Jill P. Karpel

One-year treatment with mometasone furoate in chronic obstructive pulmonary disease

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing.In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 μg QD PM, MF-DPI 400 μg BID, or placebo. The change from baseline in postbronchodilator forced expiratory volume in 1 second (FEV1), total COPD symptom scores, and health status as well as the percentage of subjects with a COPD exacerbation were assessed. Adverse events were recorded.Mometasone furoate administered via a dry powder inhaler 800 μg QD PM and 400 μg BID significantly increased postbronchodilator FEV1 from baseline (50 mL and 53 mL, respectively, versus a 19 mL decrease for placebo; P < 0.001). The percentage of subjects exacerbating was significantly lower in the pooled MF-DPI groups than in the placebo group (P = 0.043). Subjects receiving MF-DPI 400 μg BID reported a statistically significant (19%) reduction in COPD symptom scores compared with placebo (P < 0.001). Health status as measured with St. Georges Respiratory Questionnaire (SGRQ) improved significantly in all domains (Total, Activity, Impacts, and Symptoms) in the pooled MF-DPI groups versus placebo (P ≤ 0.031). MF-DPI treatment was well tolerated.Once-daily MF-DPI improved lung function and health status in subjects with moderate-to-severe COPD and was comparable to BID MF-DPI.

Efficacy and safety of mometasone furoate administered once-daily in the evening in patients with persistent asthma dependent on inhaled corticosteroids

ABSTRACT Background: Once-daily dosing with an inhaled corticosteroid (ICS) may simplify asthma management and improve patient compliance. Since asthma is frequently worse at night, evening dosing appears to be a more obvious choice to accommodate the chronobiology of asthma than morning dosing. Objective: The primary study objective was to compare the efficacy and safety of mometasone furoate (MF) dry powder inhaler (MF-DPI) 400 µg qd PM (one 400 g inhalation) with placebo for the treatment of asthma in patients previously dependent on twice a day (bid, bis in die) ICS therapy. We also compared different regimens of MF-DPI with each other and with placebo. Methods: This 12-week, multicenter, double-blind, placebo-controlled study evaluated lung function and asthma symptoms in 400 subjects with persistent asthma randomized to MF-DPI 200 µg qd (once a day, quaque die) PM, 400 µg qd PM as one inhalation from a 400 µg device, 400 µg qd PM as two inhalations from a 200 µg device, 200 µg twice daily (bid), or placebo. Evening doses were to be taken in the late afternoon or early evening, preferably before dinner time. Results: Mean changes from baseline at endpoint in FEV1 (forced expiratory volume in 1 s) were similar for MF-DPI 400 µg qd PM (one inhalation; 0.41 L), MF-DPI 400 g qd PM (2 inhalations; 0.49 L), MF-DPI 200 µg qd PM (0.41 L), and MF-DPI 200 µg bid (0.51 L); and all were significantly improved compared with placebo (0.16 L; p < 0.001). Secondary efficacy variables, including nocturnal awakenings and use of rescue albuterol, were also significantly improved with MF-DPI treatment compared with placebo. All treatments were generally safe and well tolerated, with adverse events of mild to moderate severity. Conclusions: Once-daily evening dosing of MF-DPI at doses of 400 and 200 µg restored lung function and improved nocturnal and daytime symptom control in subjects with asthma previously dependent on bid ICS therapy. Comparable effectiveness of a total daily dose of 400 µg was demonstrated between once daily in the evening and twice-daily administration. The results also confirm the effectiveness of MF-DPI 200 µg qd PM, the lowest dose studied.

Bronchodilator efficacy of the fixed combination of ipratropium and albuterol compared to albuterol alone in moderate-to-severe persistent asthma.

