Evaluation of the ocular safety associated with the exhalation delivery system with fluticasone.

Background: Intranasal corticosteroids (INCS) are the cornerstone of treatment for chronic rhinosinusitis. Although INCS are generally considered safe and effective, there is a concern that chronic use may lead to ocular adverse effects. Objective: To assess ocular safety of the exhalation delivery system with fluticasone propionate (EDS-FLU) in patients with chronic rhinosinusitis with nasal polyps. Methods: Ocular safety data were collected during two randomized, double-blind, placebo controlled studies with open-label extensions. Ophthalmologists performed tonometry, slit-lamp, and visual acuity examinations to assess intraocular pressure (IOP) and the presence of cataracts. Ocular examinations were conducted before double-blind treatment, at the end of the 16-week double-blind phase, and at the end of the 8-week open-label phase. The results of pooled data from patients who received EDS-FLU 186 µg (n = 160), EDS-FLU 372 µg (n = 161), and EDS-placebo (n = 161) twice daily are reported here. Results: At the end of the double-blind phase, six patients developed elevated average IOP > 21 mm Hg: two patients (1.2%) in the EDS-placebo group, three patients (1.9%) in the EDS-FLU 186 µg group, and one patient (0.6%) in the EDS-FLU 372 µg group. In addition, 6 of 482 patients developed cataracts: 3 patients in the EDS-placebo group, 2 patients in the EDS-FLU 186 µg group, and 1 patient in the EDS-FLU 372 µg group. At the end of the open-label phase, two additional patients showed IOP > 21 mm Hg and two additional patients developed cataracts. Conclusion: No increased risk of elevated IOP was detected with EDS-FLU; the rate of cataract development was similar to EDS-placebo and to that reported with other INCS.Clinical trials NCT01622569 and NCT01624662, www.clinicaltrials.gov.

The interleukin-4/interleukin-13 pathway in type 2 inflammation in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells. The activation of these immune cells results in a range of pathologic effects including immunoglobulin E production, an increase in the number of smooth muscle cells within the nasal mucosa and a reduction in their contractility, increased deposition of fibrinogen, mucus hyperproduction, and local edema. The cytokine-driven structural changes include nasal polyp formation and nasal epithelial tissue remodeling, which perpetuate barrier dysfunction. Type 2 inflammation may also alter the availability or function of olfactory sensory neurons contributing to loss of sense of smell. Targeting these key cytokine pathways has emerged as an effective approach for the treatment of type 2 inflammatory airway diseases, and a number of biologic agents are now available or in development for CRSwNP. In this review, we provide an overview of the inflammatory pathways involved in CRSwNP and describe how targeting key drivers of type 2 inflammation is an effective therapeutic option for patients.

Dupilumab improves outcomes in patients with chronic rhinosinusitis with nasal polyps irrespective of gender: results from the SINUS-52 trial.

Objectives: This post hoc analysis assessed disease characteristics and response to dupilumab treatment in male and female patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (SINUS-52 study; NCT02898454). Methods: Patients received dupilumab 300 mg or placebo every 2 weeks for 52 weeks on background intranasal corticosteroids. Efficacy was assessed through Week 52 using nasal polyp score (NPS), nasal congestion/obstruction score, loss of smell score and University of Pennsylvania Smell Identification Test score. Disease-specific health-related quality of life (HRQoL) was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22). Results: The analysis included 192 male and 111 female patients. Female patients had higher mean SNOT-22 total score (56.6 vs. 49.1, P < 0.01) and more coexisting asthma (78.4% vs. 46.4%, P < 0.0001) and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) (38.7% vs. 18.8%, P = 0.0001) than male patients, but other baseline characteristics were similar. Dupilumab significantly improved CRSwNP outcomes vs. placebo at Week 52, regardless of gender: least squares mean differences (95% confidence interval) for NPS were -2.33 (-2.80, -1.86) in male and -2.54 (-3.18, -1.90) in female patients (both P < 0.0001 vs. placebo), and for SNOT-22 were -19.2 (-24.1, -14.2) in male and -24.4 (-31.5, -17.3) in female patients (both P < 0.0001 vs. placebo). There were no significant efficacy-by-gender interactions. Conclusion: Female patients had greater asthma, NSAID-ERD and HRQoL burden at baseline than male patients. Dupilumab treatment significantly improved objective and subjective outcomes compared with placebo, irrespective of gender.

