Evaluation of multiday analgesia with etoricoxib in a double-blind, randomized controlled trial using the postoperative third-molar extraction dental pain model.

OBJECTIVE: To evaluate the analgesic effects of etoricoxib and comparator agents on the second and third days after oral surgery. METHODS: There were 588 patients initially randomized to placebo (n=46), etoricoxib 120 mg once daily (n=97), etoricoxib 90 mg once daily (n=191), ibuprofen 600 mg every 6 hours (n=192), and acetaminophen 600 mg/codeine 60 mg (A/C) every 6 hours (n=62) after third-molar extraction (≥2, ≥1 impacted) in a double-blind controlled trial. Patients were allowed flexible dosing on days 2 and 3; 46, 96, 190, 192, and 56 patients on placebo, etoricoxib 120 mg, etoricoxib 90 mg, ibuprofen, and A/C, respectively, continued to Day 2 of the study. Outcomes included Average and Worst Recall Pain Assessments (0 to 10 scale) and Global Assessments of Study Medication (0 to 4 scale). Rescue medication (acetaminophen 325 mg up to 4 times daily) usage was evaluated. Adverse experiences were collected and evaluated. RESULTS: Average Pain Recall scores were lower than placebo for all active treatments on Day 2 but only for etoricoxib 120 and 90 mg on Day 3. Worst Pain Recall scores were lower than placebo for only etoricoxib 120 and 90 mg on Day 2; all treatment groups were similar on day 3. Rescue medicine was used on day 2 in 57% of placebo patients, whereas use in active treatments ranged from 18% to 23%; for Day 3, rescue was used in 22% of placebo patients, whereas use in active treatments ranged from 14% to 20%. Differences in mean Patient's Global Assessment of Study Medication scores were significant for etoricoxib versus placebo (P<0.001) and for etoricoxib versus A/C (P<0.010). Nausea and vomiting were among the most common adverse events with higher frequency in the A/C group. CONCLUSIONS: Pain control was most favorable for the etoricoxib doses and ibuprofen. Global Assessments of Study Medication continued to differentiate the treatments and demonstrated greater efficacy for etoricoxib on Days 2 and 3 compared with placebo and A/C (NCT00694369).

Evaluation of the dose range of etoricoxib in an acute pain setting using the postoperative dental pain model.

OBJECTIVE: This study was conducted to evaluate the dose range of etoricoxib in acute pain using the postoperative dental pain model further. METHODS: This double-blind, randomized controlled study evaluated etoricoxib (90 and 120 mg), ibuprofen (600 mg), and acetaminophen (600 mg/codeine) (60 mg, (A/C)) in patients aged ≥ 18 years with moderate or severe pain after surgical extraction of ≥ 2 third molars (≥ 1 impacted). The patients reported pain intensity and pain relief over 24 hours. The primary efficacy endpoint was total pain relief over 6 hours (TOPAR6). Adverse events were evaluated throughout the study. RESULTS: There were 588 patients randomized to placebo (n=46),etoricoxib (90 mg (n=191)), etoricoxib (120 mg (n=97)), ibuprofen(2400 mg (n=192)), and A/C (n=62). The overall analgesic effect (TOPAR6) of etoricoxib (90, 120 mg) was significantly greater than that of placebo (P ≤ 0.001), and not inferior to that of ibuprofen; no discernible difference was observed between etoricoxib 90 and 120 mg. Both etoricoxib doses were superior to A/C (P ≤ 0.001). Etoricoxib (90 and 120 mg) and ibuprofen(2400 mg) were generally well tolerated and had a similar incidence of adverse events (AEs). A/C was associated with significantly more AEs that led to discontinuation (ie, nausea and vomiting). CONCLUSIONS: Etoricoxib (90 and 120 mg) showed similar efficacy in the postoperative dental pain model, which was noninferior to ibuprofen and superior to A/C. A higher number of tooth extractions or a higher mean impaction score may have led to a greater separation in efficacy between the 2 etoricoxib doses.

Comparison of the analgesic efficacy of concurrent ibuprofen and paracetamol with ibuprofen or paracetamol alone in the management of moderate to severe acute postoperative dental pain in adolescents and adults: a randomized, double-blind, placebo-controlled, parallel-group, single-dose, two-center, modified factorial study.

