Perceptible Pain Relief Research Articles

The Time to Onset and Overall Analgesic Efficacy of Rofecoxib 50 mg

To determine the time to onset of analgesia of rofecoxib based on a patient-level meta-analysis of randomized, placebo-controlled, postoperative oral surgery pain studies. A search on MEDLINE and of Merck data on file was conducted to identify studies that met the inclusion criteria. Meta-analysis inclusion criteria required that patients were treated with a single oral dose of rofecoxib 50 mg when they experienced moderate or severe pain after surgical extraction of > or = 2 third molars; study design involved patient randomization, double-blinding, and matching placebo, and onset data from individual patients were available. The meta-analysis of time to onset also required that studies used the two-stopwatch method. Eleven studies fulfilled the onset criteria and included patients who received a single dose of rofecoxib 50 mg (N = 1220) or placebo (N = 483). These studies were analyzed to determine time to onset of analgesia, time to perceptible pain relief, percentage of patients achieving onset of analgesia, and duration of analgesia. Six of the 11 studies included a nonselective nonsteroidal anti-inflammatory drug (N = 303) and were included in the onset meta-analysis for comparison. The meta-analysis of overall efficacy also required that data on total pain relief scores over 8 hours were available. Over-all effectiveness of analgesia was based on analysis of 13 studies involving 1330 rofecoxib patients and 570 placebo patients on the endpoints of total pain relief scores over 8 hours and patient global assessment of response to therapy at 24 hours. Eight of the 13 studies with a nonselective nonsteroidal anti-inflammatory drug comparator (N = 391) were included for the efficacy meta-analysis. Patient demographics and baseline characteristics were similar across treatment groups in each study. Median time to onset of analgesia for rofecoxib was 34 minutes (95% CI, 31-38 minutes), significantly faster than placebo, which did not achieve onset within the 4 hours the assessment was conducted (P < 0.001). Duration of analgesia for rofecoxib 50 mg was > 24 hours. Rofecoxib achieved a greater mean total pain relief score over 8 hours than placebo (17.4 versus 4.4; P < 0.001) and a greater patient response rate on patient global assessment of response to therapy at 24 hours than placebo (73% versus 16%; P < 0.001). Outcomes were similar between the rofecoxib group and the nonselective nonsteroidal anti-inflammatory drug group. In this meta-analysis of over 1200 rofecoxib-treated patients, a single dose of rofecoxib 50 mg demonstrated a rapid onset of analgesia in approximately half an hour combined with sustained effectiveness, supporting its use as a treatment of acute pain.

TQ-1011 is superior to morphine and placebo in alleviating moderate to severe postsurgical pain

TQ-1011 is an injectable non-opioid analgesic under clinical investigation for the treatment of acute postsurgical pain. This single dose, single-center, double blind, randomized study compared the analgesic efficacy and safety of intravenous (IV) doses of TQ-1011, 50 and 100 mg, with morphine sulfate 4 mg and placebo in patients with moderate to severe postsurgical pain following third molar surgery. Each treatment was administered over 2 minutes. One hundred and thirty patients (44 M, 86 F) with moderate or severe post-surgical pain were assessed. Pain intensity (using standard categorical and visual analog scales) and pain relief (categorical only) were assessed at baseline and 12 time points over 8 hours following dosing. Times to perceptible and meaningful pain relief were measured by stopwatch and were used to determine time to onset of analgesia. The a priori primary measure of efficacy was Total Pain Relief (TOTPAR) 0–4. Secondary measures of efficacy included TOTPAR (at other time points), Sum of Pain Intensity Difference (SPID), Sum of Pain Relief Intensity Difference (SPRID), Time to First Rescue, Peak Pain Intensity Difference (PPID), Peak Pain Relief (PPR), Time to Confirmed Perceptible Pain Relief (onset) and Patient Global Evaluation. Safety was assessed during the study and at follow-up 5–10 days post-treatment by chemistry, hematology, urinalysis, vital signs and volunteered or observed adverse effects. All efficacy analyses were performed on the Intent-to-Treat population. TQ-1011 50 mg and 100 mg were well tolerated. Both doses provided rapid onset of effect (5 and 7 minutes) and significant analgesic efficacy. The TOTPAR 0–4 for TQ-1011 50 mg, 100 mg, morphine 4 mg and placebo were 10.6, 11.6, 2.7 and 2.8, respectively. On every measure of efficacy, TQ-1011 50 mg and 100 mg IV were superior to IV morphine 4 mg and placebo (p<0.001). This research was sponsored by TheraQuest Biosciences.

