Long-term safety of tiotropium/olodaterol in older patients with moderate-to-very-severe COPD in the TONADO® studies.

Older patients with chronic obstructive pulmonary disease (COPD) may be at increased risk of adverse events (AEs) due to decreased protective organ function and increased comorbidities. TONADO® 1 + 2 were replicate, randomized, double-blind, parallel-group, 52-week, Phase III trials comparing the efficacy and safety of tiotropium/olodaterol (5/5 µg) versus the monocomponents via the Respimat® inhaler in patients with moderate-to-very-severe COPD. In this prespecified safety analysis, patients were grouped by age. Of 3100 patients, 1585 (51.1%) were aged <65 years, 1198 (38.7%) 65-<75 years, 309 (10.0%) 75-<85 years, and eight (0.3%) ≥85 years. At baseline, 23.4% had a pre-existing cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diagnosed diabetes. Overall, there was no increase in major adverse cardiac events, other AEs, or serious AEs with tiotropium/olodaterol versus the monocomponents in any age group, supporting the safety of tiotropium/olodaterol in older patients with COPD.

Effect of tiotropium and olodaterol on symptoms and patient-reported outcomes in patients with COPD: results from four randomised, double-blind studies.

Chronic obstructive pulmonary disease is associated with significant morbidity and mortality. Trials of maintenance chronic obstructive pulmonary disease treatments focus on improvement in lung function and reductions in exacerbations, while patients are much more concerned about symptoms and health status. Our aim was to investigate the effects of tiotropium + olodaterol on patient-reported health outcomes, breathlessness and night-time rescue medication use in patients with chronic obstructive pulmonary disease, compared to placebo, tiotropium or olodaterol monotherapy. Two pairs of replicate, phase III studies of 12 (OTEMTO 1 + 2) and 52 weeks' (TONADO 1 + 2) duration were evaluated, in which patients received either tiotropium + olodaterol 2.5/5 or 5/5 µg, tiotropium 2.5 or 5 µg, olodaterol 5 µg or placebo, all delivered once daily via Respimat inhaler. Patient-reported outcomes included breathlessness assessed by transition dyspnoea index focal score, health status assessed by St George's Respiratory Questionnaire total score and night-time rescue medication use at 12 or 24 weeks. Outcomes from the pooled study data are reported. Overall, 1621 and 5162 patients were treated in the OTEMTO and TONADO trials, respectively. Significantly larger improvements in St George's Respiratory Questionnaire and transition dyspnoea index focal scores were observed and a greater proportion of patients were responders to therapy (based on minimum clinically important differences in St George's Respiratory Questionnaire and transition dyspnoea index) with tiotropium + olodaterol compared to either monotherapy or to placebo. Tiotropium + olodaterol 5/5 µg significantly reduced night-time rescue medication usage. CHRONIC OBSTRUCTIVE PULMONARY DISEASE: COMBINED INHALER PROVES EFFECTIVE: Results from four in-depth studies show that a combined inhaler is very effective for treatment of moderate to severe chronic lung disease. Alleviating the symptoms of chronic obstructive pulmonary disease (COPD), particularly sleep disturbance, is crucial to enhancing patients' quality of life. Gary Ferguson at the Pulmonary Research Institute of Southeast Michigan, together with other scientists across the USA and Germany, analysed data from four large-scale studies to evaluate the efficacy of STIOLTO Respimat, a combination of two bronchodilators-tiotropium, and olodaterol, which tackle airway obstruction and breathlessness, improving long-term lung function. They found that the new drug combination triggered significant improvements in patients' quality of life and levels of breathlessness. Use of night-time rescue medication in patients on STIOLTO Respimat was considerably reduced. A greater number of patients responded positively to the combined inhaler than to monotherapy.

Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO® and OTEMTO® studies: a subgroup analysis by age.

