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Background: Intranasal corticosteroids are generally considered the most effective medication class for controlling allergic rhinitis. Previous comparative studies with oral antihistamines have been only partially informative due to a variety of variables encountered during their execution., Objective: To compare fluticasone propionate nasal spray (FPNS) with the second-generation antihistamine cetirizine (oral tablet) and with placebo in a head-to-head study in a 2-week treatment study during fall ragweed season., Methods: A total of 978 subjects were screened for this study. Six hundred and eighty-two subjects were randomized into the study (170 subjects, FPNS 200 mcg once daily; 170, cetirizine 10 mg once daily; 171, FPNS placebo; 171, cetirizine placebo) and comprised the intent-to-treat population. A 1-week placebo run-in was followed by a 2-week active treatment period during which time a total nasal symptom score (TNSS), total ocular symptom score, and the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire were collected., Results: The primary efficacy end point was the mean change from baseline over the entire treatment period in A.M. reflective TNSS. The TNSS was the sum of the four individual nasal congestion, nasal itching, rhinorrhea, and sneezing scores, in which each symptom was scored on a scale of 0 to 3. Both FPNS and cetirizine improved the primary end point when compared with placebo during the active treatment period. Although there was a trend that favored FPNS with regard to the primary and secondary end points, there was not a statistical difference between the two treatments., Conclusion: FPNS and cetirizine were equally effective in treating fall seasonal allergic rhinitis during a 2-week head-to-head treatment investigation. Clinical trial NCT01916226, www.clinicaltrials.gov.

Objective: To evaluate the efficacy of levocetirizine 5 mg once daily in reducing seasonal allergic rhinitis (SAR) symptoms in US adults., Research Design and Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults aged 18 to 65 years with SAR symptoms in the spring in the US. After a single-blind placebo run-in period, subjects received levocetirizine 5 mg or placebo once daily over 14 days. ClinicalTrials.gov registry no.: NCT00621959., Main Outcome Measures: Primary efficacy variable was the Total 5-Symptom Score (T5SS). Secondary variables included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS). Safety assessments were based on adverse events (AEs)., Results: The intent-to-treat population comprised 596 subjects (levocetirizine, n = 301; placebo, n = 295). Comparison of mean T5SS over the total treatment period showed a nonsignificant between-group difference (levocetirizine, 8.90 +/- 0.19; placebo, 9.04 +/- 0.19; adjusted mean difference, -0.14; p = 0.546). Levocetirizine showed numerical (mean RQLQ, WPAI-AS, ESS) and statistically superior differences (two domains within WPAI-AS) compared with placebo upon analysis of secondary efficacy variables. The incidence of treatment-emergent AEs was similar (levocetirizine, 23.9%; placebo, 24.4%). As the lack of efficacy was inconsistent with all previous levocetirizine studies, post hoc analyses were performed to assess the influence of pollen counts, geography, and other factors; however, no conclusive explanation could be identified., Conclusions: In this study, levocetirizine 5 mg QD was well tolerated but failed to show significant efficacy compared with placebo in a US adult population with SAR. This finding is inconsistent with all previous studies with levocetirizine and in contrast to a concurrently run, similarly designed US study. It reflects the importance of conducting duplicate studies as there is always a small but real risk of false negative results in clinical studies, irrespective of the methodologic quality.

Background: Levocetirizine, a second-generation antihistamine for symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria, has not been previously studied in US patients., Objective: To assess the efficacy and safety of levocetirizine in improving symptoms and health-related quality of life in US adults with seasonal allergic rhinitis (SAR)., Methods: This multicenter, double-blind trial randomized adults with SAR, sensitized to at least 1 grass allergen, to receive levocetirizine, 5 mg, or placebo once daily in the evening for 2 weeks. The primary end point was the 24-hour reflective Total 5-Symptom Score (T5SS; sum of rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) during the entire treatment period. Secondary assessments included the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS), each assessed at week 1, week 2, and the end of treatment., Results: The intent-to-treat population comprised 287 patients taking levocetirizine and 290 taking placebo, with no significant between-group differences at baseline. Levocetirizine resulted in significantly greater improvement from baseline vs placebo in the T5SS (P < .001), overall RQLQ score (P < .001), general and work-related WPAI-AS subscores (P < .05), and ESS score (P < .001). Overall incidence of treatment-emergent adverse events was 14.4% for levocetirizine and 18.4% for placebo. The incidence of somnolence and fatigue was 0.7% and 1.8% with levocetirizine and 1.0% and 0% with placebo, respectively., Conclusions: Levocetirizine was well tolerated and was significantly more effective than placebo in improving the naso-ocular symptoms and health-related quality of life in US patients with SAR.

