fluticasone-furoate and Rhinitis--Allergic--Seasonal

Although previous data suggest that intranasal fluticasone furoate (FF) improves ocular symptoms of allergic rhinitis (AR), it presents serious limitations that question its results and conclusions. Therefore, an independent systematic review with meta-analysis is required to confirm and clarify the magnitude of the effect of FF.. This review compared the efficacy of intranasal FF to placebo on ocular and nasal symptoms in patients with AR. Primary outcomes were reflective and instantaneous total ocular symptom scores (rTOSS and iTOSS), and reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS). Secondary outcomes included the assessment of response to therapy, quality of life (QoL), and adverse effects.. Sixteen trials (5.348 patients) were selected. Seven studies included seasonal AR patients and nine studies, perennial AR patients. Intranasal FF significantly improved rTOSS and iTOSS scores compared with placebo in patients with seasonal (weighted mean difference [WMD] -0.54, 95% CI, -0.70 to -0.37, and -0.59, 95% CI, -0.76 to -0.43) and perennial AR (-0.33, 95% CI, -0.31 to -0.05, and -0.38, 95% CI, -0.69 to -0.07). Intranasal FF was also significantly more effective in improving rTNSS and iTNSS scores in seasonal (WMD=-1.14, 95% CI, -1.57 to -0.72, and -1.32, 95% CI, -1.64 to -1.01) and perennial AR patients (-0.83, 95% CI, -1.08 to -0.59, and -0.90, 95% CI, -1.33 to -0.48). Finally, there were greater improvements in response to therapy and QoL with a favourable safety profile.. Intranasal FF showed a consistent ocular and nasal efficacy along with improvement in QoL in AR patients. This review provides significant evidence that treatment with FF nasal spray at a dose of 110 mcg once daily is effective in relieving ocular and nasal symptoms in adolescents and adults with AR.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Humans; Nasal Sprays; Placebos; Rhinitis, Allergic, Seasonal

Fluticasone furoate (FF) is the latest glucocorticoid officially approved for the treatment of allergic rhinitis. FF has shown the highest affinity and selectivity for the glucocorticoid receptors as well the longest tissue retention compared with other available intranasal steroids; these new pharmacologic characteristics provide the basis for its potent and prolonged anti-inflammatory activity at the target site.. A literature review achieved through PubMed and Medline research methods supports the clinical efficacy of FF versus placebo in reducing ocular and nasal symptoms related to allergic rhinitis (at the recommended starting doses of 110 μg once daily for adults and adolescents and 55 μg once daily for children), with a good safety profile. Moreover, the present review also compares FF with other intranasal steroids: FF represents a molecular evolution of fluticasone propionate (FP), and there is scientific evidence of therapeutic advantages over FP.. Fluticasone furoate is a promising molecule in the treatment of allergic rhinitis as it fits fully all the official guidelines' criteria. It is now being considered as a topical steroid that is quite close to the ideal pharmacological model for glucocorticoids due to its satisfying safety/tolerability profile, both in adults and children, leads FF to be considered as a topical steroid that is quite close to the ideal pharmacologic model for glucocorticoids. More studies should be directed to assess the improvement of quality of life in subjects with allergic rhinitis treated with FF, in comparison with other intranasal steroids and even H1-antihistamines; in addition, it could be also interesting to analyze eventual, additional effects of FF in patients with bronchial asthma, which is frequently associated with allergic rhinitis.

