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, doubledummy, 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 ≥ 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, rofecoxib's 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 onset 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.
Background: Opiates, acetaminophen, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2-selective inhibitors such as rofecoxib are used in the treatment of acute pain ...because of their anti-inflammatory and/or analgesic properties. Rofecoxib has demonstrated an improved gastrointestinal safety profile compared with nonselective NSAIDs.
Objective: The aim of this study was to compare the analgesic efficacy and tolerability profile of rofecoxib 50 mg with those of the centrally acting, nonsalicylate, opiate/nonopiate analgesic combination oxycodone/acetominophen
5
325
mg
in patients with pain after dental surgery.
Methods: In this randomized, double-blind, placebo- and active comparator-controlled study, patients experiencing moderate to severe postoperative pain after extraction of ≥2 third molars (including ≥1 mandibular impaction) received a single oral dose of rofecoxib 50 mg, oxycodone/acetaminophen
5
325
mg
, or placebo. End points included total pain relief over 6 hours (TOPAR6, the primary end point) and 4 hours (TOPAR4), patient's global assessment of treatment at 6 hours (GLOBAL6) and 24 hours (GLOBAL24), summed pain intensity difference over 6 hours (SPID6), onset of analgesic effect (time to perceptible/meaningful pain relief, using a 2-stopwatch method), peak pain relief (PEAKPR), peak pain intensity difference (PEAKPID), and duration of analgesic effect (time to use of rescue analgesia).
Results: Two hundred twelve patients (63% female, 37% male; 76% white, 24% other; mean SD age, 20.9 4.4 years; age range, 16–41 years) were enrolled in the study and received a single oral dose of rofecoxib 50 mg (n = 90), oxycodone/acetaminophen
5
325
mg
(n = 91), or placebo (n = 31). The analgesic effect of rofecoxib was significantly greater than that of oxycodone/acetaminophen at
P < 0.001 for TOPAR6, TOPAR4, GLOBAL6, GLOBAL24, and SPID6; at
P < 0.010 for PEAKPR and PEAKPID; and at
P < 0.001 for median time to use of rescue analgesia. Significantly fewer patients in the rofecoxib group (72.2%) took rescue analgesia within 24 hours postdose compared with the oxycodone/acetaminophen group (94.5%;
P < 0.001) and the placebo group (96.8%;
P < 0.02). Both active treatments were similar with respect to onset of analgesic effect. Both were generally well tolerated; the overall incidence of adverse experiences in the rofecoxib, oxycodone/acetaminophen, and placebo groups was 51.1%, 64.8%, and 48.4%, respectively. Rofecoxib was associated with a significantly lower incidence of nausea (18.9% vs 39.6%;
P < 0.001) and vomiting (6.7% vs 23.1%;
P < 0.001) compared with oxycodone/acetaminophen.
Conclusions: In study patients with moderate to severe pain after dental surgery, rofecoxib 50 mg had a greater analgesic effect than oxycodone/acetaminophen
5
325
mg and was associated with less nausea and vomiting.
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.
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.
Context: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly ...degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated.
Objective: The objective of the study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of sitagliptin.
Design: This was a randomized, double-blind, placebo-controlled, three-period, single-dose crossover study.
Setting: The study was conducted at six investigational sites.
Patients: The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents.
Interventions: Interventions included sitagliptin 25 mg, sitagliptin 200 mg, or placebo.
Main Outcome Measures: Measurements included plasma DPP-4 activity; post-OGTT glucose excursion; active and total incretin GIP levels; insulin, C-peptide, and glucagon concentrations; and sitagliptin pharmacokinetics.
Results: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin. Sitagliptin was generally well tolerated, with no hypoglycemic events.
Conclusions: In this study in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.
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.
Background: Finasteride, an inhibitor of type 2 5α-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in ...men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated. Objective: The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA. Methods: In this 1-year, double-blind, placebo-controlled, randomized, multicenter trial, 137 postmenopausal women (41-60 years of age) with AGA received finasteride 1 mg/day or placebo. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, assessment of global photographs by a blinded expert panel, and histologic analysis of scalp biopsy specimens. Results: After 1 year of therapy, there was no significant difference in the change in hair count between the finasteride and placebo groups. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. Similarly, patient, investigator, and photographic assessments as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning, increasing hair growth, or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. Finasteride was generally well tolerated. Conclusion: In postmenopausal women with AGA, finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning. (J Am Acad Dermatol 2000;43:768-76.)
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 ≤ .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, subject’s global evaluation, peak pain relief, peak pain intensity difference, and time to remedication) both doses of rofecoxib were better than placebo (
P ≤ .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.
In this randomized, double-blind, placebo-controlled, multicenter study we assessed the analgesic effect of etoricoxib (a new cyclooxygenase-2 inhibitor) in patients having had knee or hip ...replacement surgery. A total of 228 patients with moderate or severe pain were randomly allocated within 72 h after surgery to receive etoricoxib 120 mg, controlled-release naproxen sodium 1100 mg, or placebo (1:1:1) on day 1 followed by etoricoxib and placebo (1:2) on days 2 to 7. Patients reported pain scores, rescue (opioid-combination) medication use, and the response to study drug. On day 1, etoricoxib provided an analgesic effect superior to placebo and similar to controlled-release naproxen sodium as demonstrated by the total pain relief score over 8 h, the primary end-point; least-squares mean scores were 11.0, 11.5, and 5.6, respectively (P < 0.001 versus placebo). Similarly, a larger percentage of patients receiving etoricoxib and naproxen sodium than those receiving placebo reported good to excellent responses to study drug: 53%, 60%, and 26% respectively. On days 2-7, etoricoxib demonstrated a significant reduction of rescue medication use, 35% (P < 0.001 versus placebo). The clinical relevance of the decrease was confirmed by Patient's Global Evaluation (P < 0.05 versus placebo). Patients receiving etoricoxib also experienced significantly less "worst" and "average" pain than did those on placebo. Etoricoxib was generally well tolerated in this study; the incidence of adverse experiences was infrequent and similar across treatment groups. In summary, etoricoxib provided analgesia that was similar to controlled-release naproxen sodium on day 1 and superior to placebo with reduced supplemental opioid use over 7 days.
In a postsurgery setting (knee and hip replacements), etoricoxib 120 mg provided analgesia superior to placebo and similar to controlled-release naproxen sodium 1100 mg. Patients receiving etoricoxib suffered less pain and took less opioid rescue medication compared with patients on placebo.
Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5α-reductase inhibitor, decreases the formation of dihydrotestosterone from testosterone.
Two separate clinical studies ...were conducted to establish the optimal dose of finasteride in men with this condition.
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.
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.
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.
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