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GSP301 is an investigational fixed-dose combination nasal spray of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid).To evaluate efficacy and safety of GSP301 in patients with seasonal AR (SAR).In this phase 2, double-blind, parallel-group study, patients (≥12 years of age) with SAR were equally randomized to twice-daily GSP301 (olopatadine 665 μg and mometasone 25 μg), once-daily GSP301 (olopatadine 665 μg and mometasone 50 μg), twice-daily or once-daily olopatadine monotherapy (665 μg), mometasone monotherapy (twice-daily 25 μg or once-daily 50 μg), or placebo for 14 days. The primary endpoint-mean change from baseline in morning and evening reflective Total Nasal Symptom Score (rTNSS)-was analyzed using analysis of covariance (ANCOVA; P.05 = statistically significant). Average morning and evening 12-hour instantaneous TNSS (iTNSS), ocular symptoms, individual symptoms, onset of action, quality of life, and adverse events (AEs) were also assessed.A total of 1111 patients were randomized. Twice-daily GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (P.001), twice-daily olopatadine (P = .049), and mometasone (P = .004). Similar significant improvements in iTNSS were observed with twice-daily GSP301 vs placebo (P.001) and twice-daily mometasone (P = .007); improvements were not significant vs olopatadine (P = .058). Once-daily GSP301 provided significant rTNSS and iTNSS improvements vs placebo and once-daily olopatadine (P.01, all) but improvements were not significant vs mometasone. Treatment-emergent AEs rates were 10.8%, 9.5%, and 8.2%, with twice-daily GSP301, once-daily GSP301, and placebo, respectively.Twice-daily GSP301 treatment was efficacious and well tolerated, providing statistically significant and clinically meaningful improvements in rTNSS (primary endpoint) vs placebo and both monotherapies.Clinicaltrials.gov Identifier NCT02318303.

Background Allergic rhinitis (AR) is an inflammatory condition of the nasal mucosa characterized by symptoms of nasal discharge, itching, sneezing, and congestion. Ocular symptoms are commonly associated with AR and include itching or burning, tearing or watering, and redness. Intranasal corticosteroids are a mainstay of treatment, and their effect on nasal symptoms is well described. Objective To demonstrate that a 14-day course of 200 μg/d of nasal fluticasone propionate is superior to placebo in relieving ocular symptoms associated with AR. Methods This was a randomized, double-blind, parallel group, multicenter study comparing 200 μg/d of fluticasone propionate with placebo in patients with seasonal allergic rhinitis. The primary end point was mean change from baseline in patient-rated reflective total ocular symptom score (rTOSS). Key secondary end points included mean change from baseline in the morning and evening rTOSS, end-of-treatment assessment of response, and effect on activities of daily living. The primary analysis was performed using analysis of covariance with a linear fixed-effects model. Results Fluticasone was statistically significantly more efficacious in reducing the ocular symptoms of AR than placebo. The least squares mean difference in the change from baseline of rTOSS was −0.36 ( P = .002). A statistically significant difference in mean change from baseline was observed in favor of fluticasone for morning and evening rTOSS. Significantly more patients taking fluticasone achieved an overall response compared with placebo. Fluticasone had a significantly greater effect on daily living activities and was well tolerated. Conclusion This study supports the efficacy of fluticasone in treating ocular symptoms associated with AR. Trial Registration clinicaltrials.gov Identifier: NCT01817790.

Background Antagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks. Methods A Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season. Both were prospective, randomized, double-blind, placebo- and active-referenced (cetirizine) studies. The Phase 2 trial assessed setipiprant 100–1000 mg b.i.d. and 1000 mg o.d. versus placebo in adult and elderly participants. The Phase 3 trial assessed setipiprant 1000 mg b.i.d. in adolescent, adult, and elderly participants. Efficacy was assessed using daytime nasal symptom scores (DNSS), night-time nasal symptom scores (NNSS) and daytime eye symptom scores (DESS). Results 579 participants were randomized in the Phase 2 trial (mean age 41.6–43.4 years); 630 were randomized in the Phase 3 trial (mean age 37.5–40.7 years). A statistically significant, dose-related improvement in mean change from baseline DNSS was observed over 2 weeks with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 trial (−0.15 [95% CI −0.29, −0.01]; p = 0.030). Setipiprant 1000 mg b.i.d. had no significant effect on this endpoint in the Phase 3 trial (−0.02 [95% CI −0.12, 0.07]; p = 0.652). Total and individual NNSS and DESS symptom scores were significantly improved with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 but not the Phase 3 trial. Setipiprant showed a favorable safety/tolerability profile. Conclusions The Phase 2 trial was the first large clinical study to assess a CRTH2 antagonist in seasonal AR in a real-life setting. Setipiprant dose-related efficacy in the Phase 2 trial was not confirmed during Phase 3. Setipiprant was well tolerated in both studies. Trial registration NCT01241214 and NCT01484119

