Comparison of the systemic bioavailability of mometasone furoate after oral inhalation from a mometasone furoate/formoterol fumarate metered-dose inhaler versus a mometasone furoate dry-powder inhaler in patients with chronic obstructive pulmonary disease.

BACKGROUND: Coadministration of mometasone furoate (MF) and formoterol fumarate (F) produces additive effects for improving symptoms and lung function and reduces exacerbations in patients with asthma and chronic obstructive pulmonary disease (COPD). The present study assessed the relative systemic exposure to MF and characterized the pharmacokinetics of MF and formoterol in patients with COPD. METHODS: This was a single-center, randomized, open-label, multiple-dose, three-period, three-treatment crossover study. The following three treatments were self-administered by patients (n = 14) with moderate-to-severe COPD: MF 400 µg/F 10 µg via a metered-dose inhaler (MF/F MDI; DULERA(®)/ZENHALE(®)) without a spacer device, MF/F MDI with a spacer, or MF 400 µg via a dry-powder inhaler (DPI; ASMANEX(®) TWISTHALER(®)) twice daily for 5 days. Plasma samples for MF and formoterol assay were obtained predose and at prespecified time points after the last (morning) dose on day 5 of each period of the crossover. The geometric mean ratio (GMR) as a percent and the corresponding 90% confidence intervals (CI) were calculated for treatment comparisons. RESULTS: Systemic MF exposure was lower (GMR 77%; 90% CI 58, 102) following administration by MF/F MDI compared to MF DPI. Additionally, least squares geometric mean systemic exposures of MF and formoterol were lower (GMR 72%; 90% CI 61, 84) and (GMR 62%; 90% CI 52, 74), respectively, following administration by MF/F MDI in conjunction with a spacer compared to MF/F MDI without a spacer. MF/F MDI had a similar adverse experience profile as that seen with MF DPI. All adverse experiences were either mild or moderate in severity; no serious adverse experience was reported. CONCLUSION: Systemic MF exposures were lower following administration by MF/F MDI compared with MF DPI. Additionally, systemic MF and formoterol exposures were lower following administration by MF/F MDI with a spacer versus without a spacer. The magnitude of these differences with respect to systemic exposure was not clinically relevant.

Evaluation of the comparative efficacy of etoricoxib and ibuprofen for treatment of patients with osteoarthritis: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To directly compare the efficacy and safety of etoricoxib, 30 mg once daily, ibuprofen, 800 mg 3 times daily, and placebo for treatment of osteoarthritis (OA) of the hip and knee. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled trial of patients with OA of the knee or hip was performed between February 2003 and November 2003 in 61 medical centers in the United States. Qualified patients aged 40 to 89 years were randomized to receive placebo, etoricoxib, 30 mg once daily, or ibuprofen, 800 mg 3 times daily, for 12 weeks. Primary efficacy end points Included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales and Patient Global Assessment of Disease Status. Response to treatment was assessed by the time-weighted average change from baseline over 12 weeks. RESULTS: In 528 patients, baseline values for the 3 primary end points ranged from 67.78 to 72.60 mm (0-100 mm visual analog scale). Near-maximal efficacy was achieved by week 2 with both active treatments and sustained over the course of the trial. During the 12-week period, least squares mean changes in the primary end points (Western Ontario and McMaster Universities Osteoarthritis Index and Patient Global Assessment of Disease Status subscales) ranged from -16.53 to -13.55 mm, -27.89 to -23.68 mm, and -26.53 to -22.97 mm in the placebo, etoricoxib, and Ibuprofen groups, respectively. Both etoricoxib and ibuprofen were more effective (P<.001) than placebo for all primary end points. Etoricoxib and ibuprofen treatment responses for the primary end points were determined to be comparable with use of prespecified comparability criteria. Results for all other efficacy end points were consistent with responses observed for the primary end points. Etoricoxib and ibuprofen generally were well tolerated. CONCLUSION: For patients with OA, treatment with etoricoxib, 30 mg/d, is well tolerated and provides sustained clinical effectiveness that is superior to placebo and comparable to ibuprofen, 2400 mg/d.