BACKGROUND:Tapentadol has demonstrated analgesic efficacy across a range of pain conditions. OBJECTIVE: In a head-to-head study of up to 10 days in duration, the analgesic efficacy and tolerability of tapentadol immediate release (IR) versus oxycodone IR using a flexible dosing regimen were compared in patients with acute low back pain (LBP) and associated radicular leg pain. STUDY DESIGN: Randomized (1: 1), double-blind, parallel-group study (NCT00986180). Independent Ethics Committee/Institutional Review Board approval of the protocol was obtained. SETTING:Ninety US outpatient treatment centers. METHODS:Patients with moderate to severe, acute LBP received tapentadol IR (50, 75, or 100 mg) or oxycodone HCl IR (5, 10, or 15 mg) every 4 to 6 hours as needed for pain for up to 10 days. Patients reported current pain intensity twice daily (11-point numerical rating scale). The primary efficacy endpoint was the sum of pain intensity differences (SPID) over 120 hours for LBP. Tapentadol IR was considered non-inferior to oxycodone IR if the upper bound of the 95% confidence interval (CI) for the least-squares mean (LSM) difference in SPID120 was less than 120. Secondary efficacy endpoints included 2-, 3-, and 10-day SPID for LBP; 2-, 3-, 5-, and 10-day SPID for index leg pain; 30% and 50% responder rates; patient and clinician global impressions of change; and patient satisfaction. RESULTS: The safety population included 645 patients, and the modified intent-to-treat population included 585 patients. In the tapentadol IR and oxycodone IR groups, respectively, 86.3% (277/321) and 82.7% (268/324) of patients completed the study. The most common reason for study withdrawal in both treatment groups was adverse events (tapentadol IR, 6.5% [21/321]; oxycodone IR, 7.1% [23/324]). The LSM (standard error) SPID120 for LBP was 264.6 (11.43) for tapentadol IR (n = 287) and 264.0 (11.22) for oxycodone IR (n = 298). The 95% CI for the LSM difference was -32.1 to 30.9; therefore, tapentadol IR was non-inferior to oxycodone IR for relief of LBP. No significant differences were observed between tapentadol IR and oxycodone IR for other SPID endpoints or for responder rates. At the end of the study, in the tapentadol IR and oxycodone IR treatment groups, respectively, approximately two-thirds of patients (66.2% vs 66.2%) and clinicians (67.9% vs 66.6%) rated patients' overall condition as "very much improved" or "much improved," and more than 75% of patients (79.3% vs 78.9%) were "very satisfied" or "somewhat satisfied" with their treatment. In the tapentadol IR and oxycodone IR groups, respectively, 52.3% (168/321) and 58.0% (188/324) of patients reported at least one treatment-emergent adverse event (TEAE); the most common (≥ 10%) TEAEs were vomiting (15.9% vs 24.7%), nausea (15.9% vs 20.7%), and dizziness (11.8% vs 10.5%). Vomiting (odds ratio [95% CI], 1.74 [1.17 - 2.57]) and constipation (3.43 [1.45 - 8.11]) were significantly more likely to occur in the oxycodone IR treatment group. Two (0.6%) patients in the tapentadol IR group and 3 (0.9%) patients in the oxycodone IR group experienced treatment-emergent serious adverse events. LIMITATIONS: Strict patient monitoring is generally not representative of real-world medical practice; consequently, higher incidences of TEAEs may have been reported than would be expected in a typical practice setting; it is anticipated that this bias would be similar for both treatment groups. CONCLUSIONS: This head-to-head study demonstrated that tapentadol IR had comparable analgesic efficacy and overall safety to that of oxycodone IR for the relief of moderate to severe, acute LBP and associated radicular leg pain when using flexible dosing regimens that reflect typical use in clinical practice; however, tapentadol IR demonstrated a better gastrointestinal tolerability profile, particularly for the common opioid-related TEAEs of vomiting and constipation. CLINICAL TRIAL REGISTRATION: NCT00986180.