Lumiracoxib in the treatment of osteoarthritis, rheumatoid arthritis and acute postoperative dental pain: results of three dose-response studies

ABSTRACTObjectives: Overview of three dose-response studies demonstrating the efficacy of lumiracoxib, a novel COX-2 selective inhibitor, for chronic pain associated with osteoarthritis (OA), or rheumatoid arthritis (RA) and acute pain following dental extraction.Methods: OA and RA: 4-week, randomized, placebo- and active-controlled studies of similar design. Patients (OA, n = 583; RA, n = 571) received lumiracoxib 50 mg, 100 mg or 200 mg twice daily (bid), lumiracoxib 400 mg once daily (od), diclofenac 75 mg bid or placebo. Dental: 12-h, single-center, randomized, placebo- and active-controlled study. Patients (n = 202) received single oral doses of lumiracoxib 100 mg or 400 mg, ibuprofen 400 mg or placebo.Main outcome measures: OA: pain intensity (PI) in the target joint (visual analogue scale [VAS]) and WOMAC score at Week 4; RA: overall PI (VAS) and ACR20 response at Week 4; Dental: difference (PID, categorical and VAS) score over 12 h post dose, time to onset of analgesia.Results: Throughout the OA study, all lumiracoxib doses provided superior reductions in PI versus placebo and at Week 4, all lumiracoxib doses provided efficacy similar to each other and to diclofenac. In the RA study, lumiracoxib 100 mg bid, 200 mg bid and 400 mg od were significantly better than placebo in PI at Weeks 1 and 2 (all p < 0.05) but demonstrated borderline significance at Week 4 (lumiracoxib 400 mg od, p = 0.06). In pain following dental surgery, PID scores for both lumiracoxib doses were superior to placebo from 1.5 h onwards and always comparable, or superior, to ibuprofen. Lumiracoxib 400 mg had the fastest onset of analgesia, measured as median time to confirmed first perceptible pain relief using the two-stopwatch method (37.4 min, superiority versus placebo, p < 0.001). Lumiracoxib was well tolerated in all studies.Conclusions: These studies provide initial evidence that lumiracoxib is an effective, well-tolerated agent for the treatment of chronic and acute pain.

Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: A single-center, single-dose, randomized, active-controlled, parallel-group study in a dental surgery pain model

Background: The combination of tramadol and acetaminophen has demonstrated good efficacy in various clinical pain models. However, there is a need for comparisons of the onset of analgesia and other measures of analgesic efficacy with this combination and other strong combination analgesics for the management of acute pain.Objective: The goal of this study was to compare the time to onset of analgesia and other measures of analgesic efficacy with tramadol/acetaminophen 75/650 mg (Tr/Ac) and codeine/acetaminophen/ibuprofen 20/500/400 mg (Co/Ac/Ib) in the management of acute pain after oral surgery.Methods: This was a single-center, single-dose, randomized, active-controlled, parallel-group study in healthy subjects who had undergone surgical extraction of ≥1 impacted third molar requiring bone removal. When patients reported at least moderate pain after dental surgery (score ≥5 on a 10-point scale), they were randomized to 1 of 2 treatment groups. The time to onset of analgesia was measured using a 2-stopwatch technique. The time to the onset of perceptible and meaningful pain relief, pain intensity, pain relief, patient's overall assessment, and adverse events were recorded for 6 hours after dosing.Results: One hundred twenty-eight subjects participated in the study, 64 in each treatment group. The 2 groups were similar in terms of baseine pain severity and demographic characteristics (mean age, 23.7 and 23.4 years in the Tr/Ac and Co/Ac/Ib groups, respectively; mean body weight, 58.5 and 60.3 kg). The median times to the onset of perceptible pain relief were a respective 21.0 and 24.4 minutes, and the median times to the onset of meaningful pain relief were 56.4 and 57.3 minutes. Mean total pain relief and the sum of pain intensity difference were also similar in the early period after dosing (0–4 hours). However, between 4 and 6 hours, Co/Ac/Ib was associated with significant differences in both variables compared with Tr/Ac (P < 0.05). Although similar through the 4-hour assessment, mean pain intensity difference was significantly greater with Co/Ac/Ib at 5 to 6 hours. The proportion of patients assessing their assigned treatment as good or better was significantly greater with Co/Ac/Ib compared with Tr/Ac (P < 0.05). The safety profile of Tr/Ac was comparable to that of Co/Ac/Ib.Conclusions: In this small and selected group of subjects, the onset of analgesia and analgesic efficacy of Tr/Ac was comparable to that of Co/Ac/Ib. Tr/Ac provided rapid and effective analgesia for acute postoperative dental pain in this population.