Background: The onset of action of antihistamine-decongestant combinations is an important factor in the treatment of subjects with seasonal allergic rhinitis (SAR)., Objective: This was a pooled analysis of 2 published studies with identical designs investigating the onset of action of the combination of fexofenadine hydrochloride 60 mg/pseudoephedrine hydrochloride 120 mg (FEX60/PSE120) in subjects with moderate to severe SAR., Methods: Subjects aged 12 years received single doses of FEX60/PSE120 or placebo in 2 randomized, double-blind, placebo-controlled, parallel-group, allergen exposure unit studies and recorded their SAR symptoms on diary cards before dosing, at 15-minute intervals for 2 hours after dosing, and at 30-minute intervals for the next 4 hours. The primary efficacy end point was onset of action, assessed in terms of absolute change in the major symptom complex (MSC) score, which was the sum of scores for the individual symptoms of stuffy nose, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and sneezing. Secondary end points included the absolute and percent change in the total symptom complex (TSC) score (the sum of the MSC score plus the scores for nose blowing, sniffles, postnasal drip, and cough) and individual symptom scores. Treatment-emergent adverse events (TEAEs) were recorded. Analyses were performed on the modified intention-to-treat (mITT) population, which included all subjects who were randomized to treatment and took the single dose of study medication according to the protocol., Results: A total of 1693 subjects were screened in the 2 studies, and 786 were randomized (298 in study 1, 488 in study 2). Two subjects withdrew from study 2; therefore, the mITT population consisted of 784 subjects. Subjects' mean age was 33.4 years, and 64.4% were female. The onset of action of FEX60/PSE120 was 45 minutes; the least squares mean (SD) treatment difference in the change from baseline in absolute MSC score was 0.8 (0.31) (95% CI, 0.2-1.4; P = 0.008). All subsequent changes from baseline in MSC scores were statistically significant for FEX60/PSE120 compared with placebo (P < 0.001). The absolute and percent change in TSC score and the percent change in MSC score were significantly decreased at all time points from 45 minutes after dosing for FEX60/PSE120 compared with placebo (all, P < 0.05). Individual symptoms (mean of hours 1 to 5) also were significantly improved with FEX60/PSE120 compared with placebo (all, P < 0.05). TEAEs were reported by 2.3% (9/391) and 4.3% (17/393) of subjects receiving FEX60/PSE120 and placebo, respectively. The most commonly occurring TEAS in the FEX60/PSE120 and placebo groups was somnolence (n = 4 and n = 6, respectively)., Conclusion: In this pooled analysis of 2 allergen exposure unit studies, FEX60/PSE120 had an onset of action of 45 minutes and a sustained effect throughout the 6-hour study period in subjects with moderate to severe SAR.

Although antihistamine-decongestant combinations are frequently used for allergic rhinitis, published data about the onset of action of these combination agents are limited. This randomized, double-blind, placebo-controlled, parallel-group study investigated the onset of action, efficacy, and safety of fexofenadine HCl 60 mg/pseudoephedrine HCl 120 mg or placebo in patients with moderate-to-severe seasonal allergic rhinitis in an allergen exposure unit. Assessments included major symptom complex (MSC) score (sum of sneezing, itchy nose, runny nose, watery eyes, itchy eyes, itchy ears/throat, and stuffy nose), and total symptom complex (TSC) score (MSC symptoms plus nose blows, sniffles, postnasal drip, and cough). Onset of action was defined as the first time that two consecutive, statistically significant absolute changes in MSC scores from baseline were achieved for study drug relative to placebo. The onset of action for the combination was 60 minutes (mean absolute MSC change from baseline: -6.9 +/- 0.3 for the combination compared with -5.9 +/- 0.3 for placebo from a baseline of 17.0 and 16.8, respectively; p < 0.05) for the modified intention-to-treat population (n = 486). Reductions in absolute MSC scores were significantly greater with the combination than placebo at all subsequent time points (p < 0.01). The combination resulted in significantly greater reductions compared with placebo for percent MSC, absolute TSC, and percent TSC scores at 60 minutes postdose (all p < 0.05) and throughout the study (all p < 0.05). The incidence of adverse events was 1.6 and 3.3% for the combination and placebo, respectively. In conclusion, fexofenadine HCl 60 mg/pseudoephedrine HCl 120 mg is effective in the treatment of patients with moderate-to-severe seasonal AR, with an onset of action of 60 minutes and a good safety profile.

