Barry N. Lutsky

Comparison of once daily mometasone furoate (Nasonex) and fluticasone propionate aqueous nasal sprays for the treatment of perennial rhinitis

BACKGROUND Mometasone furoate (Nasonex), in a new once-daily aqueous nasal spray formulation, has been shown to be as effective and well-tolerated as twice-daily beclomethasone dipropionate aqueous nasal spray in treating symptoms of seasonal allergic rhinitis and perennial rhinitis. OBJECTIVE To compare the effectiveness and tolerability of mometasone furoate to placebo and to fluticasone propionate aqueous nasal spray, all treatments administered once-daily, in patients with perennial rhinitis. METHODS This was a 3-month, randomized, double-blind, double dummy, parallel group study in 550 patients, aged 12 to 77 years, at 25 centers in Canada, Latin America, and Europe. Patients allergic to at least one perennial allergen, with confirmed allergy history, skin test positivity, and moderate to severe symptomatology, were eligible to receive one of the following treatments, once daily in the morning: mometasone furoate 200 micrograms, fluticasone propionate 200 micrograms, or placebo. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. RESULTS Four hundred fifty-nine patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < .01) more effective than placebo and was not statistically different from fluticasone propionate (percent reductions from baseline were 37, 39, and 22 for mometasone furoate, fluticasone propionate, and placebo, respectively). Generally, similar trends were seen for physician-evaluated total nasal symptoms, and patient-rated and physician-rated overall condition and response to therapy. Overall, mometasone furoate was at least as effective as fluticasone propionate at equivalent doses. There was no evidence of tachyphylaxis. All treatments were well tolerated. CONCLUSION Mometasone furoate and fluticasone propionate adequately controlled symptoms of perennial rhinitis and were well tolerated.

Once-daily mometasone furoate aqueous nasal spray (Nasonex®) in seasonal allergic rhinitis: an active- and placebo-controlled study

Mometasone furoate aqueous nasal spray (Nasonex®) was compared with beclomethasone dipropionate (BDP) aqueous nasal spray in a double‐blind, randomized, placebo‐controlled, double‐dummy, parallel‐group study of adults with moderate to severe seasonal allergic rhinitis. Patients allergic to at least one tree and/or grass aeroallergen received one of the following regimens for up to 4 weeks: mometasone furoate 100 pg once daily [OD] (n = 126) or 200 μg OD (n= 126), BDP 200 μg twice daily (n = 126), or only placebo spray (n= 123). Physician‐rated nasal and total symptom scores. and global evaluation of overall condition and therapeutic response by physicians and patients, showed that the three active treatments were equally effective, and all three were significantly superior to placebo at most time points. Overall, mometasone furoate 200 μg OD demonstrated somewhat greater numerical, but not statistical, superiority to mometasone furoate 100 μg OD at the earliest evaluation time poinl. At the end of treatment, complete or marked relief was obtained in 77% of patients with mometasone furoate 100 pg/day, 79% with mometasone furoate 200 pg/day, and 74% with BDP, compared with 54% of placebo vehicle control patients. Mometasone furoate and BDP were equally well tolerated. It was concluded that mometasone furoate adequately controls symptoms of moderate to severe seasonal allergic rhinitis, offers the advantage of OD treatment, and is well tolerated.

Comparison of once-daily to twice-daily treatment with mometasone furoate dry powder inhaler

BACKGROUND Once-daily dosing with an effective inhaled corticosteroid (ICS) would likely enhance compliance and, therefore, aid in the management of asthma. OBJECTIVE Several once-daily dosing regimens of mometasone furoate (MF) administered by dry powder inhaler (DPI) were compared with a twice-daily dosing regimen in 286 patients with mild to moderate persistent asthma who were previously being treated with ICS. METHODS During a 2-week open-label phase, patients received MF-DPI, 200 microg twice daily. They were then randomized to continue MF-DPI, 200 microg twice-daily treatment or to receive MF-DPI, 200 microg once daily in the morning (AM), 200 microg once daily in the evening (PM), 400 microg once daily AM, or placebo as part of the 12-week, double-blind phase. The primary efficacy variable was the mean change from the baseline to endpoint (last evaluable observation) for FEV1. RESULTS Once-daily MF-DPI, 400 microg, AM maintained FEV1, and morning peak expiratory flow rate, FVC, FEF25%-75%, and asthma symptom scores, at levels similar to those for MF-DPI, 200 microg twice daily and significantly better than placebo. Once-daily MF-DPI, 200 microg, PM was effective in maintaining pulmonary function, but was less effective on other efficacy measures. In comparison to the other MF-DPI groups, once-daily MF-DPI, 200 microg, AM was not as effective overall. The incidence of local adverse events, including oral candidiasis, was low with all dosages. CONCLUSIONS Once-daily MF-DPI, 400 microg, AM was as effective as MF-DPI, 200 microg twice daily, whereas once-daily MF-DPI, 200 microg, was more effective when administered in the evening compared with morning, for patients receiving ICS therapy. Once-daily dosing offers an effective and convenient treatment that could aid compliance in the treatment of asthma.