NSAIDs and acetaminophen: Comparison of opioid rescue use between Rofecoxib and Oxycodone/Acetaminophen in a double-blind, randomized trial of patients with acute pain

The selective cyclooxygenase (COX)-2 inhibitors, rofecoxib (ROF) and valdecoxib (VAL), have demonstrated efficacy comparable to NSAIDs in various pain models. This study compared the analgesic efficacy of single doses of ROF 50 mg (approved acute pain dose) with VAL 40 mg (twice the maximum approved dose) in postoperative dental pain. This randomized, double-blind study enrolled 125 patients to treatment with single doses of ROF 50 mg (N=51), VAL 40 mg (N=50), or placebo (N=24). Patient pain intensity and pain relief were assessed at 16 prespecified time points over 24 hours using standard scales. The primary endpoint was total pain relief over 12 hours (TOPAR12). Other measurements included patient global assessment at 12 hours, median time to confirmed perceptible pain relief (onset of analgesia), peak pain relief (peak analgesic effect), and median time to rescue medication (duration of effect). Baseline characteristics among the groups were similar. TOPAR12 scores (range 0-48) were similar (p=0.574) between ROF (27.0) and VAL (28.6). ROF and VAL, respectively, provided a similar responder rates on patient global assessment at 12 hours (76% vs 74%) and peak pain relief (3.1 vs. 3.0, range 0-4). Onset of analgesia was similar (<45 minutes) and was achieved by 78% of ROF and 74% of VAL patients. Analgesia duration was also similar (>24hrs). Improvement on all endpoints with active treatments compared to placebo were significant (p<0.001). Incidence of adverse experiences was 35% with ROF compared to 50% for VAL (NS). Adverse experience incidence compared to placebo (71%) was significantly less with ROF (p<0.01), but not with VAL. Placebo events were likely attributable to rescue medication. ROF 50 mg and VAL 40 mg provide similar analgesic effect in postsurgical dental pain setting and were generally well-tolerated.

Perioperative pain: other: VIOXX (rofecoxib) sustains effectiveness in treatment of postoperative bunionectomy pain

Rofecoxib has demonstrated efficacy in the treatment of acute pain. In this study we assessed the analgesic effect of once daily rofecoxib 50 mg versus placebo over 5 days in the treatment of postoperative bunionectomy pain. Patients who had undergone first metatarsal bunionectomy (with osteotomy) were eligible for this double-blind, placebo-controlled, randomized study. Approximately 24 hours after surgery patients experiencing moderate or severe pain were randomly allocated to receive rofecoxib (N=27) or placebo (N=26). Patients recorded pain intensity, pain relief, and global evaluations at prespecified timepoints during the 24-hour postdose period. The overall analgesic effect was determined as the total pain relief over 8 hours (TOPAR8), the primary endpoint. Time to onset (two-stopwatch method) and duration (time to rescue medication) were also determined. On Days 2-5, patients took study medication once daily in the morning, and recorded (at bedtime) a global evaluation, the daily “worst”, “least”, and “average” pain, and the number of tablets of acetaminophen/hydrocodone (500/7.5 mg) used. Compared to placebo, rofecoxib 50 mg provided significant (p<0.050) pain relief as assessed by the overall analgesic effect (TOPAR8) and patient's global evaluation. Median time to onset (confirmed perceptible pain relief) was shorter for rofecoxib 50 mg (35 min) compared to placebo (>4 hrs) (p=0.058). On Days 2 to 5, rofecoxib provided superior analgesic effect to placebo as assessed by patient's global evaluation score (p=0.003) and a trend in reduction of the rescue (opioid) medication use (p=0.105). In addition, the rofecoxib patients reported “worst” and “average” pain that trended to be less than that of the placebo patients (p=0.147 and p=0.099, respectively). Both groups reported similar “least” pain. Rofecoxib was generally well tolerated. Rofecoxib 50 mg once daily for 5 days, provided pain relief to patients with postoperative bunionectomy pain.