Objective: To compare product attributes, preferences, and expected compliance associated with triamcinolone acetonide aqueous (TAA-AQ), fluticasone propionate (FP), and mometasone furoate (MF) nasal sprays in patients with allergic rhinitis., Study Design and Setting: Data from 2 randomized, double-blind crossover studies with identical design were pooled (N = 215). Patients completed a 14-item sensory attributes questionnaire immediately after each product, and stated their preference and expected compliance with a prescription after receiving all products., Results: Compared with FP and MF, TAA-AQ was associated with significantly less odor and greater liking of odor ( P < 0.001); and less taste, less dryness of nose/throat, less aftertaste, and greater overall liking ( P < 0.05). Significantly more patients preferred most a prescription of TAA-AQ (50.0%) versus FP (25.0%; P < 0.001) and MF (25.0%; P < 0.001), and would "definitely comply" with TAA-AQ (62.5%) versus FP (49.0%; P < 0.01) and MF (51.0%; P < 0.01)., Conclusion: TAA-AQ was associated with significantly more positive sensory attributes, higher preference, and better expected compliance than FP and MF., Significance: Patients' preferences for the sensory attributes of an intranasal corticosteroid may affect adherence to treatment.

Background: Sleep disturbances due to allergic rhinitis can contribute to daytime fatigue, impair mood, and decrease daytime functioning., Objective: To measure allergic rhinitis patients' nocturnal rhinitis-related quality of life using a new, validated disease-specific instrument, the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ)., Methods: This open-label study was conducted in a primary care setting. Adult patients with seasonal or perennial allergic rhinitis rated nocturnal rhinitis-related quality of life using the NRQLQ and sleep disturbances using the Pittsburgh Sleep Quality Index (PSQI) at baseline and after 3 weeks of treatment with triamcinolone acetonide aqueous nasal spray (TAA AQ), 220 microg/d. Changes from baseline in overall and individual domain scores for both the NRQLQ and PSQI were evaluated using t tests for paired differences., Results: The majority of the patients (N = 651) were female (58%), were white (85%), and shared a bed with a partner (63%). Mean +/- SD patient age was 45.7 +/- 15.5 years. TAA AQ treatment was associated with significant improvements in overall NRQLQ score (mean +/- SD change, -1.5 +/- 1.3; P < .001) and in individual domain scores (P < .001 for sleep problems, symptoms during sleep, symptoms upon waking in morning, and practical problems). Similarly, overall and individual PSQI domain scores were statistically significantly improved (P < .001). There were strong correlations between NRQLQ and PSQI scores (all comparisons P < .001)., Conclusions: Treatment with TAA AQ for 3 weeks resulted in statistically significant improvements in nocturnal rhinitis-related quality of life and sleep quality in allergic rhinitis patients treated in a primary care setting.

Domiciliary measurement of nasal peak inspiratory flow rate (nPIFR) provides a simple, noninvasive, objective assessment of nasal patency and may be useful for determining the effectiveness of therapeutic interventions. This randomized, parallel-group, investigator-blind study compared the effects of triamcinolone acetonide aqueous nasal spray (TAA AQ), 220 microg everyday (n = 19), and fluticasone propionate (FP AQ), 200 microg everyday (n = 20), for 21 days on nasal airflow in patients with seasonal allergic rhinitis (SAR), using domiciliary nPIFR. Patients had a > or = 2-year history of springtime SAR and positive epicutaneous or intradermal test to grass, tree pollen, or outdoor molds. nPIFR was measured three times each morning (before dosing) and at bedtime using an In-Check nPIF meter. All measurements were recorded on diary cards, and the best of the three measurements was used for data analysis. There were no significant demographic differences between treatment groups at baseline. Baseline nPIFR (+/- SE) was 106.5 L/minute (+/- 51.2) and 97.7 L/minute (+/- 45.0) in the TAA AQ and FP AQ groups, respectively (p = 0.5733). Model-based estimation of mean change from baseline with TAA AQ and FP AQ at the end of the study were 21.72 (+/- 6.04) and 16.48 (+/- 5.73), respectively. Both treatment groups showed an approximately 20% improvement in nPIFR versus baseline (p = 0.0002 and p = 0.0069 for TAA AQ and FP AQ, respectively), with no statistical difference between treatments. Weekly mean nPIFR scores indicated progressive improvement in nasal airflow with both treatments. Both TAA AQ and FP AQ were effective for improving nasal airflow as indicated by increases in nPIFR in patients with SAR.