BACKGROUNDnThe potential of anticholinergics to provide bronchodilatory benefits over short-acting beta(2)-agonists (SABA) alone in patients with moderate-to-severe persistent asthma has not been well defined.nnnMETHODSnAn outpatient, randomized, double-blind, single-dose, crossover study in adult asthmatics with moderate-to-severe obstruction despite treatment with inhaled corticosteroids (ICS) was conducted comparing the fixed combination of ipratropium and albuterol (IB+ALB) to albuterol alone (ALB). Serial spirometry was performed over 6h. SABA were withheld for 8h, ICS and LABA for 24h.nnnRESULTSnA total of 113 patients were randomized, 106 completed the study (males n=47; mean+/-SD age=51+/-13 years). Mean+/-SD baseline FEV(1)=1.4+/-0.5 L (49+/-12% predicted). IB+ALB resulted in significantly greater improvements over ALB in the average improvement over baseline in FEV(1) as approximated from the area under the curve from 0 to 6h after drug administration (72 ml, p<0.01) and mean peak FEV(1) response (55 ml, p<0.01) as well as higher FEV(1) responses at individual time points from 0.5 to 6h postdose (p<0.01 for all). Time to onset of response was similar between groups but time to peak and duration of response were longer with IB+ALB versus ALB (120 versus 60 min and 245 versus 106 min, respectively).nnnCONCLUSIONnIB+ALB resulted in significantly greater improvement in FEV(1) and longer duration of response compared to ALB alone in patients with moderate-to-severe persistent asthma (Trial number: 1012.50; ClinicalTrial.gov NCT00096616).

Safety and efficacy of the once-daily anticholinergic BEA2180 compared with tiotropium in patients with COPD

BACKGROUNDnTo determine the safety and efficacy of BEA2180, an anticholinergic agent in patients with chronic obstructive pulmonary disease (COPD).nnnMETHODSnSmokers or ex-smokers ≥40 years with COPD and a postbronchodilator forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≤70% participated in this multinational, randomised, double-blind, parallel study. Patients received BEA2180 (50, 100 or 200 μg), tiotropium (5 μg) or placebo once daily via Respimat Soft Mist™. The primary endpoint was trough FEV1 after 24 weeks. Secondary endpoints included Transition Dyspnoea Index (TDI) focal score, St Georges Respiratory Questionnaire (SGRQ) total score, exacerbations and adverse events.nnnRESULTSnPatients (n = 2080, 64.5% male) had a mean age of 64.2 years and a baseline FEV1 of 1.2 L. Trough FEV1 at 24 weeks with all BEA2180 doses (0.044-0.087 L) and tiotropium 5 μg (0.092 L) was significantly higher (p < 0.0001) than placebo (-0.034 L) and BEA2180 (200 μg) was noninferior to tiotropium. Mean TDI focal scores were higher with BEA2180 (1.43-1.48) or tiotropium (1.46) versus placebo (0.94; p ≤ 0.01 for all). Mean SGRQ total scores also improved with BEA2180 (40.1-40.7) or tiotropium (39.5) compared with placebo (43.0, p < 0.01 for all). COPD exacerbation rates were reduced for all active treatments, reaching statistical significance for BEA2180 (50 and 200 μg) (p < 0.05, for both).nnnCONCLUSIONnAll study doses of BEA2180 improved lung function, reduced symptoms and exacerbations, and improved health status in COPD; all treatments were well tolerated. Clinical trial identifier: NCT00528996.

Inhaled Mometasone Furoate Improves Health-Related Quality of Life in Patients with Persistent Asthma

Results from two clinical trials of mometasone furoate administered via a dry powder inhaler (MF-DPI) were reviewed to evaluate the consistency of effects of MF-DPI administered once-daily in the evening (QD PM) or twice-daily (BID) on health-related quality of life (HRQOL) in adults with persistent asthma previously treated with inhaled corticosteroids. HRQOL data were collected from two 12-week, randomized, double-blind trials: in study 1 (n = 268), patients received MF-DPI 400 μ g QD PM (1 inhalation), MF-DPI 200 μ g BID, or placebo; in study 2 (n = 400), patients received MF-DPI 200 μ g QD PM, MF-DPI 400 μ g QD PM (1 inhalation), MF-DPI 200 μ g BID, MF-DPI 400 μ g QD PM (2 inhalations of 200 μ g), or placebo. In both studies, HRQOL was assessed using the Medical Outcomes Survey 36-item Short Form (SF-36) and an asthma-specific module. MF-DPI was associated with consistent, statistically significant improvements in asthma-specific total scores, breathlessness, asthma concerns, and physical symptoms compared with placebo in both trials (p < 0.05 vs. placebo). MF-DPI improved SF-36 Physical Component Summary scores at all doses except 200 μ g QD PM. In conclusion, the results from two placebo-controlled trials suggest that MF-DPI 400 μ g/d, administered once or twice-daily, produces consistent, statistically, and clinically significant improvement in HRQOL measures in patients with persistent asthma.