Long-term efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol.

Beclomethasone dipropionate (BDP) nasal aerosol has an established efficacy and safety profile for short-term allergic rhinitis (AR) treatment. However, managing perennial AR (PAR) symptoms often requires long-term treatment. This study evaluates efficacy and safety of long-term treatment with BDP nasal aerosol in PAR patients. In this double-blind, placebo-controlled study, patients (≥12 years [n = 529]) were randomized 4:1 to once-daily treatment with BDP nasal aerosol at 320 µg or placebo. The primary efficacy end point was change from baseline in weekly averages of patient-reported 24-hour reflective total nasal symptom score (rTNSS) over 30 weeks. Safety and tolerability of BDP nasal aerosol were also assessed. Ocular safety, including changes in intraocular pressure and severity of lens opacities (nuclear opalescence, nuclear color, cortical lens opacity, and posterior subcapsular lens opacity), was measured for patients who completed 52 weeks of treatment (n = 245). Across 30 and 52 weeks, BDP nasal aerosol significantly improved rTNSS and instantaneous TNSS (iTNSS) versus placebo (least-squares mean treatment difference, rTNSS, -0.97 for 30 weeks and -1.09 for 52 weeks, p < 0.001 for both; iTNSS, -0.96 for 30 weeks and -1.10 for 52 weeks], p < 0.001 for both). BDP nasal aerosol was well tolerated. Incidence of most adverse events with BDP nasal aerosol was similar to that with placebo, except for epistaxis, which occurred more frequently with active treatment. Severity of changes from baseline in ocular lens opacities was comparable between treatments. BDP nasal aerosol at 320 µg once daily was safe and effective for long-term PAR treatment, with no evidence of clinically adverse systemic safety events. This study was a part of the clinical trial NCT00988247 registered at www.ClinicalTrials.gov.

The efficacy and tolerability of inhaled montelukast plus inhaled mometasone compared with mometasone alone in patients with chronic asthma.

BACKGROUND: The efficacy of oral montelukast in chronic asthma is well established. Montelukast is also an effective adjunctive therapy to inhaled corticosteroids (ICS) in asthma uncontrolled on ICS alone. Inhaled montelukast was recently shown to provide significant bronchodilation compared with placebo in patients with chronic asthma. The purpose of this study was to evaluate the efficacy of inhaled montelukast added to inhaled mometasone. METHODS: This was an 8-week, multicenter, randomized, double-blind, placebo-controlled study comparing once-daily inhaled montelukast 1 mg plus inhaled mometasone 220 µg (delivered by separate dry powder inhalers) with placebo plus inhaled mometasone 220 µg. Men and women aged 15-85 years with chronic asthma, forced expiratory volume in 1 second (FEV(1)) 50-80% of the predicted value, and ß-agonist reversibility ≥12% were eligible. Patients were required to meet a minimum symptom threshold while receiving open-label inhaled mometasone during a 3-week prestudy/run-in period. Patients received blinded (montelukast vs. placebo) treatment for 2 weeks, entered a 1-week washout period, then crossed over to the other treatment for 2 weeks. The primary endpoint was the average change from baseline in FEV(1) over the 2-week treatment period. Secondary endpoints included daytime and nighttime symptom scores. Other endpoints included short-acting ß-agonist (SABA) use, asthma exacerbations, asthma control, peak expiratory flow (PEF), and blood eosinophil count. RESULTS: A total of 134 patients were randomized. For the primary endpoint, change from baseline in FEV(1), inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone (least squares mean 0.22 L vs. 0.17 L; p = .033 [two-sided at α = 0.05]). Inhaled montelukast plus inhaled mometasone was also significantly more effective than placebo plus inhaled mometasone in improving daytime asthma symptom scores (p = .005) and nighttime asthma symptom scores (p = .015), increasing the percentage of days with asthma control (p = .004), decreasing the percentage of days with asthma exacerbations (p ≤ .001), and decreasing the blood eosinophil count (p = .013). Differences were not significant on AM or PM PEF or SABA use, although the latter approached significance (p = .073). Both treatments were well tolerated. CONCLUSION: Inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone in improving FEV(1), symptoms, asthma control, and blood eosinophil count.

Effects of olopatadine hydrochloride nasal spray 0.6% in the treatment of seasonal allergic rhinitis: a phase III, multicenter, randomized, double-blind, active- and placebo-controlled study in adolescents and adults.