Introduction Seasonal allergic rhinitis (SAR) symptoms are troublesome and may contribute to impaired quality of life (QoL). In a randomized, double-blind phase 2 study, fixed-dose combination of once-daily (QD) or twice-daily (BID) olopatadine hydrochloride/mometasone furoate nasal spray (GSP301) significantly improved average AM and PM reflective Total Nasal Symptom Scores (rTNSS; primary endpoint, presented elsewhere) vs placebo. Additional efficacy and QoL endpoints are reported here. Methods Patients with SAR (≥12 years; N=1,111) were equally randomized to GSP301 BID (olopatadine 665μg/mometasone 25μg), GSP301 QD (olopatadine 665μg/mometasone 50μg), olopatadine (665μg BID/QD), mometasone (25μg BID or 50μg QD), or placebo for 14 days. Mean change from baseline in average 12-hour AM and PM instantaneous TNSS (iTNSS), Physician-assessed Nasal Symptom Score (PNSS), and Rhinoconjunctivitis Quality of Life Questionnaire–Standardized Activities [RQLQ(S)] for GSP301 BID and QD vs placebo were analyzed using analysis of covariance (ANCOVA; P Results Compared with placebo, GSP301 BID and QD significantly improved iTNSS (least squares mean difference [97.5% CI] GSP301 BID: -1.11 [-1.65, -0.57]; QD: -1.11 [-1.64, -0.57]; PPPPP=0.005) vs placebo. Treatment-emergent AEs were 10.8%, 9.5%, and 8.2%, for GSP301 BID, QD, and placebo groups, respectively. Conclusions GSP301 BID and QD treatments provided statistically significant improvements in both SAR nasal symptoms and QoL vs placebo.

Background A new, hydrofluoroalkane nasal aerosol solution formulation of ciclesonide (CIC-HFA) delivered via a metered dose inhaler is currently in clinical development for treatment of allergic rhinitis. Objective To study tolerability and quality of life following administration of CIC-HFA 74- or 148-μg doses once-daily compared with placebo in patients with perennial allergic rhinitis (PAR) over 26 weeks. Methods Patients ≥12 years of age with a ≥2 year history of PAR were randomized in a placebo-controlled, double-blind, parallel group, multicenter study to CIC-HFA 74 μg, 148 μg, or placebo QD AM for 26 weeks. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs). Quality of life was assessed by using a rhinoconjunctivitis quality of life questionnaire with standardized activities (RQLQ[S]) in patients with baseline RQLQ ≥3.00. Reflective total nasal symptom scores (rTNSS) and instantaneous total nasal symptom scores (iTNSS) over 26 weeks were also evaluated. Results In this study, 1111 patients were randomized. The overall incidence of TEAEs was comparable between the treatment groups. Treatment with CIC-HFA 74- or 148-μg doses showed improvements in RQLQ[S] [least squares (LS) mean change 0.40 and 0.37, respectively from baseline, p < 0.01 versus placebo for both], rTNSS (LS mean change 0.65 and 0.52, respectively from baseline; p ≤ 0.01 versus placebo for both), and iTNSS (LS mean change 0.51 and 0.42, respectively from baseline; p < 0.05 versus placebo for both) from baseline. Conclusion In this study, once-daily treatment with CIC-HFA 74- or 148-μg doses over 26 weeks was well tolerated with comparable incidence of TEAEs between the treatment groups.

Nasal symptoms of allergic rhinitis are an important cause of sleep disturbance. Reduction of nasal symptoms, particularly nasal obstruction, has been linked to improvements in self-reported sleep quality. The enhanced-affinity intranasal corticosteroid fluticasone furoate and the oral antihistamine fexofenadine were compared with respect to nighttime symptoms of seasonal allergic rhinitis. In two randomized, double-blind, double-dummy, parallel-group studies, patients received fluticasone furoate nasal spray (FFNS),110 microg (study 1, n = 312; study 2, n = 224); fexofenadine, 180 mg (study 1, n = 311; study 2, n = 227); or placebo (study 1, n = 313; study 2, n = 229) once daily for 2 weeks. Fluticasone furoate was more effective (p < 0.001) than fexofenadine and placebo in both studies with respect to the mean changes from baseline over the treatment period in the nighttime symptoms score, nighttime reflective total nasal symptom score, predose instantaneous nasal symptom score, and morning peak nasal inspiratory flow. Fluticasone furoate was more effective than placebo (p