Background: Previous studies have shown that fexofenadine and cetirizine effectively relieve symptoms of seasonal allergic rhinitis (SAR)., Objective: To compare the effects of fexofenadine hydrochloride, 180 mg, and cetirizine, 10 mg, on symptoms, drowsiness, and motivation in patients with moderate-to-severe SAR., Methods: In this 2-week multicenter, double-blind, randomized study, 495 subjects with moderate-to-severe SAR received once-daily fexofenadine hydrochloride, 180 mg, or cetirizine, 10 mg, without regard to food intake. Daily 12-hour reflective (AM, PM) and instantaneous (AM) individual symptoms and total symptom score (TSS) were evaluated. Drowsiness and motivation were recorded daily using visual analog scale at 7 AM, 10 AM, and 3 PM., Results: Between-treatment differences in reduction from baseline in AM instantaneous and 24-hour reflective TSS were -0.18 [95% confidence interval (CI), -0.55 to 0.20) and -0.22 (95% CI, -0.59 to 0.15), respectively. Since CIs for reduction in TSS between treatments fell within a 0.7 margin (defined a priori), treatments were considered statistically equivalent. Patients receiving fexofenadine experienced significantly less overall drowsiness vs baseline than those receiving cetirizine [-2.33 (95% CI, -3.80 to 0.86) vs 0.37 (95% CI, -1.10 to 1.84), P = .0110]. There was a trend toward greater improvements in overall motivation with fexofenadine compared with cetirizine [-2.36 (95% CI, -3.83 to 0.90) vs -0.30 (95% CI, -1.76 to 1.17), P = .0504]., Conclusions: Once-daily fexofenadine hydrochloride, 180 mg, given for 2 weeks caused statistically and clinically equivalent improvement in symptoms and significantly less drowsiness va baseline, compared with cetirizine, 10 mg, in patients with moderate-to-severe SAR.

Objective: We compared 220 microg daily intranasal aqueous triamcinolone acetonide (TAA AQ) with 200 microg daily fluticasone propionate (FP) for relief of seasonal allergic rhinitis symptoms. Study design and setting Randomized, parallel-group, investigator-blind study included patients with symptomatic seasonal allergic rhinitis. After a baseline period, TAA AQ or FP was taken for about 21 days. Nasal symptom (discharge, stuffiness, itching, sneezing) severity was recorded twice daily; total nasal symptom score was calculated. Health-related quality of life was assessed by Rhinoconjunctivitis Quality of Life Questionnaire., Results: Reductions in individual symptoms and total nasal symptom score were statistically significant versus baseline and were equivalent between treatments: -3.15 +/- 0.19 with TAA AQ (n = 148) and approximately 3.17 +/- 0.18 with FP (n = 147) (95% confidence interval for the difference, -0.7391 to 0.3693). Clinically and statistically significant improvements in Rhinoconjunctivitis Quality of Life Questionnaire scores were comparable., Conclusion: TAA AQ and FP were equally efficacious in relieving seasonal allergic rhinitis symptoms and improving health-related quality of life., Significance: Differences in molecular potency of intranasal steroids do not confer differences in efficacy.

Background: The topical potency of fluticasone propionate (FP) is known to be four times greater than that of triamcinolone acetonide (TAA). However, the significance of this difference has not been proven in the clinical treatment of seasonal allergic rhinitis (SAR)., Objective: To compare the efficacy, safety, and effect on health-related quality of life (HRQL) of FP and TAA aqueous nasal sprays in patients with SAR., Methods: Single-blind, parallel-group, active-controlled design. Patients were randomized to 3-week treatment with TAA 220 microg (n = 172) or FP 200 microg (n = 180) as two sprays/nostril once daily AM. Twelve-hour reflective symptom evaluations (nasal discharge, stuffiness, itching; sneezing; ocular itching/tearing/redness) were performed AM/PM, beginning at pretreatment baseline period. Incidences of specific treatment-related side effects were collected in daily questionnaires. HRQL was evaluated at baseline and end-of-treatment with a validated disease-specific, quality-of-life instrument., Results: TAA and FP produced similar improvement in daily total nasal symptom scores overall (49.4% and 52.7%, respectively; P = 0.332) and at every weekly time point (P > 0.05). There were no significant differences between TAA and FP in any individual symptom score at any time point except week 2 (FP provided greater reduction in sneezing, P = 0.046). No significant difference was found between groups in overall occurrence of specific treatment-related side effects. Overall Rhinoconjunctivitis Quality of Life Questionnaire scores were similar for TAA and FP at end-of-treatment., Conclusions: Despite differing molecular potencies, FP and TAA demonstrated comparable efficacy in the treatment of SAR, and produced similar occurrences of specific treatment-related side effects and similar improvements in overall patient HRQL.