BACKGROUND: Increasing age is associated with poor prognosis in patients with COPD. OBJECTIVE: This analysis from the replicate Phase III OTEMTO® and TONADO® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting ß2-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years. METHODS: In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg or 2.5 µg (TONADO only), olodaterol 5 µg (TONADO only), or placebo (OTEMTO only). This analysis used the approved doses of tiotropium + olodaterol 5/5 µg, tiotropium 5 µg, and olodaterol 5 µg. Primary end points at 12 weeks (OTEMTO) or 24 weeks (TONADO) included St George's Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 3 hours (AUC0-3) response, and trough FEV1 response. RESULTS: A total of 1,621 patients were randomized (40 years to <65 years, n=749; 65 years to <75 years, n=674; 75 years to <85 years, n=186; ≥85 years, n=12) in OTEMTO and 5,162 patients (40 years to <65 years, n=2,654; 65 years to <75 years, n=1,967; 75 to <85 years, n=528; ≥85 years, n=13) in TONADO. FEV1 AUC0-3 and trough FEV1 responses improved with tiotropium + olodaterol 5/5 µg at 12 weeks and 24 weeks compared to monotherapies or placebo for all age groups. SGRQ scores generally improved with tiotropium + olodaterol 5/5 µg after 12 weeks in OTEMTO and improved after 24 weeks in all age groups in TONADO. In all age groups receiving tiotropium + olodaterol 5/5 µg compared to monotherapies or placebo, transition dyspnea index scores generally improved, while rescue medication usage improved. CONCLUSION: No differences were noted in relative responses to treatment or safety when using tiotropium + olodaterol 5/5 µg compared to monotherapies or placebo across all age groups.

Pooled subpopulation analyses of the effects of roflumilast on exacerbations and lung function in COPD.

BACKGROUND: This post-hoc analysis examined the impact of roflumilast on chronic obstructive pulmonary disease (COPD) exacerbations and lung function in patients with COPD who received concomitant long-acting ß2-agonists (LABA) with or without prior inhaled corticosteroid (ICS) and the influence of various demographic and clinical characteristics on these outcomes. METHODS: Data were pooled from 2 double-blind, placebo-controlled, 52-week studies of once-daily roflumilast 500 µg in patients with COPD. Endpoints were mean rate of exacerbations and change from baseline in pre- and postbronchodilator FEV1. RESULTS: In this pooled analysis (N = 3091), addition of roflumilast to LABAs for 1 year in patients who discontinued ICS prior to study entry (n = 945) significantly reduced the risk of COPD exacerbations vs. placebo by 19.2% (p < 0.05) and significantly improved pre- and postbronchodilator FEV1 by 40 mL and 34 mL, respectively (both, p < 0.01). Similar improvements were observed in patients who received concomitant LABAs but were not taking ICS prior to study entry (n = 597). A significant reduction in COPD exacerbation risk with roflumilast vs. placebo was observed regardless of age or smoking status, and in patients who had severe or very severe COPD. Significantly improved lung function was observed with roflumilast in all the subgroups (p < 0.05), with the exception of patients with moderate COPD. CONCLUSIONS: Roflumilast reduced exacerbation rates and improved lung function in patients with COPD who received concomitant LABA, regardless of prior ICS use, and across various patient subgroups regardless of age and smoking status. CLINICALTRIALSGOV REGISTRATION NUMBERS: NCT00297102 (M2-124) and NCT00297115 (M2-125).

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

BACKGROUND: To determine the safety and efficacy of BEA2180, an anticholinergic agent in patients with chronic obstructive pulmonary disease (COPD). METHODS: Smokers 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 George's Respiratory Questionnaire (SGRQ) total score, exacerbations and adverse events. RESULTS: Patients (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). CONCLUSION: All 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.

Profile of ciclesonide for the maintenance treatment of asthma.

Ciclesonide is a nonhalogenated synthetic inhaled corticosteroid (ICS) that has been approved by the US Food and Drug Administration for the treatment of all severities of persistent asthma. It is available as a hydrofluroalkane pressurized metered-dose inhaler in two strengths, 80 mcg/activation and 160 mcg/activation, with the recommenced dosage being two inhalations twice-daily. It is a prodrug that is converted in the lung to its active form, which possesses 100-fold greater glucocorticoid-receptor-binding affinity than the parent compound. Its relative receptor affinity is similar to budesonide. In clinical studies, ciclesonide was effective in improving pulmonary function, reducing asthma symptoms, and reducing or eliminating the need for oral corticosteroids (OCSs). Patients with severe asthma dependent on OCSs and high doses of ICSs were able to achieve greater asthma control and reduce or even eliminate the use of OCSs when switched to ciclesonide. In comparison with fluticasone propionate and budesonide, ciclesonide was demonstrated to be at least as effective in maintaining pulmonary function and asthma control. In clinical trials, ciclesonide was well tolerated, with the majority of adverse events considered mild or moderate in intensity. It had low systemic bioavailability and no clinically significant hypothalamic-pituitary-adrenal axis suppression at therapeutic doses. Its safety profile establishes ciclesonide as an important addition to the currently available ICSs.