Once daily mometasone furoate aqueous nasal spray is as effective as twice daily beclomethasone dipropionate for treating perennial allergic rhinitis patients

BACKGROUND Perennial allergic rhinitis is chronic and persistent, may lead to a constellation of secondary complaints including sinusitis, mouth-breathing, and some symptoms resembling a permanent cold, and often requires constant medical intervention. Well-tolerated nasal corticosteroids, alone or in combination with antihistamines, have been found to be very effective in treating this condition. OBJECTIVE To compare the effectiveness and tolerability of mometasone furoate aqueous suspension, a new once daily nasal spray, to placebo vehicle and to beclomethasone dipropionate, administered twice daily, in patients with perennial allergic rhinitis. METHODS This was a randomized, double-blind, placebo-controlled, double-dummy, parallel group study, in 427 patients age 12 years and older at 24 centers in Canada and Europe. Patients allergic to at least one perennial allergen, confirmed by medical history, skin testing, and adequate symptomatology were eligible to receive one of the following regimens for 3 months: mometasone furoate, 200 micrograms only daily; beclomethasone dipropionate, 200 micrograms twice daily (400 micrograms total dose); or placebo vehicle control. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. RESULTS Three hundred eighty-seven patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < or = .01) more effective than placebo and was indistinguishable from beclomethasone dipropionate. Similar trends were seen among individual symptoms, physician symptom evaluations, and therapeutic response. There was no evidence of tachyphylaxis. All treatments were well tolerated. CONCLUSIONS Mometasone furoate nasal spray adequately controls symptoms of perennial allergic rhinitis, offers the advantage of once daily treatment, and is well tolerated.

Dose-ranging study of mometasone furoate dry powder inhaler in the treatment of moderate persistent asthma using fluticasone propionate as an active comparator.

BACKGROUND Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a glucocorticoid with high local potency and low potential systemic availability. OBJECTIVES To compare the relative efficacy and safety of a new formulation of MF, coupled with a recently designed dry powder inhaler (DPI), in the treatment of patients with moderate persistent asthma. Fluticasone propionate administered by Diskhaler (FP Diskhaler, 250 microg twice a day; Glaxo Wellcome, Research Triangle Park, NC) was used as an active control. DESIGN A randomized, parallel group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP) trial. SETTING Sixty centers in 20 countries. PATIENTS Seven hundred thirty-three patients with moderate persistent asthma on inhaled corticosteroid treatment. INTERVENTIONS Discontinuation of previous inhaled corticosteroid and initiation of one of four study treatments: three doses of MF-DPI (100, 200, and 400 microg twice daily) and one of FP (250 microg twice daily >12 weeks). RESULTS FEV1 (primary efficacy variable) was evaluated as the mean change from baseline to endpoint (last evaluable visit). All dosage groups showed improvement at endpoint. Only 400 microg twice daily of MF-DPI (+0.19 L) was statistically different from 100 microg twice daily of MF-DPI (+0.07 L; P = 0.02). MF-DPI (200 microg twice daily) and FP Diskhaler groups showed similar improvement (+0.16 L). Greater improvement in most secondary variables (forced expiratory flow between 25% and 75% of vital capacity, and morning and evening peak expiratory flows) also resulted from treatment with 200 or 400 microg twice daily of MF-DPI or with FP Diskhaler, compared with 100 microg twice daily of MF-DPI. Overall, a total daily 800-microg dose of MF-DPI conferred no significant additional benefit >400 microg of MF-DPI. The incidence of oral candidiasis was 1%, 7%, 10%, and 10% in the 100, 200, and 400 microg twice daily of MF-DPI and FP groups, respectively. CONCLUSIONS A total daily dose of 400 microg of MF-DPI provides clinical benefit comparable to that observed with a total daily dose of 500 microg of FP Diskhaler.

