Randomized, double-blind, multicenter safety and efficacy study of rifalazil compared with azithromycin for treatment of uncomplicated genital Chlamydia trachomatis infection in women.

A randomized, double-blind study comparing single-dose chlamydia therapies of oral rifalazil (25 mg) and azithromycin (1 g) was conducted in 82 women with uncomplicated genital Chlamydia trachomatis infection. The microbiologic cure rate of C. trachomatis with rifalazil (n = 33) was 84.8% at the visit on day 22 to 26 (test-of-cure visit), versus 92.1% with azithromycin (n = 38), and the number of treatment failures in each group was 5 and 3, respectively. The difference in cure rate was -7.3%, with a lower limit of the 95% confidence interval (95% CI) of -22.5, and thus, noninferiority was not established at the prespecified margin (lower limit of CI of -15%). The overall treatment-emergent adverse event (TEAE) and treatment-related TEAE rates were lower in the rifalazil group (68% and 55%) than in the azithromycin group (71% and 62%), respectively. Subjects classified as treatment failures at day 22 to 26 had a lower mean plasma concentration of rifalazil at the visit on day 8 to 12 than those classified as treatment cures, but this difference was not significant; however, the levels were similar for both groups at the visit on day 22 to 26. A single 25-mg dose of rifalazil was well tolerated and eradicated C. trachomatis in most of these women with uncomplicated genital C. trachomatis infection. (The study was registered at clinicaltrials.gov under registration no. NCT01631201).

Tramadol hydrochloride extended-release once-daily in the treatment of osteoarthritis of the knee and/or hip: a double-blind, randomized, dose-ranging trial.

This 12-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial evaluated tramadol ER (extended-release tramadol) in the management of osteoarthritis pain. Adults with knee and/or hip osteoarthritis and baseline pain intensity of ≥40 on a 100-mm visual analog scale (0 = no pain, 100 = extreme pain) received once-daily tramadol ER 100 mg (n = 201), 200 mg (n = 199), or 300 mg (n = 199), celecoxib 200 mg (n = 202; to test model sensitivity), or placebo (n = 200). Coprimary efficacy variables were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, WOMAC physical function subscale, and patient global assessment of disease activity. Tramadol ER 300 mg significantly improved patient global assessment scores compared with placebo (P ≤ 0.05), but not the other 2 coprimary efficacy variables. Tramadol ER 200 and 100 mg were not significantly different from placebo for the coprimary efficacy variables. Daily diary arthritis pain intensity scores improved significantly for tramadol ER 300 and 200 mg compared with placebo. WOMAC joint stiffness subscale, physician's global assessment, arthritis pain intensity in index and nonindex joints, and overall sleep quality scores improved significantly for tramadol ER 300 mg compared with placebo. Significant differences in efficacy between celecoxib and placebo validated the model sensitivity. Adverse events occurred more frequently with tramadol ER than placebo in the gastrointestinal (nausea, constipation, diarrhea) and central nervous (dizziness, headache) systems. In this study, tramadol ER 300 mg was effective in the management of moderate to severe painful osteoarthritis of the hip or knee. A large, increasing placebo response during the study may have contributed to the lack of statistical separation between tramadol ER 200 or 100 mg and placebo.

Low-dose estradiol spray to treat vasomotor symptoms: a randomized controlled trial.

OBJECTIVE: To investigate the safety and efficacy of a transdermal estradiol (E2) spray in women with postmenopausal vasomotor symptoms. METHOD: A randomized, double-blind, placebo-controlled, multicenter, parallel-group clinical trial was conducted. Postmenopausal women (N=454) with at least eight moderate-to-severe hot flushes per day applied daily, one, two, or three E2 (90 microliter spray contains 1.53 mg E2) or matching placebo sprays. The primary efficacy endpoints were mean change from baseline in frequency and severity of moderate-to-severe hot flushes at weeks 4 and 12. RESULTS: All three E2 groups showed a significant decrease in hot flushes at weeks 4 and 12 compared with their placebo groups (P<.010). The mean change in frequency at week 12 was eight fewer flushes per day for women in the E2 groups and between four and six fewer flushes for women in the placebo groups. Women in the three- and two-E2 spray groups demonstrated significant (P<.050) reductions in severity score at weeks 4 and 12; women in the one-spray group showed significant reductions at week 5. At week 12, the majority (74-85%) of women on E2 showed at least a 50% hot flush frequency reduction as compared with 46% in the placebo group. The systemic E2 delivery rates at week 12 were approximately 0.021 mg/d, 0.029 mg/d, and 0.040 mg/d for the one-, two-, and three-spray doses, respectively. Common adverse events were similar to those previously reported with other transdermal products. Treatment-related application site reaction rate was similar to placebo (1.3% compared with 1.8%). CONCLUSION: The three dose levels of E2 spray achieved efficacy at 0.021-0.040 mg/d delivery rates. The spray is a well-tolerated, new, convenient method of delivering low-dose E2 transdermally. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00122200. LEVEL OF EVIDENCE: I.

