Background: GSP301 nasal spray is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). Objective: To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR). Methods: In this double-blind study, eligible patients (>= 12 years of age) with SAR were randomized 1:1:1:1 to twice-daily GSP301 (665 mu g of olopatadine and 25 mu g of mometasone), olopatadine (665 mu g), mometasone (25 mu g), or placebo for 14 days. The primary end point-mean change from baseline in average morning and evening 12-hour reflective Total Nasal Symptom Score (rTNSS)-was analyzed via a mixed-effect model repeated measures (P < .05 was considered to be statistically significant). Additional assessments included average morning and evening 12-hour instantaneous TNSS (iTNSS), ocular symptoms, individual symptoms, onset of action, quality of life, and adverse events (AEs). Results: A total of 1176 patients were randomized. GSP301 provided statistically significant and clinically meaningful rTNSS improvements vs placebo (least squares mean difference, -1.09; 95% CI, -1.49 to -0.69; P < .001) and vs olopatadine (P = .03) and mometasone (P = .02). Similar significant improvements in iTNSS were also observed with GSP301 (P <. 05 for all). Furthermore, GSP301 significantly improved overall ocular symptoms, individual nasal and ocular symptoms, and quality of life vs placebo (P <= .001 for all). Onset of action for GSP301 was observed within 15 minutes and was maintained at all subsequent timepoints. Treatment-emergent AEs occurred in 15.6%, 12.6%, 9.6%, and 9.5% of patients in the GSP301, olopatadine, mometasone, and placebo groups, respectively. Conclusion: GSP301 is efficacious and well tolerated vs placebo for treating SAR-associated nasal and ocular symptoms, with a rapid onset of action of 15 minutes in adult and adolescent patients 12 years and older. (C) 2019 American College of Allergy, Asthma & Immunology.

The relative rate and extent of systemic availability of beclomethasone-17-monopropionate (17-BMP; active metabolite of beclomethasone dipropionate) delivered via a BAI and MDI were compared.

A novel, inhalation-driven, multidose dry powder inhaler (MDPI) has been developed to deliver fluticasone propionate (Fp) and combination Fp and salmeterol (FS) more efficiently to the lungs than conventional inhalers.

MP29-02 (a novel intranasal formulation of azelastine hydrochloride [AZE] and fluticasone propionate [FP]) is more effective than commercially-available AZE or FP in controlling both nasal and ocular allergic rhinitis (AR) symptoms in patients with moderate-to-severe AR.1 Although significance over placebo (PLA) and active parameters is an essential proof of efficacy, clinical relevance is harder to judge, and is influenced by many patient-related factors such as predominant symptom. In clinical practice, patients frequently present with a predominant symptom. To mimic patient clinical presenting patterns, patients included in an MP29-02 clinical trial1 were categorized into four ‘types’ according to their predominant symptoms at baseline (i.e. congestion, itching, rhinorrhoea or sneezing predominants). Nasal congestion is frequently cited as the most bothersome nasal symptom,2 and is often difficult to control. It is associated with sleep-disordered breathing, which negatively impacts on patient quality of life, impairs productivity and increases daytime sleepiness causing tiredness and irritability and even anxiety and depression.3,4

Treatment of ocular symptoms associated with SAR was a secondary endpoint in the development program for MP29-02, a novel intranasal formulation of azelastine hydrochloride (AZ) and fluticasone propionate (FP). The key clinical efficacy and safety studies of MP29-02 (MP 4002 and 4004) were 2-week randomized, double-blind, placebo- and active-controlled trials in patients with moderate-to-severe SAR. The primary endpoint was change from baseline in the 12-hour reflective total nasal symptom score (rTNSS). The key secondary endpoint was the 12-hour reflective total ocular symptom score (rTOSS), consisting of itchy eyes, watery eyes, and eye redness. Symptom severity was scored twice daily on a 4-point scale (0 to 3; daily maximum 18). All treatments were administered 1 spray per nostril twice daily (AM and PM) in the same vehicle and delivery device. Total daily doses of AZ and FP were equivalent to marketed doses of 548 mcg and 200 mcg, respectively. A total of 1611 subjects were randomized and 1607 were included in the ITT population. MP29-02 was superior to placebo (P<.001) in both studies for improvement from baseline in rTOSS and either statistically or numerically superior to the single entity products. The mean rTOSS improvements with MP29-02 vs placebo were -3.07 points vs -1.90 (25.3% vs 15.6%) in study MP 4002 and -3.56 vs -2.02 (30.1% vs 17.8%) in study MP 4004. In addition to effective relief of nasal symptoms, MP29-02 significantly reduced the rTOSS compared to placebo in patients with moderate-to-severe SAR.