Type 2 Inflammation and Asthma in Children: A Narrative Review.

Increased understanding of the underlying pathophysiology has highlighted the heterogeneity of asthma and identified that most children with asthma have type 2 inflammation with elevated biomarkers, such as blood eosinophils and/or fractional exhaled nitric oxide. Although in the past most of these children may have been categorized as having allergic asthma, identifying the type 2 inflammatory phenotype provides a mechanism to explain both allergic and non-allergic triggers in pediatric patients with asthma. Most children achieve control with low-to-medium doses of inhaled corticosteroids, however, in a small but significant proportion of children, asthma remains uncontrolled despite maximum conventional treatment, with an increased risk of severe exacerbations. In this review, we focus on the role of type 2 inflammation and allergic processes in children with asthma, together with evidence of the efficacy of available treatment options for those who experience severe symptoms.

Dupilumab 200 mg was efficacious in children (6-11 years) with moderate-to-severe asthma for up to 2 years: EXCURSION open-label extension study.

BACKGROUND: The phase 3 VOYAGE (NCT02948959) and open-label extension EXCURSION (NCT03560466) studies evaluated dupilumab in children (6-11 years) with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed the efficacy and safety of add-on dupilumab 200 mg every 2 weeks (q2w), the largest dose cohort in both studies, in children from VOYAGE who participated in EXCURSION. METHODS: Annualized rate of severe asthma exacerbations (AERs), change in prebronchodilator percent predicted forced expiratory volume in 1 s (ppFEV1), and treatment-emergent adverse events were assessed in children with moderate-to-severe asthma who received dupilumab 200 mg q2w in VOYAGE and EXCURSION (dupilumab/dupilumab arm) and those who received placebo in VOYAGE and dupilumab 200 mg q2w in EXCURSION (placebo/dupilumab arm). These endpoints were also assessed in children with moderate-to-severe type 2 asthma (defined as blood eosinophil count ≥150 cells/µL or FeNO ≥20 ppb at the parent study baseline [PSBL]). RESULTS: In the overall population, dupilumab reduced AER and improved prebronchodilator ppFEV1 in the dupilumab/dupilumab arm (n = 158) for up to 2 years. Children receiving placebo/dupilumab (n = 85) showed similar reductions after initiation of dupilumab 200 mg q2w in EXCURSION. Similar results were observed for children with type 2 asthma at PSBL. The safety profile was consistent with the known safety profile of dupilumab. CONCLUSION: In children (6-11 years) with uncontrolled moderate-to-severe type 2 asthma, dupilumab 200 mg reduced exacerbation rates and improved lung function for up to 2 years and showed safety consistent with the known dupilumab safety profile.

Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2).

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays. OBJECTIVE: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps). METHODS: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24. RESULTS: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids. CONCLUSIONS: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status.

The Effect of EDS-FLU on Objective and Patient-Reported Subjective Outcomes for Patients with Chronic Rhinosinusitis with Nasal Polyps.