Seasonal allergic rhinitis (SAR) exerts a significant adverse impact on health-related quality of life (QoL) and productivity of those who suffer from it. Unfortunately, some therapies for SAR also have a negative impact. Therefore, it is important to scrutinize the influence of new SAR therapies on patients' QoL and ability to function. The purpose of this study was to evaluate the effect of a new nasal antihistamine, olopatadine, on QoL in SAR patients. In a multicenter, randomized, double-blind SAR study comparing olopatadine 0.6 and 0.4% to placebo nasal spray, patients completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at baseline and after 2 weeks of treatment. The RQLQ is a validated questionnaire that addresses overall QoL and 7 domains of impairment associated with rhinoconjunctivitis (activities, sleep, non--nose/eye allergy symptoms, practical problems, nasal symptoms, eye symptoms, and emotional impairment). The overall RQLQ mean changes from baseline with olopatadine 0.6% (-1.1 +/- 1.4) and 0.4% (-1.1 +/- 1.3) nasal sprays were superior (p < 0.05) to placebo (-0.8 +/- 1.2). Olopatadine spray 0.6% was superior to placebo in six of the seven RQLQ domains and olopatadine 0.4% was superior to placebo in five RQLQ domains (p < 0.05). The correlation between the olopatadine 0.6% mean total symptom scores and mean RQLQ score was r = 0.66 (p < 0.0001), indicating that the enhancement in QoL derived from olopatadine therapy was significantly associated with symptom reduction. Olopatadine nasal spray is an effective antiallergy medication that significantly improves the QoL of patients suffering from SAR.

Background A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR) to mountain cedar. Objective To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo nasal spray in patients with SAR to mountain cedar. Methods This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 12 to 81 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms. Results Olopatadine spray (0.4% and 0.6%) was statistically significantly superior to placebo for percentage change from baseline in overall reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and watery eyes. Olopatadine spray exhibited a safety profile comparable with that of placebo. Conclusions Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs and individual symptoms, including congestion, itchy and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to mountain cedar. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.

A new nasal aerosol solution formulation of ciclesonide containing a hydrofluoroalkane propellant (CIC-HFA) delivered via a metered-dose inhaler is currently in clinical development as a potential treatment for allergic rhinitis (AR). This study evaluated the efficacy and tolerability of CIC-HFA 74- or 148-microgram doses compared with placebo in patients with perennial AR (PAR). Patients ≥12 years of age with a ≥ 2-year history of PAR were randomized in a placebo-controlled, double-blind, parallel-group, multicenter study to CIC-HFA 74 micrograms, CIC-HFA 148 micrograms, or placebo q.d. in the morning (A.M.) for 26 weeks. Change from baseline in reflective total nasal symptom score (rTNSS), instantaneous total nasal symptom score (iTNSS), and rhinoconjunctivitis quality-of-life questionnaire with standardized activities (RQLQ[S]) in patients with baseline RQLQ of ≥3.00 were evaluated for the first 6 weeks of treatment. Treatment-emergent adverse events (TEAEs) were monitored throughout the study. Eleven hundred eleven patients were randomized. CIC-HFA 74- and 148-microgram doses showed statistically significant improvements in rTNSS (least squares [LS] mean change, 0.70 and 0.54, respectively; p ≤ 0.001 versus placebo for both), iTNSS (LS mean change, 0.58 and 0.42, respectively; p < 0.05 versus placebo for both), and RQLQ[S] (LS mean change, 0.55 and 0.37, respectively; p < 0.01 versus placebo for both) from baseline. The overall incidence of TEAEs was comparable between the CIC-HFA treatment groups and placebo. In this study, once-daily treatment with CIC-HFA 74- or 148-micrograms showed statistically significant improvements in nasal symptoms of PAR. Both doses were well tolerated. Clinical trial registration URL and registration number: www.clinicaltrials.gov/ct2/show/NCT00953147.

A hypotonic aqueous nasal spray of ciclesonide is indicated for the treatment of allergic rhinitis (AR). A new nasal aerosol formulation of ciclesonide containing a hydrofluoroalkane propellant delivered via a metered-dose inhaler (CIC-HFA) is currently in clinical development as a potential treatment for AR.To study the efficacy and safety of once-daily administration of CIC-HFA 80 or 160 μg compared with placebo in subjects 12 years and older with seasonal AR (SAR).Subjects 12 years and older with a ≥ 2-year history of SAR were randomized in a placebo-controlled, double-blind, parallel-group, multicenter study to receive CIC-HFA 80 or 160 μg or placebo once daily in the morning for 2 weeks. Changes from baseline in reflective total nasal symptom scores (rTNSSs), instantaneous TNSSs (iTNSSs), and reflective total ocular symptom scores (rTOSSs) in subjects with a baseline rTOSS of ≥ 5.00 were evaluated. Treatment-emergent adverse events were monitored throughout the study.Seven hundred seven subjects were randomized. From baseline, CIC-HFA 80 or 160 μg demonstrated 15.1% and 16.0% reductions in rTNSSs (P.0001, 3.7% for placebo), 14.3% and 15.4% reductions in iTNSSs (P.0001, 3.9% for placebo), and 15.7% and 15.0% reductions in rTOSSs (P.001, 6.8% for placebo). The overall incidence of treatment-emergent adverse events was low and comparable between the CIC-HFA and placebo groups.In this study, once-daily treatment with CIC-HFA 80 or 160 μg demonstrated statistically significant improvements in nasal and ocular symptoms of SAR. Both doses of active treatment were well tolerated.