RATIONALE: Ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) is currently in development for the treatment for allergic rhinitis. The ability of CIC-HFA to relieve the ocular symptoms associated with seasonal allergic rhinitis (SAR) was evaluated in subjects ≥12 years of age. METHODS: Data for this analysis was collected as part of a placebo-controlled, double-blind, parallel group, multicenter study in subjects with a ≥2 year history of SAR randomized to CIC-HFA 80μg (N=226), CIC-HFA 160μg (N=225), or placebo (N=220) once-daily in the morning for 2 weeks. Change from baseline in reflective total ocular symptom score (rTOSS) averaged over the 2-week treatment period was a key secondary endpoint. Instantaneous total ocular symptom score (iTOSS) and individual reflective and instantaneous ocular symptom scores of tearing eyes, itchy eyes, and redness of eyes averaged over the 2-week treatment period were also evaluated. The rTOSS and iTOSS were recorded in the intent-to-treat subject population and were evaluated in subjects with baseline rTOSS≥5 (CIC-HFA 80μg:N=165, CIC-HFA 160μg:N=159, Placebo:N=161) and iTOSS≥5 (CIC-HFA 80μg:N=138, CIC-HFA 160μg:N=141, Placebo:N=146) respectively. RESULTS: CIC-HFA 80μg demonstrated a statistically significant improvement in rTOSS (P=0.0124). CIC-HFA 80μg and CIC-HFA 160μg demonstrated numerical improvements in iTOSS (P<0.05 for both, unadjusted for multiplicity) and individual reflective and instantaneous ocular symptom scores of tearing eyes, itchy eyes, and redness of eyes compared to placebo. CONCLUSIONS: In this study, once-daily treatment with CIC-HFA 80μg demonstrated statistically significant improvements in rTOSS. Numerical improvements in iTOSS and individual reflective and instantaneous ocular symptoms of SAR were observed with both CIC-HFA 80μg and CIC-HFA 160μg.

RATIONALE: Ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) is currently in development as a treatment for allergic rhinitis. Improvement in the rhinoconjunctivitis related quality of life associated with seasonal allergic rhinitis (SAR) was measured by the rhinoconjunctivitis quality of life questionnaire with standardized activities (RQLQ[S]) in subjects ≥12 years of age randomized to CIC-HFA or placebo. METHODS: Data was collected as part of a placebo-controlled, double-blind, parallel group, multicenter study during the Texas Mountain Cedar pollen season in subjects randomized to CIC-HFA 80μg (N=226), CIC-HFA 160μg (N=225), or placebo (N=220) once-daily in the morning for 2 weeks. Change in RQLQ[S] scores was recorded for the intent-to-treat population and calculated in subjects with baseline RQLQ[S] ≥3.0 (CIC-HFA 80μg:N=187, CIC-HFA 160μg:N=183, placebo:N=183). The RQLQ[S] was self-administered by subjects prior to randomization and at the end of the double-blind study medication period. Change from baseline in overall RQLQ[S], a key secondary endpoint, and in the individual domains of activities, sleep, non-nose/eye symptoms, practical problems, nasal symptoms, emotional, and eye symptoms over the 2-week treatment period were evaluated. RESULTS: CIC-HFA 80μg (P<0.0124) demonstrated statistically significant improvements and CIC-HFA 160μg demonstrated numerical improvements in overall RQLQ[S] (P-value not determined) and CIC-HFA 80μg and CIC-HFA 160μg demonstrated numerical improvements in individual domains of RQLQ[S] (P<0.05 for all, unadjusted for multiplicity) compared to placebo over the 2-week treatment period. CONCLUSIONS: In this study, once-daily treatment with CIC-HFA 80μg or CIC-HFA 160μg demonstrated improvements in the rhinoconjunctivitis related quality of life in subjects with SAR to Mountain Cedar pollen.

RATIONALE: A proof of concept study in patients with SAR indicated that combination therapy with commercially available azelastine nasal spray and commercially available fluticasone nasal spray significantly improved nasal symptoms compared to either agent alone. As a result, the current study was conducted with the combination of azelastine and fluticasone administered in a single delivery device. METHODS: The study was a randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe SAR conducted during the 2007/2008 Texas Mountain Cedar season. A total of 610 patients were randomized to treatment with: (1) azelastine (Astelin) nasal spray, (2) fluticasone (Flonase) nasal spray, (3) combination azelastine/fluticasone (MP 29-02) nasal spray, or (4) placebo nasal spray. All treatments were given 1 spray per nostril twice daily. The primary efficacy variable was the change from baseline in the 12-hour reflective total nasal symptom score (TNSS), consisting of nasal congestion, sneezing, itchy nose, and runny nose. RESULTS: All three active groups were statistically superior (P < .05) to placebo, and the combination was statistically superior (P < .001) to either agent alone. The TNSS improved 31.3% with combination azelastine/fluticasone, 20.8% with fluticasone, 16.3% with azelastine, and 9.0% with placebo. Dysgeusia (7.2%), epistaxis (3.9%), and headache (2.6%) were the only adverse events reported by more than 2% of patients treated with combination therapy. CONCLUSIONS: Therapy with azelastine nasal spray and fluticasone nasal spray in combination provided significant clinical benefit compared to either agent alone. Providing the two drugs in a single delivery device should benefit patients who require combination therapy to effectively manage their allergic rhinitis.