BACKGROUND: Exhalation delivery system with fluticasone (EDS-FLU) delivers medication high and deep in the nasal passages and has been shown to reduce nasal polyp (NP) grade, an objective measure of efficacy, and to yield clinically meaningful improvements on subjective measures of symptoms in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVES: To better characterize EDS-FLU treatment, we analyzed responder rates for four outcome measures used in the EDS-FLU pivotal trials, in the overall study population as well as in subgroups of patients with or without prior sinus surgery or prior use of a standard intranasal corticosteroid spray (INS). METHODS: Data were pooled from two randomized, 24-week (16-week, double-blind + 8-week, open-label), placebo-controlled studies (NAVIGATE I and II). Results for patients receiving EDS-FLU (186 µg [n = 161] or 372 µg [n = 160]) or EDS-placebo (n = 161) twice daily during the double-blind phase are described. Responder criteria included NP grade reduction (≥1-point), 22-item Sino-Nasal Outcome Test (SNOT-22) reduction (>12-points), Patient Global Impression of Change (PGIC) (much/very much improved), and congestion score improvement (>0.5-points). RESULTS: More patients in the EDS-FLU group responded to each of the four responder criteria compared with EDS-placebo. More patients receiving EDS-FLU responded to ≥ 1 criterion compared with EDS-placebo at week 4 (82.7% and 60.4%, respectively) and week 16 (95.7% and 80.3%, respectively). Patients responded similarly irrespective of prior sinus surgery or prior INS use. Patient-reported outcome measures showed earlier responses than NP scores. CONCLUSIONS: Meaningful improvements were seen across multiple response criteria with EDS-FLU, suggesting that the broad treatment effect of EDS-FLU includes objective reduction in polyp grade and improvements in several patient-reported outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NAVIGATE I: NCT01622569 and NAVIGATE II: NCT01624662).

Bioavailability of oral carisoprodol 250 and 350 mg and metabolism to meprobamate: A single-dose crossover study.

BACKGROUND: Carisoprodol is a skeletal muscle relaxant indicated for use in the treatment of acute, painful musculoskeletal conditions. Two randomized, controlled clinical trials have reported that carisoprodol 250 mg QID was equally effective as and better tolerated than carisoprodol 350 mg QID. OBJECTIVES: The primary objective of the current study was to determine the relative bioavailability of carisoprodol and its metabolite, meprobamate, with singledose administration of 250- and 350-mg tablets. A secondary objective of the study was to determine whether lowering the carisoprodol dose would decrease plasma meprobamate concentrations. METHODS: This single-dose, randomized, open-label, crossover study enrolled healthy volunteers. Each dose was administered with water in the morning; after a 7-day washout, subjects received the alternate dose. Blood samples were drawn at prespecified times over a 48-hour period. For tolerability assessment, subjects underwent a physical examination, including 12-lead ECG. RESULTS: A total of 24 subjects were enrolled (12 men, 12 women; mean age, 22.8 years). The dose-adjusted AUC0-∞ values for carisoprodol were 5.29 µg/mL/h with the 250-mg tablet and 5.75 µg/mL/h with the 350-mg tablet (relative bioavailability, 92%). The mean (SD) Cmax values of carisoprodol and meprobamate after administration of the 250-mg carisoprodol tablet were 1.24 (0.49) and 1.84 (0.31) µg/mL, respectively, compared with 1.78 (0.97) and 2.46 (0.47) µg/mL with the 350-mg tablet. AUC0-∞ was dose proportional, and the apparent t1/2 values at the terminal phase were 1.74 hours with the 250-mg tablet and 1.96 hours with the 350-mg tablet. There were 3 mild adverse events considered possibly treatment related (weakness, dizziness, and drowsiness); these were reported in 2 subjects with 350-mg carisoprodol. CONCLUSIONS: In this small study in healthy fasting subjects, the exposure to carisoprodol and meprobamate was dose proportional between the single 250- and 350-mg doses. Both doses were generally well tolerated.

Efficacy and safety of azelastine 0.15% nasal spray administered once daily in subjects with seasonal allergic rhinitis.