Rationale This multicenter, randomized, double-blind placebo-controlled study was conducted to assess the efficacy and safety of two doses of olopatadine nasal spray as a treatment for SAR (Mountain Cedar season). Methods Patients assessed morning and evening reflective (refl) and instantaneous (inst) nasal and ocular symptoms including rhinorrhea, sneezing, itchy nose and congestion on a 0-3 scale. After a 3-21 day single blind placebo spray run-in period, 677 patients ages 12-81 with a minimum total nasal symptom score (TNSS) of 36 out of a possible 72 were randomized to olopatadine 0.4% (n=229), 0.6% (n=223), or placebo (n=225) 2 sprays/nostril BID for 2 weeks. Results Olopatadine HCl nasal spray 0.4% & 0.6% were significantly superior to placebo for percent change from baseline in overall refl (p=0.0002 & Conclusions Olopatadine HCl nasal spray 0.4% & 0.6% are well tolerated and provide statistically significant improvements in symptoms in patients with seasonal allergic rhinitis.

Background Ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) is currently in development as a potential treatment for allergic rhinitis. The objective of this study was to determine the efficacy and safety of CIC-HFA compared to placebo in subjects with perennial allergic rhinitis (PAR). Methods Subjects ≥12 years of age with a ≥2 year history of PAR were randomized in a placebo-controlled, double-blind, parallel group, multicenter study to CIC-HFA 74 μg (N = 298), CIC-HFA 148 μg (N = 505), or placebo (N = 307) QD AM for 26 weeks. Subject-reported change from baseline in the average of AM and PM reflective total nasal symptom score (rTNSS) and instantaneous total nasal symptom score (iTNSS) averaged over the first 6 weeks of treatment period were key endpoints and were calculated as a sum of the 4 individual nasal symptoms of congestion, runny nose, sneezing, and nasal itching each on a scale of 0 (no signs/symptoms evident) to 3 (severe symptoms). Change from baseline in the individual reflective and instantaneous nasal symptom scores over the first 6 weeks of treatment period were also evaluated. Treatment-emergent adverse events (TEAEs) were assessed throughout the study. Results CIC-HFA 74 μg and CIC-HFA 148 μg doses demonstrated a statistically significant improvement in rTNSS (LS mean change 0.70 & 0.54 respectively, P ≤ 0.001 for both), iTNSS (LS mean change 0.58 & 0.42 respectively, P ≤ 0.05 for both) and improvements in individual reflective and instantaneous nasal symptoms (P ≤ 0.05 for all, unadjusted for multiplicity) at 6 weeks from baseline. The overall incidence of TEAEs was low and comparable between the CIC treatment groups and placebo. The most frequently reported TEAEs (≥2% of subjects in any treatment group) were nausea, headache, sinus headache, cough, upper respiratory tract infection, instillation site discomfort, nasal discomfort, nasopharyngitis, sinusitis, oropharyngeal pain, and epistaxis. Conclusions In this study, once-daily treatment with CIC-HFA 74μg or CIC-HFA 148μg demonstrated statistically significant improvements in the nasal symptoms of PAR. Both active treatments were well tolerated.

Rationale Since SAR causes a considerable impact on QoL, the Rhinoconjunctivitis Quality of Life (RQLQ) Questionnaire was used to assess the QoL impact of olopatadine HCl nasal spray compared to the vehicle. Methods The 28-item RQLQ, consisting of 7 domains (activities, sleep, non-hayfever symptoms, practical problems, nasal symptoms, eye symptoms, and emotional), was used to collect QoL data during a multicenter, randomized, double-masked SAR (mountain cedar) trial comparing olopatadine HCl nasal spray, 0.6% and 0.4% against the olopatadine vehicle. Patients, recruited with at least a 2-yr history of non-recalcitrant SAR, filled out the questionnaire at baseline (randomization visit), and again after 2 weeks at the exit (end of treatment) visit. Results Olopatadine 0.6% (−1.1 + −1.4) and 0.4% (−1.1 + −1.3) nasal sprays were superior (p Conclusions Both olopatadine HCl nasal sprays are superior to vehicle in improving overall QoL. While patients receiving olopatadine HCl nasal spray, 0.6% had significantly demonstrable improvement in all areas of their life except non-hayfever symptoms, patients receiving olopatadine 0.4% nasal spray had significant improvement in 5 out of the 7 total QoL areas.