NSAIDs and acetaminophen: Comparison of analgesic efficacy of rofecoxib 50 mg between patients with moderate pain and severe acute pain

Rofecoxib 50 mg is effective in the treatment of acute pain. A recently completed study compared patient responses to rofecoxib (ROF) and multidose oxycodone/acetaminophen (OXY/ACET) using a validated postoperative dental pain model. We further compared the response to ROF treatment between patients with moderate pain and severe pain in this double-blind, randomized control trial. Patients experiencing moderate or severe pain after surgical extraction of at least 2 third molars were randomized to a single dose of ROF 50mg (N=118), OXY/ACET 10/650mg followed by 5/325mg q6hrs PRN (N=122), or placebo (N=30) for 24hrs. Key endpoints were overall analgesic efficacy over 6hrs (TOPAR6) and 24hrs (SPID24). To compare responses to ROF between patients with moderate and severe pain, TOPAR6, SPID24, patient global responders, onset (time to confirmed perceptible pain relief), and duration (time to rescue medication within) were analyzed for consistency of treatment effect by baseline pain intensity subgroups. ROF demonstrated comparable overall efficacy to OXY/ACET on TOPAR6 and SPID24. ROF patients with moderate and severe pain achieved numerically similar responses on TOPAR6 and SPID24, which were comparable to moderate and severe pain subgroup responses with OXY/ACET. Patient global response was also numerically similar between ROF patients with moderate and severe pain at 6hrs (82.4% vs 78.7%) and at 24hrs (84.5% vs 78.7%) with similar treatment effects among the moderate and severe subgroups compared to OXY/ACET. ROF patients in the moderate and severe subgroups achieved pain relief in a similar timeframe (38 vs 39 minutes); the proportion of patients achieving onset was also similar (84.5% vs 80.9%). The duration of analgesia for ROF was >24hrs for both subgroups. Rofecoxib 50 mg has similar analgesic efficacy in patients with severe acute postoperative dental pain and moderate pain, based on overall analgesic effect, onset, and duration.

NSAIDs and acetaminophen: Analgesic effect of rofecoxib 50 mg and valdecoxib 40 mg on postoperative pain: a randomized, placebo-controlled study

The selective cyclooxygenase (COX)-2 inhibitors, rofecoxib (ROF) and valdecoxib (VAL), have demonstrated efficacy comparable to NSAIDs in various pain models. This study compared the analgesic efficacy of single doses of ROF 50 mg (approved acute pain dose) with VAL 40 mg (twice the maximum approved dose) in postoperative dental pain. This randomized, double-blind study enrolled 125 patients to treatment with single doses of ROF 50 mg (N=51), VAL 40 mg (N=50), or placebo (N=24). Patient pain intensity and pain relief were assessed at 16 prespecified time points over 24 hours using standard scales. The primary endpoint was total pain relief over 12 hours (TOPAR12). Other measurements included patient global assessment at 12 hours, median time to confirmed perceptible pain relief (onset of analgesia), peak pain relief (peak analgesic effect), and median time to rescue medication (duration of effect). Baseline characteristics among the groups were similar. TOPAR12 scores (range 0-48) were similar (p=0.574) between ROF (27.0) and VAL (28.6). ROF and VAL, respectively, provided a similar responder rates on patient global assessment at 12 hours (76% vs 74%) and peak pain relief (3.1 vs. 3.0, range 0-4). Onset of analgesia was similar (<45 minutes) and was achieved by 78% of ROF and 74% of VAL patients. Analgesia duration was also similar (>24hrs). Improvement on all endpoints with active treatments compared to placebo were significant (p<0.001). Incidence of adverse experiences was 35% with ROF compared to 50% for VAL (NS). Adverse experience incidence compared to placebo (71%) was significantly less with ROF (p<0.01), but not with VAL. Placebo events were likely attributable to rescue medication. ROF 50 mg and VAL 40 mg provide similar analgesic effect in postsurgical dental pain setting and were generally well-tolerated.

Onset of pain relief with rofecoxib in chronic low back pain: results of two four-week, randomized, placebo-controlled trials

SUMMARYObjective: We recently reported the efficacy of rofecoxib in two randomized controlled trials in chronic low back pain (CLBP). The objectives of this report are to present data regarding the onset of efficacy of rofecoxib from these trials and propose methods for reporting onset.Research design and methods: Patients were aged 18-75, with non-radicular CLBP for >3 months. Patients were randomized to rofecoxib 25 mg, 50 mg, or placebo once daily for 4 weeks. Assessments included Low Back Pain and Bothersomeness scales every morning and Relief from Starting Pain after the first dose at 0.5,1, 2, 3,4h, bedtime, and next morning. Onset of meaningful relief was measured by Time to Confirmed 50% Reduction in Pain and Time to Confirmed 'Slightly' or 'Not At All' Bothersome Pain. Onset of perceptible pain relief was measured by Time to At Least 'A Little' Confirmed Pain Relief.Results: 690 patients entered. Significantly more patients treated with rofecoxib had meaningful relief compared to placebo: 60.4,58.4, and 34.7% for rofecoxib 25mg, 50mg, and placebo (p < 0.001). Median time to meaningful relief for rofecoxib was 2 days, 1 day sooner than placebo. Rofecoxib was superior to placebo by bedtime after the first dose.Conclusions: Approximately 2/3 of patients achieved meaningful pain relief with rofecoxib compared with 1/3 receiving placebo. Median time to onset of meaningful relief was about 2 days, but superior relief over placebo was seen by bedtime after the first dose. Onset of perceptible pain relief was within 2 h. We propose that measures of onset of analgesic effect include the proportion of patients who achieve meaningful pain relief and in this subgroup, the time-to-onset of confirmed meaningful reduction in pain intensity, time-to-onset of confirmed pain relief, and time to first separation from placebo in the proportion of patients who achieve meaningful pain relief.

Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients

Patients with controlled background pain associated with cancer frequently also experience episodes of moderate to severe intensity breakthrough pain. Opioid pharmacotherapy, particularly with oral morphine, remains the cornerstone for the management of cancer pain. Nasal administration of opioids provides a mechanism for more rapid drug absorption and more rapid onset of pain relief compared with oral dosing. This non-randomized, open-label, uncontrolled investigation evaluated the pharmacokinetics, safety and efficacy of a single 40 mg dose of nasal morphine gluconate, administered to cancer patients in response to an episode of breakthrough pain. Single dose nasal morphine gluconate administered to 11 patients was associated with effective plasma morphine concentrations (mean C max 64 ng/ml; range 33.8–121 ng/ml) and low plasma morphine metabolites (morphine-6-glucuronide mean C max 114 ng/ml; range 46–189 ng/ml; morphine-3-glucuronide mean C max 572 ng/ml; range 257–990 ng/ml). Side effects were minor and limited to nasal irritation. Patients reported rapid onset of pain relief (perceptible pain relief achieved in 10/11 patients, time to onset 2.4±2.1 min; and meaningful pain relief, achieved in five patients, 6.8±7.3 min to onset, mean t max 0.36 h). Pain intensity scores were significantly reduced at all times after dosing; pain relief scores were unchanged. Patient satisfaction ratings were high. These results show that nasal morphine has rapid absorption and apparent onset of effect. Additional multi-dose, dose-ranging and placebo-controlled studies of nasal morphine for cancer pain are warranted.

The Cost-Effectiveness of Acetaminophen, NSAIDs, and Selective COX-2 Inhibitors in the Treatment of Symptomatic Knee Osteoarthritis

Objective The objective of this study was to conduct an economic evaluation of rofecoxib and celecoxib compared with high-dose acetaminophen or ibuprofen with and without misoprostol for patients with symptomatic knee osteoarthritis (OA). Methods A decision analysis model was designed over 6 months using two measures of effectiveness: 1) number of upper gastrointestinal (GI) adverse events averted; and 2) number of patients who achieved perceptible pain relief. Separate analyses were conducted for all patients and for those who did not respond to acetaminophen. Outcome probabilities were obtained from a comprehensive review of randomized controlled trials and observational studies. Costs were derived from actual resource utilization of OA patients. Results In terms of averting GI events, acetaminophen dominates the other options for an average risk patient population. For patients who did not respond to acetaminophen, rofecoxib had the lowest incremental cost-effectiveness ratio (ICER) per GI event avoided ($32,000) relative to ibuprofen. In terms of pain control, ibuprofen had an ICER of $610.77 per additional patient achieving minimal perceptible clinical improvement (MPCI) relative to acetaminophen, while rofecoxib had an ICER of $12,000 relative to ibuprofen. For patients who did not respond to acetaminophen and who are at high risk of developing an adverse GI event, rofecoxib dominates ibuprofen as the preferred alternative for both measures of effectiveness. One-way, two-way, and probabilistic sensitivity analyses established that these results were generally robust. Conclusions Our results suggest that for average-risk knee OA patients, acetaminophen dominates the other therapies in terms of cost per GI event averted. In terms of pain relief, cost-effectiveness acceptability curves indicate that if one values pain relief below $275 per patient achieving MPCI, acetaminophen is the therapy most likely to be optimal; between $275 and $14,150, ibuprofen is most likely to be optimal; and above $14,150, rofecoxib is most likely to be optimal.