BACKGROUND: Seasonal allergic rhinitis (SAR) is an allergen-induced inflammatory reaction that occurs during periods of high pollen count. Current treatments for SAR include allergen avoidance, systemic antihistamines, and steroidal and nonsteroidal intranasal sprays. Olopatadine is a selective antihistamine and an inhibitor of proinflammatory mediators from human mast cells. An intranasal formulation of olopatadine has been developed for the treatment of SAR. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of olopatadine hydrochloride nasal spray 0.6% (OLO) relative to azelastine hydrochloride nasal spray 0.1% (AZE) and an inactive vehicle in the treatment of SAR. METHODS: This Phase III, multicenter, randomized, double-blind, active- and placebo-controlled, parallel-group study was conducted at 21 centers across the United States. Eligible patients were aged > or =12 years and had a history of SAR and verified allergy to a prevalent local allergen. After a run-in period during which inactive vehicle was administered, patients were randomly assigned to OLO, AZE (active control), or inactive vehicle (identical to OLO; placebo control), 2 sprays in each nostril BID for 16 days. The timing of enrollment was correlated with the start of the allergy season at each site. Symptoms were recorded twice daily in an electronic diary. Efficacy assessments included changes in mean daily reflective total nasal symptom scores (TNSS). Tolerability was evaluated based on adverse events (AEs) and nasal, physical, and cardiovascular parameters. RESULTS: A total of 544 patients were randomized. The mean age was 36 years (range, 12-77 years); men and boys represented 32.2% of the population; and the patients were predominantly white (75.4%). The mean reductions from baseline in reflective TNSS were 26.8%, 29.9%, and 18.4% with OLO, AZE, and inactive vehicle, respectively (P = 0.003 OLO vs inactive vehicle; 95% CI, -2.5% to 8.7% OLO vs AZE [non-inferiority]). The most commonly reported treatment-related AE in the OLO and AZE groups was bitter taste (12.2% [22/180] and 19.7% [37/188], respectively). The prevalence and intensity of bitter taste were significantly lower with OLO than with AZE (P = 0.05 and P = 0.005, respectively). In the group that received inactive vehicle, the prevalence of bitter taste was 1.7% (3/176). The prevalences of other treatment-related AEs, including epistaxis and nasal discomfort, were < or =3.7% in each group and did not differ significantly between groups. CONCLUSIONS: In this small study in patients aged > or =12 years with SAR, the percentage reduction from baseline in TNSS was significantly greater with OLO (2 sprays in each nostril BID) compared with vehicle and not significantly different from that with AZE. OLO and AZE were similarly well tolerated, with the exception of prevalence and intensity of bitter taste, which were significantly lower with OLO.

Comparison of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler and fixed-dose fluticasone propionate/salmeterol dry powder inhaler in asthma patients.

BACKGROUND: The adjustable-dose budesonide/formoterol dry powder inhaler (DPI) has demonstrated similar or greater asthma control with less inhaled corticosteroid compared with the fixed-dose budesonide/formoterol DPI. OBJECTIVE: We sought to evaluate the efficacy, tolerability, and resource use of maintenance therapy with the adjustable-dose budesonide/formoterol pressurized metered-dose inhaler versus the fixed-dose budesonide/formoterol pressurized metered-dose inhaler and the fixed-dose fluticasone propionate/salmeterol DPI. METHODS: This was a randomized, open-label, multicenter study of patients (N = 1225) 12 years and older with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose budesonide/formoterol (160/4.5 microg x 2 inhalations [320/9 microg] twice daily) or fixed-dose fluticasone propionate/salmeterol (250/50 microg x 1 inhalation twice daily) for 1 month (treatment period 1), after which, the fixed-dose fluticasone propionate/salmeterol group continued therapy and the fixed-dose budesonide/formoterol group was randomized 1:1 to fixed-dose budesonide/formoterol or adjustable-dose budesonide/formoterol (adjustable from 2 inhalations [320/9 microg] twice daily to 2 inhalations [320/9 microg] once daily or 4 inhalations [640/18 microg] twice daily) for 6 months (treatment period 2). RESULTS: There were no significant between-group differences in asthma exacerbations (primary variable), asthma symptoms, or lung function during the 7-month treatment period. Less study drug (inhalations per day, P < .001) was used with adjustable-dose versus fixed-dose budesonide/formoterol. All treatments were well tolerated. CONCLUSIONS: Adjustable-dose and fixed-dose budesonide/formoterol showed no differences in asthma control or tolerability versus fixed-dose fluticasone propionate/salmeterol.