Azelastine nasal spray is commercially available as a 0.1% w/v solution and is recommended for twice-daily dosing. Increasing the azelastine concentration to 0.15% may be effective with once-daily dosing without increasing the incidence of adverse events. This study evaluated the efficacy and safety of azelastine 0.15% nasal spray at a dosage of 2 sprays/nostril once daily. This randomized, double-blind, placebo-controlled study was conducted in subjects with moderate-to-severe seasonal allergic rhinitis (SAR) during the 2007/2008 Texas Mountain Cedar season. In total, 536 subjects were randomized to 2 sprays/nostril once daily (A.M.) of azelastine 0.15% or placebo. The primary efficacy variable was change from baseline in a 12-hour reflective Total Nasal Symptom Score (TNSS), consisting of nasal congestion, runny nose, itchy nose, and sneezing. The key secondary variable was change from baseline in 24-hour instantaneous TNSS, which determines the duration of action and effective dosing interval. After 2 weeks, the mean improvement in 12-hour reflective TNSS and percentage improvement in 12-hour reflective TNSS were significant (p < 0.001) with azelastine 0.15% (19%) compared with placebo (10%). The improvement in 24-hour instantaneous TNSS also was significant (p < 0.001) for azelastine 0.15% compared with placebo, supporting efficacy with once-daily dosing. All individual TNSS symptoms were significantly (p < 0.01) improved with azelastine 0.15% compared with placebo. With the exception of bitter taste (4.5%) and nasal discomfort (4.5%), adverse events with azelastine 0.15% were reported with an incidence similar to placebo. Azelastine 0.15% nasal spray was effective and well tolerated in subjects with SAR with once-daily dosing.

Efficacy and safety of azelastine 0.15% nasal spray and azelastine 0.10% nasal spray in patients with seasonal allergic rhinitis.

Azelastine is a second-generation antihistamine approved for treatment of allergic rhinitis. This randomized, double-blind, placebo- and active-controlled, parallel-group clinical trial evaluated the efficacy and safety of azelastine 0.15% and azelastine 0.10% nasal spray at a dosage of 2 sprays/nostril twice daily in patients with moderate-to-severe seasonal allergic rhinitis (SAR). In total, 526 patients were randomized 1:1:1 to treatment with 2 sprays/nostril twice daily of azelastine 0.15%, azelastine 0.10%, or placebo. The primary efficacy variable was change from baseline in 12-hour reflective Total Nasal Symptom Score (TNSS; A.M. and P.M. combined), consisting of nasal congestion, rhinorrhea, itchy nose, and sneezing. After 2 weeks, the mean improvement and percentage improvement in the 12-hour reflective TNSS were significant (p < 0.001) with azelastine 0.15% and azelastine 0.10% compared with placebo. In a retrospective analysis, there was a statistical difference (p = 0.047) in the mean improvement versus placebo in the 12-hour reflective TNSS with azelastine 0.15% compared with azelastine 0.10%. Onset of action with azelastine 0.15% was within 30 minutes. Bitter taste was the most common adverse event with both azelastine 0.15% and azelastine 0.10% (8.4% and 9.4% of patients, respectively). Somnolence was reported by 1.7% of patients treated with azelastine 0.15%, 0.6% of patients treated with azelastine 0.10%, and 0.6% of patients treated with placebo. Azelastine 0.15% nasal spray at 2 sprays/nostril twice daily significantly improved the nasal symptoms associated with SAR with an onset of action within 30 minutes and was well tolerated.

Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis.

