Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials.

The novel capsid-binding antiviral pleconaril inhibits in vitro replication of most rhinoviruses and enteroviruses. Oral pleconaril treatment was studied in 2 parallel randomized, double-blind, placebo-controlled trials. Among 1363 picornavirus-infected participants (65%) in the studies combined, the median time to alleviation of illness was 1 day shorter for pleconaril recipients than for placebo recipients (P<.001). Cold symptom scores and frequency of picornavirus cultured from nasal mucus specimens were lower among pleconaril recipients by day 2 of treatment. No treatment effects were seen in those without picornavirus infection. Pleconaril was associated with a higher incidence of nausea (6% vs. 4%) and diarrhea (9% vs. 7%) and with small increases in mean serum cholesterol levels and platelet counts, compared with baseline measurements. A subsequent 6-week prophylaxis study found that pleconaril induces cytochrome P-450 3A enzymes, which metabolize a variety of drugs, including ethinyl estradiol. Early pleconaril treatment was well tolerated and significantly reduced the duration and severity of colds due to picornaviruses in adults.

Effects of valdecoxib in the treatment of chronic low back pain: results of a randomized, placebo-controlled trial.

BACKGROUND: Valdecoxib, a cyclooxygenase (COX)-2 specific inhibitor, is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and primary dysmenorrhea. Therapeutic doses of COX-2 specific inhibitors are as effective as nonspecific nonsteroidal anti-inflammatory drugs in reducing inflammatory pain while sparing the gastrointestinal and platelet toxicity associated with nonspecific COX-1 inhibition. OBJECTIVE: The aim of this study was to assess the analgesic efficacy and tolerability of valdecoxib 40 mg/d compared with placebo in the treatment of chronic low back pain. METHODS: This 4-week, prospective, randomized, double-blind placebo-controlled, parallel-group study was conducted at 37 centers across the United States and 5 centers in Canada. Patients aged > or =18 years with chronic low back pain in flare were enrolled. Patients were randomized to receive valdecoxib 40-mg/d or placebo tablets, once daily for 4 weeks. Patients rated low back pain intensity on a visual analog scale and completed the Roland-Morris Disability Questionnaire and the modified Brief Pain Inventory-Short Form (mBPI-SF) at each visit. RESULTS: Two hundred ninety-three patients were enrolled. The valdecoxib group comprised 148 patients (81 women, 67 men; mean [SD] age, 48.6 [13.3] years; mean [SD] body weight, 86.6 [20.9] kg), and the placebo group included 145 patients (85 women, 60 men; mean [SD] age, 48.7 [12.6] years; mean [SD] body weight, 85.6 [19.9] kg). Of the enrolled patients, 249 completed the study: 134 patients (91%) who received valdecoxib and 115 patients (79%) who received placebo. No statistically significant differences in patient baseline characteristics were noted between treatment groups, except in response to 1 mBPI-SF question; patients in the valdecoxib group reported significantly greater interference in relations with other people due to pain than did those in the placebo group (P = 0.048). Changes from baseline in low back pain intensity were significantly greater in valdecoxib-treated patients at each assessment (all, P < 0.001 vs placebo). Pain scores on the mBPI-SF indicated significantly greater pain relief with valdecoxib at each assessment (all, P < or = 0.014 vs placebo). Improvements in mean Roland-Morris Disability Questionnaire score with valdecoxib were significantly greater than with placebo at each assessment (all, P < or = 0.003). Although the overall incidence of adverse events (AEs) was significantly higher among patients receiving valdecoxib than those receiving placebo (35.1% vs 24.1%, respectively; P = 0.042), no significant differences were found between groups for the incidence of any individual AE. Most AEs (89% [77/87 total events]) were mild or moderate in severity. CONCLUSIONS: In this study of patients with chronic low back pain, valdecoxib 40 mg/d provided rapid relief (within 1 week) and consistent relief (over 4 weeks). In addition, significant improvement in function and decreased disability were found with valdecoxib compared with placebo.