Erluo Chen

Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study.

Once‐weekly alendronate 70 mg and once‐weekly risedronate 35 mg are indicated for the treatment of postmenopausal osteoporosis. These two agents were compared in a 12‐month head‐to‐head trial. Greater gains in BMD and greater reductions in markers of bone turnover were seen with alendronate compared with risedronate with similar tolerability.

Response to therapy with once-weekly alendronate 70 mg compared to once-weekly risedronate 35 mg in the treatment of postmenopausal osteoporosis.

SUMMARY Objective: The FACT study (Fosamax Actonel Comparison Trial) was a 1-year head-to-head trial comparing the efficacy and tolerability of once weekly (OW) alendronate 70 mg and OW risedronate 35 mg for the treatment of postmenopausal osteoporosis. The present analysis was performed to determine the percentage of patients who had changes during the study in BMD and biochemical markers (BCMs) of bone turnover above or below specific cut-off points. A subgroup analysis of upper gastrointestinal (UGI) tolerability was also performed. Research design and methods: 1053 postmenopausal women with low BMD were randomized to alendronate 70 mg OW (N = 520) or risedronate 35 mg OW (N = 533). The percentage of patients who had measured BMD gains ≥ 0%, ≥ 3%, and ≥ 5% after 12 months at the hip trochanter, total hip, femoral neck, and lumbar spine (LS) was analyzed. The percentage of patients who experienced any bone loss, and those with measured losses of 3% or more at these sites after 12 months, was determined. The percentage of patients achieving reductions in urinary N-telopeptide of type I human collagen (NTX) ≥ 40%, and serum C-telopeptide of type I collagen (CTx) ≥ 60%, bone-specific alkaline phosphatase (BSAP) ≥ 30%, and N terminal propeptide of type I procollagen (P1NP) ≥ 50% at 3 months and 12 months was also determined. Tolerability, based on adverse experience reporting, was evaluated in a subgroup of patients with a history of UGI disorders at baseline. Results: A greater percentage of alendronate- than risedronate-treated patients had measured BMD gains (≥ 0%) ( p < 0.05) at all sites at 12 months. Significantly more ( p < 0.01) alendronate- than risedronate-treated patients had measured gains in BMD ≥ 3% and ≥ 5% at the hip trochanter, total hip, and LS spine. Significantly more ( p < 0.05) risedronate- than alendronate-treated patients had an apparent loss of BMD (> 0% and ≥ 3% loss) at these same sites. After 3 months, significantly ( p < 0.001) more alendronate- than risedronate-treated patients achieved predefined reductions in all BCMs. Similar tolerability was demonstrated in both treatment groups, regardless of whether or not patients had a history of UGI disorders at baseline. Conclusions: Significantly more alendronate- than risedronate-treated patients achieved predefined increases in BMD at 12 months and reductions in BCMs at 3 months. Significantly more risedronate- than alendronate-treated patients were classified as apparent ‘non-responders’ (i.e. experienced any bone loss) after 12 months of therapy. The tolerability profiles of the two medications were similar.

Comparison of rofecoxib and a multidose oxycodone/ acetaminophen regimen for the treatment of acute pain following oral surgery: a randomized controlled trial