A comparison of rofecoxib versus celecoxib in treating pain after dental surgery: A single-center, randomized, double-blind, placebo- and active-comparator-controlled, parallel-group, single-dose study using the dental impaction pain model

Background: Rofecoxib and celecoxib, selective cyclooxygenase-2 inhibitors, have analgesic efficacy similar to that of nonselective nonsteroidal anti-inflammatory drugs. Objective: This study was designed to confirm earlier findings that the overall analgesic efficacy of rofecoxib 50 mg was superior to that of celecoxib 200 mg and to extend the comparison to include celecoxib 400 mg. Methods: In this single-center, randomized, double-blind, placebo- and active-comparator-controlled, parallel-group, single-dose study, patients who experienced moderate or severe pain after surgical extraction of at least 2 third molars received a single oral dose of either rofecoxib 50 mg, celecoxib 400 mg, celecoxib 200 mg, ibuprofen 400 mg, or placebo. Patients recorded scores of pain intensity, pain relief, and global assessment at prespecified time intervals throughout the 24-hour period after dosing. The end points were total pain relief (TOPAR) score over 8 hours (TOPAR8; primary end point), TOPAR score over 12 hours (TOPAR12), sum of pain intensity difference (SPID) over 8 and 12 hours (SPID8 and SPID12), patient's global assessment of study drug at 8 hours, time to confirmed perceptible pain relief (ie, time to onset of analgesic effect), peak pain intensity difference (PID), peak pain relief, time to first dose of rescue medication (ie, duration of analgesic effect), and percentage of patients using rescue medication. Results: A total of 482 patients (358 females, 124 males; mean age, 22.1 years) were enrolled. Rofecoxib 50 mg ( n = 151 patients) demonstrated significantly greater overall analgesic efficacy compared with celecoxib 400 mg ( n = 151), as measured by TOPAR8 (least squares mean [SE] 17.2 [0.8] vs 15.0 [0.8]; P < 0.05) and TOPAR12 (25.3 [1.2] vs 21.0 [1.2]; P < 0.05), as well as a significantly longer duration of analgesic effect ( P < 0.05). Time to onset of analgesic effect and peak analgesic effect were similar for rofecoxib 50 mg and celecoxib 400 mg. Rofecoxib also showed significantly greater overall analgesic efficacy than did celecoxib 200 mg ( n = 90) including greater TOPAR8 scores (17.2 [0.8] vs 11.5 [1.1]; P < 0.001), faster onset of analgesic effect ( P < 0.001), greater peak analgesic effect ( P < 0.001 for peak pain relief and peak PID), and longer duration of analgesic effect ( P < 0.001). The overall analgesic efficacy of rofecoxib 50 mg was similar to that of ibuprofen 400 mg ( n = 45), except that the duration of analgesic effect of rofecoxib 50 mg was significantly longer ( P < 0.001). All active treatments produced significantly greater overall analgesic efficacy compared with that of placebo ( P < 0.001 for all scores [TOPAR8, TOPAR12, SPID8, SPID12, and patient's global assessment] for all study drugs). The adverse-events (AE) profile was generally similar in all treatment groups. The 3 most common AEs were nausea, postextraction alveolitis, and vomiting. Conclusions: In this study, rofecoxib 50 mg provided generally superior overall analgesic efficacy compared with that of celecoxib 400 and 200 mg, including a significantly longer duration of analgesic effect. The overall analgesic efficacy of rofecoxib 50 mg was generally similar to that of ibuprofen 400 mg, except for a significantly longer duration of analgesic effect.

Comparison of the analgesic efficacy of rofecoxib and enteric-coated diclofenac sodium in the treatment of postoperative dental pain: A randomized, placebo-controlled clinical trial