Effectiveness of omalizumab in reducing corticosteroid burden in patients with moderate to severe persistent allergic asthma.

BACKGROUND: Asthma guidelines advocate maintaining asthma control while minimizing corticosteroid exposure. OBJECTIVE: To assess the reduction in corticosteroid burden during long-term treatment and the corresponding impact of this reduction on asthma control, lung function, and inflammation in patients with moderate to severe allergic asthma. METHODS: We conducted a pooled analysis (N = 1,071) of 2 similarly designed, randomized, double-blind, placebo-controlled omalizumab trials and their extension phases. Each study included a 16-week steroid-stable phase, a 12-week steroid-reduction phase, and a 24-week extension phase. Patients received subcutaneous omalizumab (minimum, 0.016 mg/kg/IU (IgE/mL) every 4 weeks) or placebo every 2 or 4 weeks. Outcomes included change from baseline in inhaled corticosteroid dose, number of oral corticosteroid bursts, and other clinical measures, including asthma exacerbations and change in asthma quality-of-life score (questionnaire), lung function, and eosinophil count. RESULTS: The median reduction from baseline in inhaled corticosteroid dose (beclomethasone dipropionate equivalent dose) by the completion of the extension phase was greater for the omalizumab group than for the placebo group (-420.0 vs -252.0 µg/d; P < .001). During that time, omalizumab-treated patients required fewer oral corticosteroid bursts overall for treatment of acute exacerbations (mean, 0.2 vs 0.3; relative risk, 0.56; 95% confidence interval, 0.41 to 0.76; P < .001) and demonstrated greater improvements in measures of asthma control. CONCLUSION: The addition of omalizumab to baseline therapy in patients 12 years or older with moderate to severe persistent allergic asthma resulted in a durable reduction in the overall steroid burden and improvement in other clinical measures of asthma control.

Differences in physicians' self-reported knowledge of, attitudes toward, and responses to the black box warning on long-acting beta-agonists.

BACKGROUND: Inhaled corticosteroids and long-acting beta-agonists (LABAs) are recommended for treating moderate to severe persistent asthma. The Food and Drug Administration has issued a black box warning (BBW) for LABAs. OBJECTIVE: To investigate physician knowledge of the BBW and its effect on the practice of specialists (pulmonologists and allergists) and primary care physicians (PCPs) (internists and family physicians). METHODS: A total of 1,107 physicians responded to a questionnaire to determine their awareness of the BBW and whether it changed their practice. RESULTS: The group comprised 429 pulmonologists (38.8%), 395 allergists (35.7%), 141 internists (12.7%), 132 family physicians (11.9%), and 10 pediatricians (0.9%). Comparing specialists with PCPs, there was approximately a 10% difference in the rate of knowledge concerning the BBW (99.0% vs 90.8%, P < .001). Approximately a quarter of specialists agreed with the BBW compared with 52.9% of family physicians and 40.3% of internists. Twice as many PCPs vs specialists agreed with the warning (45.6% vs 24.2%, P < .001). The PCPs were more likely to alter their prescribing habits than were specialists (40.1% vs 34.6%, P < .005). Specialists were more likely to discuss the warning with patients than were PCPs (87.4% vs 64.8%, P < .001). For mild persistent asthma, most respondents chose inhaled corticosteroids as the preferred first-line therapy, but 11.4% of PCPs and 2.1% of specialists identified LABA monotherapy as their first choice. For moderate to severe asthma, the pattern of response was similar. CONCLUSION: Although most physicians were aware of the BBW for LABAs, there was a difference in how specialists and PCPs approached it and altered their prescribing habits.

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 microg QD PM, MF-DPI 400 microg 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 microg QD PM and 400 microg 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 microg BID reported a statistically significant (19%) reduction in COPD symptom scores compared with placebo (P < 0.001). Health status as measured with St. George's Respiratory Questionnaire (SGRQ) improved significantly in all domains (Total, Activity, Impacts, and Symptoms) in the pooled MF-DPI groups versus placebo (P < or = 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.

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 microg QD PM (1 inhalation), MF-DPI 200 microg BID, or placebo; in study 2 (n = 400), patients received MF-DPI 200 microg QD PM, MF-DPI 400 microg QD PM (1 inhalation), MF-DPI 200 microg BID, MF-DPI 400 microg QD PM (2 inhalations of 200 microg), 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 microg QD PM. In conclusion, the results from two placebo-controlled trials suggest that MF-DPI 400 microg/d, administered once or twice-daily, produces consistent, statistically, and clinically significant improvement in HRQOL measures in patients with persistent asthma.