SUMMARY Objective: To compare the efficacy of a single dose of rofecoxib 50 mg with a single dose of oxycodone/acetaminophen 10/650 mg over 6 h as well as with a multidose regimen of oxycodone/acetaminophen 10/650 mg followed by oxycodone/acetaminophen 5/325 mg over 24 h. Research design and methods: In this double-blind, randomized, two-phase study, patients with moderate to severe pain after surgical extraction of ≥ 2 third molars, including one mandibular impaction, were treated with rofecoxib 50 mg, oxycodone/acetaminophen 10/650 mg (single-dose phase) followed by 5/325 mg every 6 h as needed (multidose phase), or placebo. Patients rated their pain relief and intensity at 18 time points over 24 h. Efficacy was measured over 6 and 24 h by total pain relief (TOPAR), sum of pain intensity difference (SPID), and patient global assessment of response to therapy (PGART). Primary endpoint for the single dose comparison was TOPAR over 6 h; SPID was the key 24-h endpoint. Onset of analgesic effect, peak analgesic effect, and duration of analgesic effect were also evaluated. Adverse experiences were recorded. Results: 271 patients were randomized to treatment with rofecoxib (n = 121), oxycodone/acetaminophen (n = 120), or placebo (n = 30). For the single dose comparison, rofecoxib-treated patients achieved pain relief at least as effective as oxycodone/acetaminophen-treated patients as assessed by TOPAR6 (12.9 vs 11.3, 95% CI on difference = [–0.1, 3.2], p = 0.059). Patients also rated a single dose of rofecoxib as at least as effective as multidose oxycodone/acetaminophen over 24 h on SPID24 (21.9 vs 18.1, 95% CI on difference = [–1.0, 8.8], p = 0.122). Patients treated with oxycodone/acetaminophen had a shorter time to onset of analgesia than patients treated with rofecoxib (24 vs 35 min, p < 0.05). Patients in the active treatment groups achieved similar peak effects during the single-dose phase. Individuals treated with rofecoxib demonstrated a longer duration of analgesic effect than those treated with a single dose of oxycodone/acetaminophen. Patients on active treatment demonstrated better efficacy than patients on placebo on these prespecified endpoints ( p < 0.001 for both comparisons). Fewer rofecoxib than oxycodone/acetaminophen patients experienced adverse events (47.9 vs 75.8%, p < 0.001), including nausea (19.0 vs 42.5%, p < 0.001), vomiting (9.9 vs 24.2%, p < 0.01), and dizziness (7.4 vs 31.7%, p < 0.001). Conclusion: Patients treated with a single dose of rofecoxib 50 mg achieved an overall analgesic effect at least as effective as patients treated with a single-dose of oxycodone/acetaminophen 10/650 mg over 6 h and multidose oxycodone/acetaminophen over 24 h, with fewer adverse experiences of nausea ( p < 0.001), vomiting ( p < 0.01), and dizziness ( p < 0.001).

Upper gastrointestinal tolerability of once weekly alendronate 70 mg with concomitant non-steroidal anti-inflammatory drug use

Background : Both oral bisphosphonates and non‐steroidal anti‐inflammatory drugs have the potential to irritate the upper gastrointestinal mucosa, and are frequently used by the same patient population.

A randomized, placebo-controlled, 6-month study of once-weekly alendronate oral solution for postmenopausal osteoporosis.

OBJECTIVE This study evaluated the overall safety and tolerability of once-weekly (OW) alendronate 70 mg oral solution (OS) versus OW placebo OS. METHODS Postmenopausal, osteoporotic women were enrolled at 51 centers in the United States in a 6-month double-blind, randomized trial. Patients were randomized (1:1) to OW alendronate 70 mg OS or placebo OS. The primary end point was the proportion of patients reporting any upper gastrointestinal (UGI) adverse event (AE) at 6 months. Secondary end points included mean percentage change in urinary N-telopeptide of type I human collagen (NTx) and serum bone-specific alkaline phosphatase (BSAP) at 6 months. RESULTS Initially, 454 women were enrolled; 392 (86.3%) completed the study. The mean (SD) age was 65.2 (10) years, and the mean (SD) time since menopause was 19.1 (12) years. The proportion of patients experiencing any UGI AE was significantly higher with alendronate OS (23.7%) compared with placebo solution (15.3%), with a treatment difference of 8.3% (95% CI, 0.8%-15.8%; P = 0.024). The proportion of patients experiencing any esophageal AE was 4.0% with alendronate and 3.0% with placebo (treatment difference, 1.0% [95% CI, -2.7% to 4.8%]). In addition, 4.5% of alendronate and 8.7% of placebo patients discontinued the study due to any clinical AE, and 3.3% of alendronate and 1.8% of placebo patients discontinued due to a UGI AE (difference, 1.5% [95% CI, -1.5% to 4.4%]). Alendronate OS produced significantly greater reductions in both NTx and BSAP than placebo (differences, -47.5% and -38.7%, respectively [both, P < 0.001]). CONCLUSIONS In this 6-month study, patients receiving OW alendronate 70 mg OS had a higher rate of UGI AEs than placebo patients. However, rates of serious UGI AEs, discontinuations due to UGI AEs, and esophageal AEs were similar between groups. UGI AEs in the study were generally mild to moderate in severity and did not result in treatment discontinuation. In addition, OW alendronate 70 mg OS significantly reduced biochemical markers of bone turnover.