BACKGROUND: Azelastine nasal spray and oral cetirizine are selective histamine H(1)-receptor antagonists that are approved in the United States for the treatment of seasonal allergic rhinitis (SAR). OBJECTIVE: The objective of the present study was to compare the efficacy and tolerability of azelastine nasal spray administered at the recommended dosage of 2 sprays per nostril twice daily with those of cetirizine in the treatment of moderate to severe SAR. METHODS: This multicenter, randomized, double-blind, parallel-group, 2-week comparative study was conducted during the 2004 fall allergy season in patients with moderate to severe SAR. After a 1-week placebo lead-in period, patients were randomized to receive azelastine nasal spray 2 sprays per nostril twice daily plus placebo tablets or cetirizine 10-mg tablets once daily plus a placebo saline nasal spray for the 2-week double-blind treatment period. The primary efficacy variables were (1) change from baseline to day 14 in the 12-hour reflective total nasal symptom score (TNSS), which combines scores for rhinorrhea, sneezing, itchy nose, and nasal congestion, and (2) onset of action, based on the instantaneous TNSS over 4 hours after the first dose of study drug. During the double-blind treatment period, patients recorded their symptom scores on diary cards twice daily (morning and evening). Patients aged > or =18 years also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at baseline and on day 14. RESULTS: Three hundred seven patients were randomized to treatment, and 299 completed 2 weeks of study treatment. The age of the population ranged from 12 to 74 years (mean, 35 years), 62.9% were female, and 69.6% were white. Over 2 weeks of treatment, both groups had significant improvements in the TNSS compared with baseline (P < 0.001). The overall change in TNSS was significantly greater with azelastine nasal spray compared with cetirizine (29.3% vs 23.0% improvement, respectively; P = 0.015). In terms of onset of action, azelastine nasal spray significantly improved the instantaneous TNSS compared with cetirizine at 60 and 240 minutes after the initial dose (both, P = 0.040). Scores on each domain of the RQLQ were significantly improved in both groups compared with baseline (P < 0.001); the overall RQLQ score was significantly improved with azelastine nasal spray compared with cetirizine (P = 0.049). Both treatments were well tolerated. CONCLUSION: In this 2-week study in patients with moderate to severe SAR, azelastine nasal spray was well tolerated and produced significantly greater improvements in TNSS and total RQLQ score compared with cetirizine.

Primary glycogen-rich clear cell squamous cell carcinoma of the mandibular gingiva.

Clear cell squamous cell carcinoma (CCSCC) is a rare variant of squamous cell carcinoma, first reported by Kuo, who described 6 cases of squamous cell carcinoma of the skin of the head and neck. CCSCC is composed of cells with clear cytoplasm, which Kuo attributed to the accumulation of intracellular fluid and not the presence of glycogen, lipid, or mucin. This case describes a 59-year-old woman who presented with an exophytic, hemorrhagic lesion on the posterior mandibular gingiva of 2 months' duration. Histologic examination revealed dysplastic stratified squamous epithelium showing transition to an infiltrating tumor composed of islands of epithelial cells with clear cytoplasm. The cytoplasm stained positive with periodic acid Schiff but was diastase labile. Mucicarmine stains were negative for intracytoplasmic mucin. This is the first reported case describing primary glycogen-rich CCSCC of the mandibular gingiva.

Efficacy and safety of azelastine 0.15% nasal spray administered once daily in patients with allergy to Texas mountain cedar pollen.

BACKGROUND: A previous study with azelastine nasal spray in patients with seasonal allergic rhinitis (SAR) demonstrated that increasing the azelastine concentration from 0.1% to 0.15% allowed for once-daily dosing without increasing the incidence of adverse effects. This study evaluated the efficacy of azelastine 0.15% nasal spray administered once daily for treating symptoms of SAR. METHODS: In this 14-day, randomized, double-blind, placebo-controlled study, patients with moderate-to-severe SAR were randomized to azelastine 0.15% (n = 251) or placebo (n = 255), both at a dosage of 2 sprays/nostril once daily. The primary efficacy variable was change from baseline in the 12-hour reflective Total Nasal Symptom Score (TNSS). Key secondary variables were change from baseline in 24-hour instantaneous TNSS, to establish the dosing interval, and change from baseline in the Total Ocular Symptom Score (TOSS). RESULTS: The mean improvement (3.57) and percentage improvement (19.3%) in 12-hour reflective TNSS was significant (p < 0.012) with azelastine 0.15% compared to placebo (2.14 and 11.4%, respectively). The mean improvement in 24-hour instantaneous TNSS was also significant (p < 0.001) for azelastine 0.15% compared to placebo, indicating efficacy with once-daily dosing. The overall improvement and percentage improvement in TOSS was significant (p ≤ 0.012) with azelastine 0.15% (2.21 and 16.7%, respectively) compared to placebo (1.28 and 6.0%, respectively). The overall score for the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was significantly (p < 0.001) improved from baseline in the azelastine group compared with the placebo group. Nasal discomfort (3.6%) and bitter taste (2.4%) were the most common adverse events. There were no reports of somnolence with azelastine. CONCLUSION: Azelastine 0.15% was effective and well tolerated with once-daily dosing. Azelastine 0.15% nasal spray significantly improved a complex of eye symptoms compared to placebo.