Desloratadine therapy for symptoms associated with perennial allergic rhinitis

BACKGROUND Perennial allergic rhinitis (PAR) has a substantial negative social and economic impact. Recent studies emphasize the potential seriousness of PAR and the need for improved treatment of this condition. OBJECTIVE To confirm the efficacy and safety of the H1-antihistamine desloratadine in reducing the symptoms of PAR in a randomized, double-blind, placebo-controlled trial. METHODS Patients with PAR (N = 1,179) from 67 US/international centers received desloratadine, 5 mg once daily, or identical placebo tablets. The primary efficacy measure was the change from baseline to week 4 in average morning and evening reflective total symptom scores (TSSs). Secondary end points included changes from baseline in total nasal and nonnasal symptom scores and peak nasal inspiratory flow (PNIF) rates. RESULTS Desloratadine was significantly more effective than placebo in reducing morning and evening reflective TSSs for each week and during weeks 1 through 4 (P = .001). Mean changes in TSSs during the 4-week study were -3.9 (26.6% reduction) and -3.2 (22.3% reduction) for the desloratadine and placebo groups, respectively (P = .001, desloratadine vs placebo). With desloratadine therapy, significant improvements were also seen in secondary efficacy end points compared with placebo use (total nasal and nonnasal symptom scores: P < or = .04). Improvements in mean morning PNIF were significantly greater in the desloratadine-treated group than in the placebo group (P = .03). CONCLUSIONS These results confirm and extend previous findings that desloratadine is safe and is associated with a statistically significant reduction in nasal and nonnasal symptoms in patients with PAR. Objective nasal airflow, evaluated by PNIF, was statistically significantly improved after desloratadine treatment.

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.

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 ≥12 years of age with inhaled corticosteroid–dependent asthma and baseline forced expiratory volume in 1 second (FEV1) between 50% and 85% of predicted were randomized to receive treatment with MF-DPI 400 μg once daily in the evening, MF-DPI 200 μg twice daily, or placebo. The primary efficacy variable was mean change in FEV1 from baseline to endpoint. Other lung function measures, asthma symptoms, quality of life, and rescue medication use also were assessed. RESULTS At endpoint, mean FEV1 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 μg once daily in the evening was as effective as MF-DPI 200 μg 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.

Effects of treatment with mometasone furoate dry powder inhaler in children with persistent asthma

BACKGROUND Mometasone furoate dry powder inhaler (DPI) has been shown to effectively treat asthma in children. OBJECTIVE To evaluate the efficacy and safety of 2 dosing regimens of mometasone furoate DPI in the treatment of mild-to-moderate persistent asthma in children previously using inhaled corticosteroids (ICSs). METHODS A 12-week, multicenter, double-blind, parallel-group, placebo-controlled study evaluated 2 dosing regimens of mometasone furoate DPI (100 microg every evening and 100 microg twice daily) in 296 children 4 to 11 years old with asthma previously using ICSs. The primary efficacy variable was the change in percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline to end point. Secondary efficacy variables included absolute FEV1, forced expiratory flow between 25% and 75% forced vital capacity, morning and evening peak expiratory flow, asthma symptom scores, albuterol use, nocturnal awakenings, response to therapy, and health-related quality of life. RESULTS Mean changes from baseline at end point in predicted FEV1 were 4.73 and 5.52 percentage points for mometasone furoate DPI, 100 microg every evening and 100 microg twice daily, respectively, the difference of which was not significant, and -1.77 percentage points for placebo (P < or = .002). Significant improvements in secondary efficacy variables were also observed for both mometasone furoate DPI treatments over placebo. Both mometasone furoate DPI doses were well tolerated, and no significant differences were noted among the 3 treatment groups in adverse event reporting. CONCLUSIONS Both mometasone furoate DPI doses were well tolerated and significantly improved lung function, maintained effective asthma control, and improved quality of life in children with asthma.

Adult and paediatric poor metabolisers of desloratadine: an assessment of pharmacokinetics and safety

Antihistamines are widely used to treat allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) in adults and children. Desloratadine is a once-daily oral antihistamine with a favourable sedation profile that is approved for the treatment of AR and CIU. Phenotypic polymorphism in the metabolism of desloratadine has been observed, such that some individuals have a decreased ability to form 3-hydroxydesloratadine, the major metabolite of desloratadine; such individuals are termed ‘poor metabolisers of desloratadine’. This review describes the prevalence of poor metabolisers of desloratadine, quantifies the exposure to desloratadine in poor metabolisers and demonstrates that the increased exposure in poor metabolisers is independent of age when administered at age-appropriate doses. Furthermore, this review demonstrates that the increased exposure to desloratadine in poor metabolisers is not associated with any changes in the safety and tolerability profile of desloratadine, including cardiovascular safety.