BACKGROUND: Combination analgesics may offer improved analgesic efficacy, particularly for moderate to severe pain. OBJECTIVE: This study evaluated the analgesic benefits of concurrent ibuprofen and paracetamol compared with each drug used alone in the management of acute postoperative dental pain. METHODS: Healthy patients aged 16 to 40 years undergoing surgical removal of 3 to 4 impacted molars (total impaction score > or = 9) were enrolled in this randomized, double-blind, placebo-controlled, parallel-group, single-dose, 2-center, modified factorial US study. Patients were randomly assigned in a ratio of 2:1:2:1:1 to ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 200 mg/paracetamol 500 mg, ibuprofen 400 mg, paracetamol 1000 mg, or placebo when postoperative pain reached moderate to severe intensity. The primary efficacy end point was the sum of pain relief and pain intensity differences from 0 to 8 hours (SPRID8). Several secondary end points were also measured, including total pain relief (TOTPAR), sum of pain intensity differences (SPID), and SPID on the visual analog scale (SPID VAS) at various time points. Other analgesic efficacy measures included peak effect, onset and duration of effect, and patients' overall assessment of treatment. The tolerability of study medications was assessed in terms of the frequency and nature of adverse events, which were assessed with standard questions, as well as changes from baseline in vital signs. RESULTS: A total of 234 patients were randomly assigned to treatment and included in the intent-to- treat population. The patients were predominantly female (74.4% [174/234]) and white (76.5% [179/234]); mean (SD) age was 20.8 (3.1) years and weight was 69.1 (16.5) kg. For SPRID8, the group treated with ibuprofen 400 mg/paracetamol 1000 mg had significantly better mean scores compared with ibuprofen alone (P < 0.001), paracetamol alone (P < 0.001), and ibuprofen 200 mg/paracetamol 500 mg (P = 0.02). The group taking ibuprofen 200 mg/paracetamol 500 mg achieved significantly better mean SPRID8 scores than paracetamol alone (P = 0.03), but not ibuprofen alone (P = NS). Ibuprofen 400 mg/paracetamol 1000 mg was associated with significantly better scores than was single-agent therapy for TOTPAR, SPID, and SPID VAS at all time intervals and for SPRID from 4 to 6 hours (all, P < 0.001). Pairwise comparisons found statistically significant differences in favor of all active treatments versus placebo for virtually all efficacy end points, thereby supporting assay sensitivity. Adverse events were similar across treatments; the most frequent were nausea (26.1% [61/234]), vomiting (18.8% [44/234]), headache (10.3% [24/234]), and dizziness (8.1% [19/234]). CONCLUSION: Concurrent ibuprofen and paracetamol appeared to provide significantly better analgesic efficacy compared with ibuprofen or paracetamol alone for acute postoperative dental pain in these adolescents and adults.

A randomized, double-blind, celecoxib- and placebo-controlled study of the effectiveness of CS-706 in acute postoperative dental pain.

BACKGROUND: CS-706 is a cyclooxygenase-2 (COX-2)-selective inhibitor with an in vitro selectivity ratio (COX-1:COX-2) similar to that of celecoxib. It has exhibited analgesic, anti-inflammatory, and antitumor properties in animal models. OBJECTIVES: This study evaluated the tolerability of single doses of CS-706 and compared the analgesic efficacy of CS-706 with that of celecoxib and placebo in the dental pain model. METHODS: This was a randomized, double-blind, double-dummy, active- and placebo-controlled study. Healthy male and female subjects with moderate to severe pain intensity (PI) after dental surgery were randomized ( approximately 50 per group) to receive a single oral dose of CS-706 10, 50, 100, or 200 mg; celecoxib 400 mg; or placebo. PI and pain relief (PR) were measured on categorical and visual analog scales through 24 hours after the dose. The primary efficacy variable was the time-weighted sum of PR scores at 4 hours after the dose (TOPAR4). The onset of analgesia was assessed by calculating the pain intensity difference (PID). Perceptible and meaningful pain relief were assessed using a 2-stopwatch method. RESULTS: The majority of subjects were female (62.0%) and white (59.5%). Subjects' mean (SD) age was 22.6 (3.9) years, and their mean body mass index was 25.3 (5.1) kg/m(2). All doses of CS-706 were associated with significant analgesic efficacy compared with placebo based on the primary end point, TOPAR4 (P<0.001), and on all secondary end points (P<0.05, comparisons of all CS-706 doses vs placebo) with the exception of time to 100% PR for CS-706 10 mg. Single 50-, 100-, and 200-mg doses of CS-706 also were significantly more effective than celecoxib for TOPAR4 (P=0.036, P=0.004, and P=0.006, respectively). The onset of analgesia (PID >or= 1) for all CS-706 doses occurred within 1 hour after dosing (P<0.001 vs placebo). The median duration of analgesia, measured as the time to administration of rescue medication, was significantly greater for all doses of CS-706 compared with placebo (5.7 hours for CS-706 10 mg, >24 hours for CS-706 50, 100, and 200 mg, and 1.7 hours for placebo; P<0.001 for CS-706 50, 100, and 200 mg). These data suggest that once-daily administration of CS-706 may be effective in providing relief of acute pain. The incidence of adverse events was similar among all treatment groups. Adverse events occurring in >or= 5 % of subjects in any treatment group were nausea, vomiting, dry socket, dizziness, headache, and paresthesia. CONCLUSION: Single doses of CS-706 had significant analgesic efficacy compared with celecoxib and placebo in the relief of postoperative dental pain in the healthy subjects enrolled in this study.