Extended-release tramadol (tramadol ER) in the treatment of chronic low back pain.

BACKGROUND: This study evaluated the safety and efficacy of tramadol ER 300 mg and 200 mg versus placebo once daily in the treatment of chronic low back pain, using an open-label run-in followed by, without washout, a randomized controlled study design. METHODS: Adults with scores > or = 40 on a pain intensity visual analog scale (VAS; 0 = no pain; 100 = extreme pain) received open-label tramadol ER, initiated at 100 mg once daily and titrated to 300 mg once daily during a three-week open-label run-in. Patients completing run-in were randomized to receive tramadol ER 300 mg, 200 mg, or placebo once daily for 12 weeks. RESULTS: Of 619 patients enrolled, 233 (38 percent) withdrew from the run-in, primarily because of adverse event (n = 128) or lack of efficacy (n = 41). A total of 386 patients were then randomized to receive either 300 mg (n = 128), 200 mg (n = 129), or placebo (n = 129). Following randomization, mean scores for pain intensity VAS since the previous visit, averaged over the 12-week study period, increased more in the placebo group (12.2 mm) than in the tramadol ER 300-mg (5.2 mm, p = 0.009) and 200-mg (7.8 mm, p = 0.052) groups. Secondary efficacy scores for current pain intensity VAS, patient global assessment, Roland Disability Index, and overall sleep quality improved significantly (p < or = 0.029 each) in the tramadol ER groups compared with placebo. The most common adverse events during the double-blind period were nausea, constipation, headache, dizziness, insomnia, and diarrhea. CONCLUSIONS: In patients who tolerated and obtained pain relief from tramadol ER, continuation of tramadol ER treatment for 12 weeks maintained pain relief more effectively than placebo. Adverse events were similar to those previously reported for tramadol ER.

Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain.

BACKGROUND: Tramadol ER* is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. This study evaluated long-term safety of tramadol ER and effectiveness outcomes in the management of chronic, nonmalignant pain. METHODS: Patients enrolled directly for approximately 1 year of open-label tramadol ER treatment if they had chronic, nonmalignant pain (n = 919), or 'rolled over' for 38 weeks of open-label tramadol ER treatment if they completed either of two 12-week, placebo-controlled studies of tramadol ER for low back pain (n = 72) or osteoarthritis (n = 61). Tramadol ER was titrated to a dose of 300 mg once daily (patients >or= 75 years) or 300-400 mg once daily (patients < 75 years). RESULTS: A total of 257 (24%) patients completed the study. Common adverse events, regardless of treatment relationship, were nausea, dizziness (excluding vertigo), and constipation. Mean scores for current pain intensity (from 0 = no pain to 100 = extreme pain) and least, worst, and average pain intensity over the past week improved at every post-baseline visit. At each post-baseline visit, > 50% of patients provided a global assessment rating of good, very good, or excellent. Study limitations were mandatory titration to 400 mg in some patients, concomitant analgesic therapy as a confounding variable, and lack of a placebo comparator. CONCLUSIONS: Individualized dose titration and limiting once-daily therapy with tramadol ER to the maximum recommended daily dose of 300 mg may balance tolerability and analgesic effects of tramadol ER in patients with chronic, nonmalignant pain.

Extended-release tramadol in the treatment of osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: This study evaluated the efficacy and safety of tramadol extended-release (tramadol ER) tablets once daily in subjects with osteoarthritis pain. METHODS: This 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial included 1020 adults with osteoarthritis of the knee or hip and baseline pain intensity >or= 40 on a 100-mm pain visual analog scale (0 = no pain, 100 = extreme pain). Subjects took placebo or were titrated to a target dose of tramadol ER 100, 200, 300, or 400 mg once daily. MAIN OUTCOME MEASURES: The co-primary efficacy variables were pain and physical function subscales of the WOMAC Osteoarthritis Index and subject global assessment of disease activity. RESULTS: Mean changes in WOMAC Osteoarthritis Index pain and physical function subscales were significantly different between tramadol ER and placebo, overall (p