Background: Rofexocib is a selective cyclooxygenase-2 inhibitor indicated for the treatment of acute pain, with similar analgesic efficacy to ibuprofen and naproxen sodium. Diclofenac sodium is the most commonly prescribed nonsteroidal anti-inflammatory drug worldwide; it is effective for the treatment of pain as well as the signs and symptoms associated with the painful conditions of osteoarthritis and rheumatoid arthritis. Objective: The aim of this study was to compare the analgesic efficacy and tolerability of a single dose of rofexocib 50 mg, 3 doses of enteric-coated diclofenac sodium 50 mg, and placebo over 8-hour and 24-hour periods in patients with moderate to severe pain after oral surgery. Methods: In this double-blind, placebo- and active comparator-controlled, parallel-group study, patients experiencing moderate to severe pain after the surgical extraction of ≥2 third molars were randomized to receive a single dose of rofexocib 50 mg, 3 doses of enteric-coated diclofenac sodium 50 mg (50 mg given every 8 hours), or placebo. Patients rated pain intensity, pain relief, and global assessments at prespecified times throughout the 24-hour period after initial dosing. Overall analgesic efficacy was determined by total pain relief over 8 hours (TOPAR8) and 24 hours (TOPAR24) and patient global assessments at 8 and 24 hours. Onset of analgesic effect was determined by using the 2-stopwatch method for confirmed perceptible pain relief. Peak analgesic effect was the maximum pain relief attained during the first 8 hours. The duration of analgesic effect was determined by median time to rescue analgesia use. Results: A total of 305 patients were randomized to treatment: 121 received rofexocib, 121 received diclofenac sodium, and 63 received placebo. The baseline demographics were similar among the groups. Overall, 61.3% experienced moderate pain and 38.7% experienced severe pain; 53.1% were female; and the mean age was 23.4 years. The overall analgesic efficacy, as assessed by TOPAR8, of a single dose of rofecoxib 50 mg was significantly greater than a single dose of enteric-coated diclofenac sodium 50 mg (20.5 vs 8.2) and placebo (20.5 vs 5.9). Patient global assessment at 8 hours was also significantly better for rofecoxib compared with enteric-coated diclofenac sodium and placebo. TOPAR24 was significantly greater for a single dose of rofecoxib 50 mg compared with 3 doses of enteric-coated diclofenac sodium 50 mg (64.1 vs 25.1) and placebo (64.1 vs 19.2). At 24 hours, the patient global assessment for rofecoxib was significantly better than that achieved with enteric-coated diclofenac sodium and placebo. The onset of analgesic effect was significantly more rapid for rofecoxib than for enteric-coated diclofenac sodium and placebo (median times: 31 minutes, >4 hours, and >4 hours, respectively). The peak analgesic effect was significantly greater for rofecoxib compared with enteric-coated diclofenac sodium (3.2 vs 1.5) and placebo (3.2 vs 1.1). The duration of analgesia was significantly longer for rofecoxib than enteric-coated diclofenac sodium (median times: >24 hours vs 1 hour and 37 minutes) and placebo (>24 hours vs 1 hour and 37 minutes). Enteric-coated diclofenac sodium was numerically greater than placebo for the key end points measuring overall efficacy (total pain relief and patient global assessment), but diclofenac sodium did not provide as much analgesic effect as expected for a drug effective for pain, osteoarthritis, and rheumatoid arthritis and did not differ significantly from placebo. Overall, both rofecoxib and enteric-coated diclofenac sodium were generally well tolerated, although the rofecoxib group had a significantly lower incidence of clinical and drug-related adverse events than the enteric-coated diclofenac sodium group. Conclusions: A single 50-mg dose of rofecoxib provided greater overall analgesic efficacy over 8 hours, more rapid onset of analgesia, greater maximum analgesic effect, and longer duration of effect than a single 50-mg dose of enteric-coated diclofenac sodium in patients with moderate to severe pain associated with oral surgery. Compared with 3 doses of enteric-coated diclofenac sodium 50 mg (50 mg every 8 hours), a single dose of rofecoxib 50 mg provided greater overall analgesic efficacy over 24 hours.

Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double-blind, randomized, placebo- and active comparator—controlled clinical trial

Background: In recent studies of acute pain and primary dysmenorrhea, rofecoxib, a nonsteroidal anti-inflammatory drug that selectively targets the cyclooxygenase-2 enzyme, was found to be similar in efficacy to ibuprofen and naproxen sodium. Objective: The purpose of this study was to determine the analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with the combination of codeine 60 mg/acetaminophen 600 mg in a model of postsurgical dental pain. Methods: In this double-blind, placebo- and active comparator—controlled, parallel-group study, patients experiencing moderate or severe pain after the surgical extraction of ≥2 third molars, at least 1 of which was a mandibular impaction, were randomized to receive placebo, rofecoxib 50 mg, or codeine 60 mg/acetaminophen 600 mg. Patient evaluations of pain intensity, pain relief, and global assessments were recorded throughout the 24-hour period after dosing. The 2-stopwatch method was used to determine time to confirmed perceptible pain relief. The primary end point assessing overall analgesic effect was total pain relief over 6 hours (TOPAR6). Secondary end points were patient global assessment of response to therapy (PGART) at 6 hours, onset of analgesia, peak analgesic effect, and duration of analgesia. Results: A total of 393 patients were enrolled; 182 received rofecoxib, 180 received codeine/acetaminophen, and 31 received placebo. The overall analgesic effect of rofecoxib 50 mg was greater than that of codeine 60 mg/acetaminophen 600 mg for TOPAR6 (12.4 vs 7.0; P < 0.001) and PGART at 6 hours ( P < 0.001). The onset of analgesic effect was similar for rofecoxib and codeine/acetaminophen. Peak analgesic effect as measured by peak pain relief scores during the first 6 hours was significantly greater in the rofecoxib group compared with the codeine/acetaminophen group ( P < 0.001), as was the duration of analgesic effect measured by the time to rescue analgesia (9.6 hours vs 2.3 hours, P < 0.001). Adverse events were reported in 33.0%, 46.1%, and 32.3% of patients treated with rofecoxib, codeine/acetaminophen, and placebo, respectively. The most common adverse events were nausea (6.0%, 25.0%, and 9.7%, respectively) and vomiting (3.8%, 18.3%, and 6.5%, respectively). Significantly more patients in the codeine/acetaminophen group than in the rofecoxib group experienced adverse events overall ( P < 0.050) and nausea in particular ( P < 0.001). Conclusion: In this study of moderate to severe postoperative dental pain, the analgesic efficacy of rofecoxib 50 mg was greater than that of codeine/acetaminophen, with a lower incidence of adverse events and nausea.

Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions

Purpose: The purpose of this double-blind, randomized study was to compare the efficacy and safety of a single dose of the following medications: 2 tablets of Vicoprofen (ibuprofen 200 mg/hydrocodone 7.5 mg; Knoll Pharmaceutical Co, Mount Olive, NJ), 2 tablets of acetaminophen with codeine phosphate (acetaminophen 300 mg/codeine 30 mg), and 2 tablets of placebo in the management of moderate to severe postoperative dental pain after surgical extraction of at least one impacted mandibular third molar.Patients and Methods: One hundred twenty-five patients (75 women, 50 men) participated in the study. The time of first perceptible pain relief and meaningful pain relief were measured using a stopwatch technique. Pain intensity and pain relief scores were recorded using standard verbal descriptors at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, and 8 hours after dosing. At the conclusion of the study, patients completed a global evaluation for the effectiveness of the study medication.Results: Both active treatments were superior to placebo for all analgesic measures. Pain relief scores were significantly better for Vicoprofen than placebo throughout the study and significantly better than for acetaminophen with codeine from 2 through 8 hours after dosing. The duration of analgesia (time to remedication) was significantly longer for Vicoprofen (median, 5.50 hours) compared with acetaminophen with codeine (median, 3.03 hours) and placebo (median, 1.00 hours). Mean global evaluation for Vicoprofen was significantly better than for placebo and acetaminophen with codeine. Overall, there were no significant differences in the adverse event profile among the 3 treatment groups.Conclusions: Vicoprofen was found to be an effective postoperative analgesic medication in the management of acute postoperative dental pain. Its total analgesic effect, duration of analgesia, and global evaluation were superior to acetaminophen with codeine and placebo in this study model.

Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions

<h2>Abstract</h2> <b>Purpose:</b> The purpose of this double-blind, randomized study was to compare the efficacy and safety of a single dose of the following medications: 2 tablets of Vicoprofen (ibuprofen 200 mg/hydrocodone 7.5 mg; Knoll Pharmaceutical Co, Mount Olive, NJ), 2 tablets of acetaminophen with codeine phosphate (acetaminophen 300 mg/codeine 30 mg), and 2 tablets of placebo in the management of moderate to severe postoperative dental pain after surgical extraction of at least one impacted mandibular third molar. <b>Patients and Methods:</b> One hundred twenty-five patients (75 women, 50 men) participated in the study. The time of first perceptible pain relief and meaningful pain relief were measured using a stopwatch technique. Pain intensity and pain relief scores were recorded using standard verbal descriptors at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, and 8 hours after dosing. At the conclusion of the study, patients completed a global evaluation for the effectiveness of the study medication. <b>Results:</b> Both active treatments were superior to placebo for all analgesic measures. Pain relief scores were significantly better for Vicoprofen than placebo throughout the study and significantly better than for acetaminophen with codeine from 2 through 8 hours after dosing. The duration of analgesia (time to remedication) was significantly longer for Vicoprofen (median, 5.50 hours) compared with acetaminophen with codeine (median, 3.03 hours) and placebo (median, 1.00 hours). Mean global evaluation for Vicoprofen was significantly better than for placebo and acetaminophen with codeine. Overall, there were no significant differences in the adverse event profile among the 3 treatment groups. <b>Conclusions:</b> Vicoprofen was found to be an effective postoperative analgesic medication in the management of acute postoperative dental pain. Its total analgesic effect, duration of analgesia, and global evaluation were superior to acetaminophen with codeine and placebo in this study model. © 2000 American Association of Oral and Maxillofacial Surgeons