RCT Entities:
BACKGROUND:Tapentadol has demonstrated analgesic efficacy across a range of pain conditions. OBJECTIVE: In a head-to-head study of up to 10 days in duration, the analgesic efficacy and tolerability of tapentadol immediate release (IR) versus oxycodone IR using a flexible dosing regimen were compared in patients with acute low back pain (LBP) and associated radicular leg pain. STUDY DESIGN: Randomized (1: 1), double-blind, parallel-group study (NCT00986180). Independent Ethics Committee/Institutional Review Board approval of the protocol was obtained. SETTING: Ninety US outpatient treatment centers. METHODS:Patients with moderate to severe, acute LBP received tapentadol IR (50, 75, or 100 mg) or oxycodoneHCl IR (5, 10, or 15 mg) every 4 to 6 hours as needed for pain for up to 10 days. Patients reported current pain intensity twice daily (11-point numerical rating scale). The primary efficacy endpoint was the sum of pain intensity differences (SPID) over 120 hours for LBP. Tapentadol IR was considered non-inferior to oxycodone IR if the upper bound of the 95% confidence interval (CI) for the least-squares mean (LSM) difference in SPID120 was less than 120. Secondary efficacy endpoints included 2-, 3-, and 10-day SPID for LBP; 2-, 3-, 5-, and 10-day SPID for index leg pain; 30% and 50% responder rates; patient and clinician global impressions of change; and patient satisfaction. RESULTS: The safety population included 645 patients, and the modified intent-to-treat population included 585 patients. In the tapentadol IR and oxycodone IR groups, respectively, 86.3% (277/321) and 82.7% (268/324) of patients completed the study. The most common reason for study withdrawal in both treatment groups was adverse events (tapentadol IR, 6.5% [21/321]; oxycodone IR, 7.1% [23/324]). The LSM (standard error) SPID120 for LBP was 264.6 (11.43) for tapentadol IR (n = 287) and 264.0 (11.22) for oxycodone IR (n = 298). The 95% CI for the LSM difference was -32.1 to 30.9; therefore, tapentadol IR was non-inferior to oxycodone IR for relief of LBP. No significant differences were observed between tapentadol IR and oxycodone IR for other SPID endpoints or for responder rates. At the end of the study, in the tapentadol IR and oxycodone IR treatment groups, respectively, approximately two-thirds of patients (66.2% vs 66.2%) and clinicians (67.9% vs 66.6%) rated patients' overall condition as "very much improved" or "much improved," and more than 75% of patients (79.3% vs 78.9%) were "very satisfied" or "somewhat satisfied" with their treatment. In the tapentadol IR and oxycodone IR groups, respectively, 52.3% (168/321) and 58.0% (188/324) of patients reported at least one treatment-emergent adverse event (TEAE); the most common (≥ 10%) TEAEs were vomiting (15.9% vs 24.7%), nausea (15.9% vs 20.7%), and dizziness (11.8% vs 10.5%). Vomiting (odds ratio [95% CI], 1.74 [1.17 - 2.57]) and constipation (3.43 [1.45 - 8.11]) were significantly more likely to occur in the oxycodone IR treatment group. Two (0.6%) patients in the tapentadol IR group and 3 (0.9%) patients in the oxycodone IR group experienced treatment-emergent serious adverse events. LIMITATIONS: Strict patient monitoring is generally not representative of real-world medical practice; consequently, higher incidences of TEAEs may have been reported than would be expected in a typical practice setting; it is anticipated that this bias would be similar for both treatment groups. CONCLUSIONS: This head-to-head study demonstrated that tapentadol IR had comparable analgesic efficacy and overall safety to that of oxycodone IR for the relief of moderate to severe, acute LBP and associated radicular leg pain when using flexible dosing regimens that reflect typical use in clinical practice; however, tapentadol IR demonstrated a better gastrointestinal tolerability profile, particularly for the common opioid-related TEAEs of vomiting and constipation. CLINICAL TRIAL REGISTRATION: NCT00986180.