Optimal dose selection of fluticasone furoate nasal spray for the treatment of seasonal allergic rhinitis in adults and adolescents

Central Texas Health Research, نیو برانفلز، تگزاس, Texas, United States
Allergy and Asthma Proceedings (Impact Factor: 3.06). 03/2007; 28(2):216-25. DOI: 10.2500/aap.2007.28.2983
Source: PubMed


Efficacy and safety of fluticasone furoate nasal spray, administered using a unique side-actuated device, were evaluated in patients > or =12 years of age with seasonal allergic rhinitis to determine the optimal dose. A randomized, double-blind, parallel-group, placebo-controlled, dose-ranging study was performed on 641 patients who received placebo (n=128) or fluticasone furoate, 55 microg (n=127), 110 microg (n=127), 220 microg (n=129), or 440 microg (n=130), once daily for 2 weeks. Fluticasone furoate was significantly more effective than placebo for mean changes from baseline over the 2-week treatment period in daily reflective total nasal symptom score (primary end point; p < 0.001 each dose vs. placebo), morning predose instantaneous total nasal symptom score (p < 0.001 each dose versus placebo), daily reflective total ocular symptom score (p < or = 0.013 each dose versus placebo), and morning predose instantaneous total ocular symptom score (p < or = 0.019 for three highest doses versus placebo). The onset of action for fluticasone furoate nasal spray versus placebo was observed 8 hours after the first. dose of study medication in the 110 and 440 microg treatment groups (p < or = 0.032). The incidence of adverse events, results of clinical laboratory tests, and changes in 24-hour urinary cortisol values were similar between active treatment groups and placebo. The preliminary profile of fluticasone furoate is that of a rapidly effective therapy that confers 24-hour efficacy for both nasal and ocular symptoms with once-daily dosing. The 110-microg dose was chosen for phase III development because it achieved statistically significant and clinically meaningful results for all efficacy end points and provided the optimal risk-benefit ratio.

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    • "Comparison of once-daily intranasal fluticasone furoate with placebo in subjects with seasonal allergic rhinitis who had moderate-to-severe total ocular symptom scores at baseline concluded that mean reductions from baseline were significantly greater with fluticasone furoate than with placebo for total ocular symptom scores and each of the individual ocular symptoms[33]. Two other published studies support this conclusion[34,35]. "
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    ABSTRACT: Allergic rhinitis is a common disorder and involves the reaction to environmental allergens with resultant nasal and eye symptoms. The pathophysiologic mechanisms of the eye symptoms in allergic conjunctivitis include a direct effect on the eye by deposited allergen and indirect effects related to the deposition of allergen in the nasal mucosa. One of these proposed mechanisms is the existence of a nasal-ocular reflex whereby the nasal allergic reaction leads to an afferent reflex response, the efferent limb of which results in eye symptoms. Among the treatments available for allergic rhinitis, intranasal steroids are most efficacious for nasal symptoms and have also shown sizeable efficacy related to eye symptoms. We speculated that the effect of intranasal steroids on eye symptoms in allergic rhinitis was related to their inhibition of the nasal-ocular reflex and present data previously generated from our laboratory to support this assumption in a nasal challenge model.
    World Allergy Organization Journal 01/2011; 4(1 Suppl):S1-5. DOI:10.1097/WOX.0b013e3181f32dcd
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    • "Four double-blind placebo-controlled studies have been conducted on FF in adults and children over 12 years of age with SAR. One was a dose ranging study to evaluate the efficacy and safety of FF at 55 μg, 110 μg, 220 μg and 440 μg once daily in the US mountain cedar pollen season.60 Although all doses other than 55 μg demonstrated similar clinical efficacy that was statistically significant compared to placebo, it was the 110 μg dose that was thought to offer the optimal therapeutic ratio and was chosen for further clinical evaluation. "
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    ABSTRACT: Seasonal allergic rhinitis (SAR) is increasing in prevalence such that 1 in 4 persons is affected in the UK. It represents a considerable burden of disease since in a significant proportion of individuals the severity of nasal-ocular symptoms has an important effect on daily activity, performance and quality of life. Intranasal steroids (INS) form the mainstay of treatment, having been shown in meta-analyses to be superior to oral antihistamines, intranasal antihistamines and anti-leukotrienes. Fluticasone propionate is an established INS for the treatment of rhinitis, including SAR. Its favorable pharmacological profile combining high local efficacy with low systemic bioavailability has established fluticasone propionate as an effective intervention. The more recent introduction of structurally related fluticasone furoate with similar but enhanced pharmacological characteristics with a novel delivery device may confer further therapeutic advantages.
    Journal of Asthma and Allergy 06/2010; 3:19-28.
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    • "After single- and multiple-dose intranasal administration, plasma fluticasone furoate concentrations are below the lower limit of quantification in most patients (Allen et al 2007; Hughes et al 2007; Martin 2007). One study showed that only 2% of samples from patients receiving 110 μg of FF had quantifiable plasma drug concentrations (Martin 2007). "
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    ABSTRACT: Allergic rhinitis (AR) is a prevalent disease with great morbidity and significant societal and economic burden. Intranasal corticosteroids are recommended as first-line therapy for patients with moderate-to-severe disease, especially when nasal congestion is a major component of symptoms. To compare the efficacy and safety profile of different available intranasal corticosteroids for the treatment of AR, it is important to understand their different structures and pharmacokinetic and pharmacodynamic properties. Knowledge of these drugs has increased tremendously over the last decade. Studies have elucidated mechanisms of action, pharmacologic properties, and the clinical impact of these drugs in allergic respiratory diseases. Although the existing intranasal corticosteroids are already highly efficient, the introduction of further improved formulations with a better efficacy/safety profile is always desired. Fluticasone furoate nasal spray is a new topical corticosteroid, with enhanced-affinity and a unique side-actuated delivery device. As it has high topical potency and low potential for systemic effects, it is a good candidate for rhinitis treatment.
    Therapeutics and Clinical Risk Management 05/2008; 4(2):465-72. · 1.47 Impact Factor
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