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

BACKGROUND: The 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. METHODS: An 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. RESULTS: A 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). CONCLUSION: IB+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).

Mometasone furoate dry powder inhaler: a once-daily inhaled corticosteroid for the treatment of persistent asthma.

BACKGROUND: Mometasone furoate (MF), a potent synthetic inhaled corticosteroid (ICS) with a high affinity for the glucocorticoid receptor, is approved for use in the treatment of asthma. SCOPE: Publications reviewed in this article were identified via searches of MEDLINE and EMBASE databases using the terms 'mometasone furoate AND pharmacology' and 'mometasone furoate AND asthma AND clinical trial'. Data from abstracts presented at respiratory society meetings, and relevant background information, are also reviewed. FINDINGS: In clinical studies, MF, administered by dry powder inhaler (MF-DPI), was effective in treating all severities of persistent asthma, improving pulmonary function, reducing asthma symptoms, and reducing or eliminating the need for oral corticosteroids. Once-daily dosing of MF-DPI was effective in patients with mild or moderate persistent asthma previously taking twice-daily regimens of inhaled corticosteroids (ICSs), and in patients taking only inhaled beta2-agonists for symptom relief. Once-daily dosing in the evening with MF-DPI 200 microg conferred a greater benefit than morning dosing with MF-DPI 200 microg. Patients with severe asthma who were dependent on oral corticosteroids (OCSs) and high doses of ICSs were able to achieve greater asthma control and reduce or even eliminate OCSs when switched to MF-DPI. In trials of up to 1 year in duration, MF-DPI was well tolerated, with the majority of adverse events considered mild or moderate in intensity. MF had low systemic bioavailability and no clinically significant hypothalamic-pituitary-adrenal-axis suppression at therapeutic doses. The DPI device is a multiple-dose inhaler with a counter containing agglomerates of MF and lactose. Patients of all severities of persistent asthma were able to generate and maintain airflow profiles necessary to provide a uniform and accurate dose. LIMITATIONS: Only one study evaluated both morning and evening administration of once-daily doses, and one of the comparative clinical trials was an open-label study. CONCLUSION: Once-daily administration of MF-DPI 200-400 microg in patients with mild to moderate persistent asthma effectively improved lung function and asthma control. In patients with severe persistent asthma dependent on oral corticosteroids, treatment with MF-DPI 400 microg BID permitted substantial reduction of oral corticosteroid use. All MF-DPI treatments were well tolerated and had minimal systemic effects.

The appropriate omalizumab patient.

Allergy is a significant component in many asthma patients. Omalizumab is a monoclonal anti-immunoglobulin E antibody for the treatment of allergic asthma. Clinical trials have shown that omalizumab treatment is associated with improved symptom control and reduced inhaled corticosteroid doses, resulting in fewer exacerbations and reduced utilization of resources. Omalizumab therapy may benefit patients who remain uncontrolled or who cannot tolerate standard therapy.

Inhaled mometasone furoate reduces oral prednisone usage and improves lung function in severe persistent asthma.

OBJECTIVE: The reduction of oral prednisone use by mometasone furoate (MF) delivered by HFA-227 metered dose inhaler (MDI) was examined in oral corticosteroid (OCS)-dependent patients with severe persistent asthma. METHODS: A 3-month, double-blind, placebo-controlled clinical trial (n=123), followed by a 9-month open-label phase (n=120). The study was conducted at 26 medical centers in the United States. Patients were randomized to treatment with MF-MDI 400 or 800 microg twice-daily (bid) doses, or placebo in the double-blind trial. All patients received MF in the open-label phase. RESULTS: At the endpoint of the double-blind trial, MF-MDI 400 and 800 microg bid reduced the daily OCS dose by 39.4% and 31.1%, respectively, while placebo increased the OCS dose by 107.2% (P<0.01). The OCS requirement was reduced by 50% or more in 63% and 60% of patients treated with MF-MDI 400 and 800 microg bid, respectively, compared with 14% of patients receiving placebo. After 12 weeks, despite prednisone reductions, pulmonary function, asthma symptoms, albuterol use, nocturnal awakenings, and physician-evaluated response to therapy also showed significant improvement with MF-MDI treatment compared with placebo. Further reductions in OCS requirements were achieved with long-term MF-MDI treatment in the open-label phase, with an overall 67% reduction in prednisone usage and 51% of patients completely eliminating prednisone usage by the 1-year time point. CONCLUSION: MF delivered by HFA-227 MDI significantly reduces daily OCS use compared with placebo and facilitates elimination of OCS use in patients with severe persistent asthma.