Validation of the nighttime symptoms score as a clinically relevant measure of allergic rhinitis.

The aim of this study was to validate the nighttime symptoms score (NSS), which incorporates individual scores for difficulty going to sleep and nighttime awakening caused by nasal symptoms and nasal congestion on awakening, as a clinically relevant measure of allergic rhinitis (AR). Fifty-five general season AR (SAR) symptom items were generated by interviews with 14 patients with symptomatic SAR without concomitant asthma for use in an Importance Rating Questionnaire (IRQ). A second group of patients (n = 83) with symptomatic AR without asthma rated the importance of each item on the IRQ. Correlation coefficients were calculated to examine the relationships between the six sleep quality questions on the IRQ and the other AR symptoms and between the symptom questions of the NSS, the Daytime Nasal Symptoms Score (DNSS), and the individual domains of the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). The majority (94%) of patients with active AR reported some degree of symptoms relating to sleep quality. The six sleep quality items on the IRQ were selected by 71-84% of patients. The sleep quality items were more highly correlated with each other (r = 0.48-0.85) than with the four items of the DNSS (r = 0.01-0.42). There was a moderate-to-strong correlation of the RQLQ sleep domain with the two sleep questions of the NSS (r = 0.44-0.57). The individual symptom questions of the NSS and the DNSS were only moderately correlated with each other. Sleep quality questions measure aspects of SAR that are not captured by daytime SAR symptoms. The results show that the NSS is a valid and relevant clinical measure of the impact of nighttime sleep disturbance on AR patients.

Two multicenter, randomized, single-blind, single-dose, crossover studies of specific sensory attributes of budesonide aqueous nasal spray and fluticasone propionate nasal spray.

BACKGROUND: Intranasal corticosteroids are effective for the treatment of allergic rhinitis. Sensory attributes associated with these sprays may affect patient preference and adherence to treatment regimens. OBJECTIVES: These 2 studies compared patients' perceptions of and preferences for specific sensory attributes of budesonide aqueous nasal spray (BANS) and fluticasone propionate nasal spray (FPNS). METHODS: In 2 multicenter, randomized, single-blind (patient), single-dose, 2-period, 1-day crossover studies, adults with mild to moderate allergic rhinitis received single doses of BANS (one 32-pg spray per nostril in both studies, 64-microg total dose) and FPNS (two 50-microg sprays per nostril in study 1, 200-pg total dose; one 50-microg spray per nostril in study 2, 100-microg total dose). Study 1 compared the once-daily recommended starting doses of BANS and FPNS, and study 2 compared BANS with half the once-daily recommended dose of FPNS to balance the number of actuations for delivery of study drug. Patients completed the 23-item Sensory Perceptions Questionnaire and indicated their product preference (if any). RESULTS: A total of 110 women and 71 men in study 1 and 136 women and 54 men in study 2 were randomized to treatment. None had previously used BANS or FPNS. In both studies, fewer patients perceived scent or taste (both P < 0.001 in both studies), forceful spray (P < 0.001 in both studies), and a wet feel in both the nose and throat (study 1, P < 0.004; study 2, P < 0.002) with BANS than with FPNS. In addition, more patients in both studies liked the spray force (study 1, P < 0.01; study 2, P < 0.001) and moisture content in the throat (study 1, P < 0.001; study 2, P < 0.006) of BANS and indicated a greater overall satisfaction with the sensory features of BANS than those of FPNS (study 1, P < 0.001; study 2, P < 0.015). In analyses that included all responding patients, 54.4% of patients in study 1 preferred BANS and 37.8% preferred FPNS (P < 0.022). In study 2, 47.4% preferred BANS and 41.1% preferred FPNS (not significant). Of the 92.2% of patients in study 1 and 88.4% in study 2 who specified a product preference, 59.0% preferred BANS and 41.0% preferred FPNS in study 1 (P = 0.021), and 53.6% preferred BANS and 46.4% preferred FPNS in study 2 (not significant). CONCLUSIONS: On the basis of perceptions of specific sensory attributes reported after 1 administration in these 2 studies, BANS was rated as more pleasing and preferred over the recommended QD starting dose of FPNS, and was also rated as more pleasing than half the QD recommended starting dose of FPNS.