Paul Kotey

Comparison of Rofecoxib and Celecoxib, Two Cyclooxygenase-2 Inhibitors, in Postoperative Dental Pain: A Randomized, Placebo- and Active-Comparator- Controlled Clinical Trial

Pain is a common complaint, often occurring in conjunction with inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesic agents in ambulatory patients. In recent studies, the cyclooxygenase-2 (COX-2) inhibitor rofecoxib demonstrated analgesic effects similar to those of NSAIDs in the treatment of acute pain and primary dysmenorrhea. The present randomized, single-dose, double-blind, double-dummy, placebo- and active-comparator-controlled, parallel-group study was undertaken to compare the analgesic efficacy of the COX-2 inhibitors rofecoxib 50 mg and celecoxib 200 mg with that of ibuprofen 400 mg and placebo in patients with postoperative dental pain. Two hundred and seventy-two patients experiencing pain after the removal of > or =2 third molars were randomized according to pain severity (moderate vs severe) to receive a single dose of placebo (n = 45), rofecoxib 50 mg (n = 90), celecoxib 200 mg (n = 91), or ibuprofen 400 mg (n = 46). Using a patient diary, patients recorded pain intensity, pain relief, and global evaluations throughout the 24-hour period after dosing. The overall analgesic effect, onset of action, peak effect, and duration of effect were evaluated, with the primary end point being total pain relief over 8 hours (TOPAR8). The safety profile was assessed on the basis of physical findings, laboratory results, and spontaneous reports of adverse experiences. The results showed that compared with celecoxib, rofecoxib had superior analgesic effects on all measures of analgesic efficacy, including overall analgesic effect (TOPAR8, 18.3 vs. 12.5; P<0.001), time to onset of effect (30 vs. 60 minutes; P = 0.003), peak pain relief (score, 2.8 vs 2.3; P<0.05), and duration of effect (>24 vs. 5.1 hours; P<0.001). In addition, rofecoxibs analgesic efficacy was similar to that of ibuprofen (TOPAR8, 18.3 vs. 17.0; P = 0.460), but the duration was longer (P<0.05); with ibuprofen, the time to on set was 24 minutes, peak pain relief score was 2.9, and duration of analgesic effect was 8.9 hours. The safety profile was similar across all treatment groups. Thus rofecoxib provided analgesic efficacy superior to that of celecoxib and comparable to that of ibuprofen in the treatment of patients with acute postoperative dental pain.

Rofecoxib, a specific cyclooxygenase-2 inhibitor, in primary dysmenorrhea: a randomized controlled trial.

OBJECTIVE To determine whether rofecoxib is effective for treating primary dysmenorrhea and whether cyclooxygenase-2 is involved in the pathophysiology of primary dysmenorrhea. METHODS A double-masked, randomized, placebo and active-comparator-controlled clinical trial including 127 subjects with histories of primary dysmenorrhea was conducted in an outpatient clinical research center. Subjects were randomly assigned to placebo, rofecoxib 25 or 50 mg followed by 25 mg every 24 hours as needed, or naproxen sodium 550 mg every 12 hours as needed for up to 3 days. Subjects took all four treatments in a balanced, complete-block, crossover design. Measurements included self-administered questionnaires of analgesic efficacy, spontaneous reports of adverse experiences, physical examinations, and laboratory safety tests. RESULTS Rofecoxib 25 and 50 mg provided analgesic efficacy greater than placebo (P < or = .006) for the primary endpoint of total pain relief over the first 8 hours. For other efficacy endpoints (sum of the pain intensity difference over the first 8 hours, subjects global evaluation, peak pain relief, peak pain intensity difference, and time to remedication) both doses of rofecoxib were better than placebo (P < or = .006) and were not distinguishable from naproxen sodium for all efficacy endpoints. All treatments were well tolerated. CONCLUSION Rofecoxib effectively treated primary dysmenorrhea, and cyclooxygenase-2-derived prostanoids play a role in the pathophysiology of primary dysmenorrhea.

Clinical dose ranging studies with finasteride, a type 2 5α-reductase inhibitor, in men with male pattern hair loss

BACKGROUND Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5alpha-reductase inhibitor, decreases the formation of dihydrotestosterone from testosterone. OBJECTIVE Two separate clinical studies were conducted to establish the optimal dose of finasteride in men with this condition. METHODS Men from 18 to 36 years of age with moderate vertex male pattern hair loss received finasteride 5, 1, 0.2, or 0.01 mg/day or placebo based on random assignment. Efficacy was determined by scalp hair counts, patient self-assessment, investigator assessment, and assessment of clinical photographs. Safety was assessed by clinical and laboratory measurements and by analysis of adverse experiences. RESULTS Efficacy was demonstrated for all end points for finasteride at doses of 0.2 mg/day or higher, with 1 and 5 mg demonstrating similar efficacy that was superior to lower doses. Efficacy of the 0.01 mg dose was similar to placebo. No significant safety issues were identified in the trials. CONCLUSION Finasteride 1 mg/day is the optimal dose for the treatment of men with male pattern hair loss and was subsequently identified for further clinical development.

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), patients 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 patients 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.

A randomized, double-blind, parallel-group study comparing the analgesic effect of etoricoxib to placebo, naproxen sodium, and acetaminophen with codeine using the dental impaction pain model.

