing care were unlikely to represent actual use situations and could introduce similar bias across all treatment groups., Clinical Trial Registration: NCT00364247., Results: Mean SPID(48) values were significantly higher for tapentadol IR (50, 75, and 100 mg) and oxycodone HCl IR 15 mg compared with placebo (all p

Objective: Tapentadol is a new, centrally acting analgesic with two mechanisms of action, combining μ-opioid agonism and norepinephrine reuptake inhibition in a single molecule. This study assessed tapentadol immediate release (IR) in patients with postsurgical orthopedic pain., Methods: This randomized, double-blind, phase II study involved patients with moderate-to-severe pain after bunionectomy surgery (first metatarsal with osteotomy). Patients (N = 269) were randomly assigned to receive tapentadol IR 50 or 100 mg, oxycodone HCl IR 10 mg, or placebo; the study drug was taken every 4-6 h, over a 72-h period starting 1 day after surgery (Evaluation Day 2). The primary endpoint was the sum of pain intensity over 24 h (SPI-24) on the second day after randomization (Evaluation Day 3). Potential limitations of this study included the use of rescue medication and the fact that it was not powered to statistically compare between-group differences in tolerability measures., Results: Mean (standard deviation [SD]) SPI-24 values on Evaluation Day 3 were significantly lower for tapentadol IR (50 mg: 33.6 [19.7], p = 0.0133; 100 mg: 29.2 [15.2], p = 0.0001) and oxycodone HCl IR 10 mg (35.7 [17.2]; nominal p = 0.0365) compared with placebo (41.9 [17.7]). The most common treatment-emergent adverse events for all treatment groups were characteristic of drugs with μ-opioid agonist activity. While providing similar analgesic efficacy, tapentadol IR 50 mg was associated with lower rates of nausea (46.3% vs. 71.6% for oxycodone HCl IR 10 mg), dizziness (32.8% vs. 56.7%), vomiting (16.4% vs. 38.8%), and constipation (6.0% vs. 17.9%), and a similar rate of somnolence (28.4% vs. 26.9%) compared with oxycodone HCl IR 10 mg., Conclusions: Tapentadol IR 50 and 100 mg and oxycodone HCl IR 10 mg were effective in this study for the relief of acute postoperative pain following bunionectomy. The study results suggest improved gastrointestinal tolerability of tapentadol IR 50 mg compared with oxycodone at a dose showing comparable efficacy.

Objective: Tapentadol is a new, centrally acting analgesic with two mechanisms of action, combining μ-opioid agonism and norepinephrine reuptake inhibition in a single molecule. This study assessed tapentadol immediate release (IR) in patients with postsurgical orthopedic pain.Methods: This randomized, double-blind, phase II study involved patients with moderate-to-severe pain after bunionectomy surgery (first metatarsal with osteotomy). Patients (N = 269) were randomly assigned to receive tapentadol IR 50 or 100 mg, oxycodone HCl IR 10 mg, or placebo; the study drug was taken every 4-6 h, over a 72-h period starting 1 day after surgery (Evaluation Day 2). The primary endpoint was the sum of pain intensity over 24 h (SPI-24) on the second day after randomization (Evaluation Day 3). Potential limitations of this study included the use of rescue medication and the fact that it was not powered to statistically compare between-group differences in tolerability measures.Results: Mean (standard deviation [SD]) SPI-24 values on Evaluation Day 3 were significantly lower for tapentadol IR (50 mg: 33.6 [19.7], p = 0.0133; 100 mg: 29.2 [15.2], p = 0.0001) and oxycodone HCl IR 10 mg (35.7 [17.2]; nominal p = 0.0365) compared with placebo (41.9 [17.7]). The most common treatment-emergent adverse events for all treatment groups were characteristic of drugs with μ-opioid agonist activity. While providing similar analgesic efficacy, tapentadol IR 50 mg was associated with lower rates of nausea (46.3% vs. 71.6% for oxycodone HCl IR 10 mg), dizziness (32.8% vs. 56.7%), vomiting (16.4% vs. 38.8%), and constipation (6.0% vs. 17.9%), and a similar rate of somnolence (28.4% vs. 26.9%) compared with oxycodone HCl IR 10 mg.Conclusions: Tapentadol IR 50 and 100 mg and oxycodone HCl IR 10 mg were effective in this study for the relief of acute postoperative pain following bunionectomy. The study results suggest improved gastrointestinal tolerability of tapentadol IR 50 mg compared with oxycodone at a dose showing comparable efficacy. [ABSTRACT FROM AUTHOR]