Randomized, double-blind trial of carisoprodol 250 mg compared with placebo and carisoprodol 350 mg for the treatment of low back spasm.

BACKGROUND: Carisoprodol, a centrally active skeletal muscle relaxant, is widely used for the treatment of acute, painful musculoskeletal disorders. When administered at a dose of 350 mg four times daily, carisoprodol demonstrated significant clinical benefit in its early clinical development trials; however, some unfavorable side effects, such as drowsiness and dizziness, were reported. Recently, research was conducted to determine if a lower dose of carisoprodol would retain efficacy but improve tolerability compared to the higher 350-mg dose. OBJECTIVE: The purpose of this multicenter study was to compare the efficacy and safety of carisoprodol 250-mg tablets four times daily to 350-mg tablets four times daily and to placebo in patients with acute, painful musculoskeletal spasm of the lower back. RESEARCH DESIGN AND METHODS: In this 1-week double-blind, placebo-controlled, parallel-group multicenter trial, patients 18 to 65 years of age with moderate to severe back spasm were randomly assigned to treatment with carisoprodol 250-mg tablets (n = 264), 350-mg tablets (n = 273), or matching placebo tablets (n = 269) three times daily and at bedtime. MAIN OUTCOME MEASURES: The coprimary efficacy variables were patient-rated relief from starting backache and patient-rated global impression of change assessed on treatment day 3. RESULTS: The carisoprodol 250-mg regimen was significantly more effective than placebo as assessed by both patient-rated relief from starting backache (p = 0.0001) and patient-rated global impression of change (p = 0.0046). There were no significant differences between the 250-mg and 350-mg dosages for the coprimary efficacy endpoints, and patients improved with or without sedation. Fewer than 1% of patients in the carisoprodol 250-mg group discontinued prematurely because of treatment-emergent adverse events, and no patient discontinued because of drowsiness. CONCLUSIONS: When administered three times daily and at bedtime, carisoprodol 250 mg was as effective as 350 mg three times daily and at bedtime with a lower incidence of adverse events and fewer discontinuations of therapy due to adverse events. Patients improved whether or not they reported sedation as an adverse event.

Double-blind, placebo-controlled study of azelastine and fluticasone in a single nasal spray delivery device.

BACKGROUND: A proof-of-concept study suggested that combination therapy with commercial azelastine hydrochloride nasal spray and fluticasone propionate nasal spray significantly improved nasal symptoms of seasonal allergic rhinitis compared with either agent alone. OBJECTIVE: To compare an azelastine-fluticasone combination nasal spray administered in a single-delivery device with a commercially available azelastine nasal spray and fluticasone nasal spray. METHODS: This 14-day, multicenter, randomized, double-blind study was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in, 610 patients with moderate-to-severe nasal symptoms were randomized to treatment with (1) azelastine nasal spray, (2) fluticasone nasal spray, (3) combination azelastine and fluticasone nasal spray, or (4) placebo nasal spray. All treatments were given as 1 spray per nostril twice daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of nasal congestion, runny nose, itchy nose, and sneezing. RESULTS: All 3 active groups were statistically superior (P