Objective:To compare the overall analgesic effect, including time to onset, peak and duration of effect for etoricoxib 120 mg, a new COX-2 selective inhibitor, in patients with acute pain to that of placebo. Naproxen sodium 550 mg and acetaminophen/codeine 600/60 mg were the active comparators. Methods:A total of 201 patients with moderate to severe pain following surgical extraction of ≥2 third molars, of which at least the mandibular tooth was impacted, were randomly allocated to receive single oral doses of placebo (n = 50), etoricoxib 120 mg (n = 50), naproxen sodium 550 mg (n = 51), or acetaminophen/codeine 600/60 mg (n = 50). The endpoints included total pain relief over 8 hours (TOPAR8, primary end point), sum of pain intensity difference over 8 hours, patient’s global evaluation, onset, peak, and duration of analgesia. Results:Etoricoxib 120 mg had a significantly greater least squares (LS) mean TOPAR8 score than placebo (20.9 vs 5.4; P < 0.001) and acetaminophen/codeine 600/60 mg (20.9 vs 11.5; P < 0.001), and a similar LS mean TOPAR8 score to naproxen sodium 550 mg (20.9 vs 21.3). All three active treatments had rapid onset of analgesia, median time ~30 minutes. The duration of analgesic effect, defined as median time to rescue medication use, was >24 hours for etoricoxib, 20.8 hours for naproxen sodium, 3.6 hours for acetaminophen/codeine, and 1.6 hours for placebo. Discussion:Etoricoxib is a new COX-2 selective inhibitor under development for treatment of osteoarthritis, rheumatoid arthritis, and acute pain. In this study, etoricoxib 120 mg provided rapid and long-lasting pain relief to patients with moderate-to-severe postdental surgery pain. Etoricoxib was generally well tolerated.

Analgesic Efficacy of Etoricoxib in Primary Dysmenorrhea: Results of a Randomized, Controlled Trial

Objective: To determine the efficacy of etoricoxib in the treatment of primary dysmenorrhea. Methods: Seventy-three women were randomly assigned to receive single oral doses of etoricoxib 120 mg, placebo, or naproxen sodium 550 mg at the onset of moderate to severe pain associated with menses. During 3 consecutive menstrual cycles in this double-blind, 3-period, crossover study, pain intensity and pain relief were assessed over the 24-hour period following dosing, and global ratings of therapy were made at 8 and 24 h after dosing. Tolerability was assessed by spontaneous reports of adverse experiences. Results: Etoricoxib 120 mg provided analgesic efficacy superior to placebo for the primary endpoint, total pain relief over 8 h (TOPAR8, p < 0.001), and for all secondary endpoints (p < 0.050). The analgesic effect of etoricoxib 120 mg over the first 8 h was similar to that of naproxen sodium 550 mg. All treatments were well tolerated. Conclusions: Etoricoxib 120 mg provided rapid and sustained analgesia that was superior to placebo and similar to that of naproxen sodium 550 mg.

Dose ranging trial of the effect of MK‐966 in primary dysmenorrhea

Clinical Pharmacology & Therapeutics (1999) 65, 118–118; doi:

MK-0703 (a cyclooxygenase-2 inhibitor) in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study.

MK-0703 is a selective cyclooxygenase-2 inhibitor investigated for the treatment of acute pain and inflammation. The purpose of this single-dose, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was to compare MK-0703 12.5, 50, and 100 mg with ibuprofen 400 mg or placebo in patients who experienced moderate to severe pain after surgical removal of at least 2 third molars. Overall analgesic effect, duration of analgesic effect, time to onset of analgesic effect, peak analgesic effect, and tolerability were assessed over a 24-hour postdose period. The primary endpoint of this study was total pain relief over 8 hours postdose. The study included 121 patients (mean age, 23 yr); 16, 31, 28, 31, and 15 patients enrolled in the placebo, MK-0703 12.5 mg, MK-0703 50 mg, MK-0703 100 mg, and ibuprofen 400 mg groups, respectively. Both MK-0703 50 and 100 mg were significantly more effective than placebo for all endpoints (P < 0.01) and comparable with ibuprofen 400 mg. The onset of analgesic effect in the MK-0703 50 mg and 100 mg and ibuprofen 400 mg groups did not differ significantly from each other (P > 0.20). MK-0703 was generally well tolerated in single doses up to 100 mg. In summary, MK-0703 50 and 100 mg were efficacious in the treatment of postoperative dental pain and were indistinguishable from the active comparator, ibuprofen 400 mg.

The COX-2 specific inhibitor, MK-0966, is effective in the treatment of primary dysmenorrhea

Clinical Pharmacology & Therapeutics (1999) 65, 118–118; doi:

Efficacy and tolerability of the cyclooxygenase‐2 inhibitor L‐791,515 compared with ibuprofen in patients with postoperative dental pain

L‐791,515 (L)[(5S)‐5‐ethyl‐3‐isopropoxy‐5‐methyl‐4‐[4‐(methylsulfonyl)phenyl]furan‐2(5 H)‐one] is a selective cyclooxygenase‐2 inhibitor investigated for treatment of acute pain and inflammation.