A double-blind, randomized study evaluating losartan potassium monotherapy or in combination with hydrochlorothiazide versus placebo in obese patients with hypertension

ABSTRACT Objectives: The objective of this study was to evaluate the effects of losartan ± hydrochlorothiazide (HCTZ) versus placebo in obese patients with systolic and diastolic hypertension. Research design and methods: Randomized patients (n = 261) were non-diabetic with systolic blood pressure (SBP) ≥ 140 and ≤ 180 mmHg and diastolic BP (DBP) ≥ 95 and ≤ 115 mmHg, body mass index > 30 kg/m2, and waist circumference > 40 (males)/> 35 (females) inches. Patients were randomized to placebo or a forced titration of losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/HCTZ 12.5 mg, and losartan 100 mg/HCTZ 25 mg. Primary efficacy measurements were change from baseline in SBP and DBP at 12 weeks. Secondary measurements were change from baseline in BPs at 8 and 16 weeks, percent responders at 12 and 16 weeks, and safety/tolerability. Post-hoc analyses were BP at 4 weeks and achievement of controlled BP (SBP < 140 and/or DBP < 90 mmHg) at 12 and 16 weeks. Results: Losartan 50 mg reduced BP from 151.6/99.2 mmHg at baseline to 140.1/89.8 mmHg at week 4 (post hoc), 139.5/89.6 mmHg with losartan 100 mg at week 8 (secondary), 134.3/85.9 mmHg with losartan 100 mg/HCTZ 12.5 mg at week 12 (primary), and 132.1/84.9 mmHg with losartan 100 mg/HCTZ50 mg at week 16 (secondary) (all p < 0.05). Rates of clinical adverse experiences were similar between treatment groups. A limitation of these analyses is the relatively rapid rate of study drug titration, which may not have allowed for the evaluation of the full treatment effect at each titration step. Conclusions: We conclude that losartan alone or in combination with HCTZ was generally well tolerated and effective in the treatment of elevated systolic and diastolic BP in obese patients with hypertension.

Response to Oral Bisphosphonates in Subgroups of Younger and Older Postmenopausal Women

BACKGROUND Although the effects of bisphosphonates in bone are known for postmenopausal women, it is not known if younger postmenopausal women have a similar response. Furthermore, it is not known if the effects of alendronate and risedronate differ in postmenopausal women in regard to age, specifically in women at or younger than the mean age of natural menopause. Our aim was to examine the effects of two oral bisphosphonates in postmenopausal women by age. METHODS This was a post-hoc analysis of postmenopausal women <55 or > or =55 years old with low bone mineral density (BMD), randomized to once weekly alendronate 70 mg or risedronate 35 mg for 1 year with 1-year extensions in U.S. and International Fosamax Actonel Comparison Trials. RESULTS In both age subgroups of postmenopausal women, alendronate produced significantly greater mean BMD increases from baseline than risedronate at hip trochanter, lumbar spine, total hip, and femoral neck. Changes in BMD were not significantly different between younger and older alendronate-treated women, although treatment differences favoring alendronate were numerically greater for younger than older postmenopausal women at all sites. Significantly greater reductions in bone turnover markers also occurred with alendronate vs. risedronate in both subgroups. Tolerability was similar between treatments. CONCLUSIONS In this post-hoc subgroup analysis of older and younger postmenopausal women receiving alendronate or risedronate, larger treatment differences in BMD gain in younger compared with older women suggest that patient age may affect the relative efficacy of these antiresorptive drugs.