Ciclesonide reduces the need for oral steroid use in adult patients with severe, persistent asthma.

STUDY OBJECTIVES: Oral corticosteroids (OCS) may be associated with systemic adverse events (AEs), which can be reduced by replacing OCS with inhaled corticosteroids (ICS). The potential of ciclesonide, a novel ICS, to reduce OCS use in patients with severe, persistent asthma was evaluated in this study. DESIGN: A phase III, 12-week, international, multicenter, double-blind, placebo-controlled, parallel-group study. PATIENTS: Adult and adolescent patients (> or = 12 years old; n = 141) with severe, persistent, oral steroid (prednisone)-dependent asthma. INTERVENTIONS: Patients were randomized to receive ciclesonide (640 mug/d or 1,280 microg/d [ex-actuator]) bid or placebo for 12 weeks. Weekly evaluations determined eligibility for prednisone dose reduction based on predetermined criteria. MEASUREMENTS AND RESULTS: The prednisone dose was significantly reduced by 47% and 63% in the groups receiving ciclesonide, 640 microg/d, and ciclesonide, 1,280 microg/d, respectively, vs an increase of 4% in the placebo group (both p < or = 0.0003) at week 12. By week 12, prednisone was discontinued by approximately 30% of patients in the ciclesonide-treated groups, vs 11% of patients in the placebo group (both p < or = 0.04). FEV1 improved significantly at week 12 in the ciclesonide treatment groups vs placebo (p < 0.03). The occurrence of local and systemic AEs was comparable between all treatment groups. CONCLUSION: Study results suggest that ciclesonide significantly reduces the need for OCS in patients with severe, persistent asthma, while maintaining asthma control.

Effects of mometasone furoate given once daily in the evening on lung function and symptom control in persistent asthma.

BACKGROUND: The chronobiology of asthma suggests that, for once-daily dosing, an evening dose may be the most effective treatment paradigm. OBJECTIVE: To evaluate the efficacy and safety of mometasone furoate dry powder inhaler (MF-DPI) administered once daily in the evening or twice daily in patients with asthma previously maintained on twice-daily regimens of inhaled corticosteroids. METHODS: In this 12-week, multicenter, placebo-controlled trial, 268 subjects > or =12 years of age with inhaled corticosteroid-dependent asthma and baseline forced expiratory volume in 1 second (FEV(1)) between 50% and 85% of predicted were randomized to receive treatment with MF-DPI 400 mug once daily in the evening, MF-DPI 200 mug twice daily, or placebo. The primary efficacy variable was mean change in FEV(1) from baseline to endpoint. Other lung function measures, asthma symptoms, quality of life, and rescue medication use also were assessed. RESULTS: At endpoint, mean FEV(1) was significantly improved with both MF-DPI doses compared with placebo (p < 0.001). The 2 active treatment groups were statistically indistinguishable from each other. Secondary efficacy variables, including nocturnal awakenings, asthma worsenings, quality of life, and rescue medication use, were also significantly improved for both MF-DPI treatments compared with placebo. Both dosages were well tolerated; no clinically meaningful changes in laboratory values or vital signs were observed. CONCLUSIONS: MF-DPI 400 mug once daily in the evening was as effective as MF-DPI 200 mug twice daily in improving pulmonary function, asthma symptoms, and quality of life compared with placebo in subjects previously using twice-daily regimens of an inhaled corticosteroid.

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

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 microg qd PM (one 400 microg 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 microg qd (once a day, quaque die) PM, 400 microg qd PM as one inhalation from a 400 microg device, 400 microg qd PM as two inhalations from a 200 microg device, 200 microg 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 microg qd PM (one inhalation; 0.41 L), MF-DPI 400 microg qd PM (2 inhalations; 0.49 L), MF-DPI 200 microg qd PM (0.41 L), and MF-DPI 200 microg 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 microg 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 microg was demonstrated between once daily in the evening and twice-daily administration. The results also confirm the effectiveness of MF-DPI 200 microg qd PM, the lowest dose studied.