Topics: Androstadienes; Anti-Inflammatory Agents; Clinical Trials, Phase III as Topic; Humans; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Fluticasone furoate is a novel enhanced-affinity corticosteroid that has demonstrated favourable safety and tolerability in paediatric patients. Three pivotal phase III studies were conducted in children as young as 2 years of age; however, because the European Medicines Agency has recently approved fluticasone furoate for use in children aged>or=6 years, a subanalysis has been conducted to support safety and tolerability in the 6- to 11-year age group.. All three trials included in the subanalysis were randomized, double-blind, placebo-controlled, parallel-group studies: a 2-week US study in patients with seasonal allergic rhinitis (SAR), a 12-week global study in patients with perennial allergic rhinitis (PAR) and a 6-week US hypothalamic-pituitary-adrenal (HPA) axis safety study in patients with PAR. Randomized patients received once-daily treatment with either fluticasone furoate nasal spray (FFNS) 55 microg (n=297; 2-week SAR and 12-week PAR studies only), FFNS 110 microg (n=321) or vehicle placebo nasal spray (n=330). Safety assessments included clinical adverse event (AE) monitoring, clinical laboratory tests, detailed nasal examinations, monitoring of vital signs, and 12-lead ECGs. Ophthalmic examinations (12-week PAR study only) were conducted by an ophthalmologist or optometrist before randomization and at final treatment visit. Twenty-four-hour urinary cortisol (UC) excretions (6- and 12-week PAR studies) and serum cortisol (SC) concentrations (6-week PAR study only) were assessed at specified timepoints over 24 hours as a measure of HPA axis function. In the 6-week HPA axis safety study in patients with PAR, 24-hour UC and SC samples were collected in a domiciled (clinical) setting.. No unexpected safety results were observed in patients aged 6-11 years enrolled in the three studies. Across all three trials, AEs considered by the investigator to be drug related were observed in 10%, 7% and 8% of patients in the FFNS 55 microg, FFNS 110 microg and placebo groups, respectively. The most common AEs were headache (8%, 9% and 8% in the FFNS 55 microg, FFNS 110 microg and placebo groups, respectively), nasopharyngitis (5%, 6% and 5%, respectively), pharyngolaryngeal pain (5%, 3% and 4%, respectively), epistaxis (4% in both active treatment groups and 4% in the placebo group) and pyrexia (3% in both active treatment groups and 2% in the placebo group). Findings from nasal examinations were similar across the treatment and placebo groups. Ophthalmic examinations found no differences between the treatment groups for mean change from baseline in intraocular pressure (assessed in the 12-week PAR study only), and no posterior subcapsular cataracts were reported in patients in either FFNS-treatment group. In the 6-week HPA axis study, 24-hour SC geometric mean concentrations were similar for FFNS and placebo groups. The lower limit of two-sided 95% confidence interval (CI) for the treatment ratio was greater than the prespecified noninferiority margin of 0.8 (treatment ratio=0.92, 95% CI 0.80, 1.05).. FFNS has a favourable safety and tolerability profile in patients aged 6-11 years with PAR or SAR.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Aerosols; Androstadienes; Anti-Allergic Agents; Child; Female; Humans; Hydrocortisone; Male; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Fluticasone furoate is a novel glucocorticoid developed for the treatment of allergic rhinitis and other inflammatory diseases. Fluticasone furoate demonstrates high systemic clearance, low oral bioavailability and low absolute bioavailability after intranasal administration (<0.5%). The drug possesses a high receptor affinity. Fluticasone furoate is given once daily at a dose of 110 microg. Clinical studies tested the efficacy of fluticasone furoate in seasonal allergic rhinitis and perennial allergic rhinitis. Patients randomized to the drug experienced significant alleviation in their nasal and ocular symptoms as well as clinically relevant improvement in quality of life. The drug is well tolerated and has a good safety profile owing to reduced systemic exposure. Thus, fluticasone furoate might represent a single treatment option for nasal and ocular symptoms of allergic rhinitis.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Glucocorticoids; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Allergic rhinitis (AR) is a highly prevalent disorder, which often manifests as both nasal (congestion, sneezing, itching and rhinorrhoea) and ocular (redness, watery eyes, itching and burning) symptoms. Until recently, efficacy against the ocular symptoms of AR has been inconsistent for any single intranasal corticosteroid (INS). Fluticasone furoate is an enhanced-affinity glucocorticoid with potent anti-inflammatory activity.. To assess better the efficacy of an INS in the treatment of both the nasal and ocular symptoms of seasonal AR (SAR).. Data from all four trials of fluticasone furoate nasal spray (FFNS) in the treatment of SAR are reviewed and critically considered.. FFNS consistently and significantly improved the nasal and ocular symptoms of SAR in patients sensitised to several different seasonal allergens (grass, ragweed and mountain cedar pollen) in all trials. An integrated analysis of the results also confirmed improvements in both nasal and ocular symptom scores in previously under-represented adolescent patients treated with FFNS.. FFNS is the first INS to show consistent nasal and ocular efficacy across all SAR trials.

Topics: Administration, Intranasal; Adolescent; Androstadienes; Anti-Allergic Agents; Conjunctivitis, Allergic; Humans; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal

Fluticasone furoate nasal spray is a new topical intranasal corticosteroid with enhanced affinity for the glucocorticoid receptor and low systemic exposure, which was recently approved in the US for the treatment of seasonal or perennial allergic rhinitis in adults and in children aged >or=2 years. Fluticasone furoate nasal spray employs a novel delivery device with a unique side-actuated design, a short nozzle and a new trigger mechanism designed for ease of use. In well controlled clinical trials, intranasal fluticasone furoate 110microg once daily for 2 weeks in adults and adolescents with seasonal allergic rhinitis reduced nasal and ocular symptoms, and improved health-related quality of life to a significantly greater extent than placebo. Similarly, treatment with intranasal fluticasone furoate 110microg once daily for 4-6 weeks in adults and adolescents with perennial allergic rhinitis was superior to placebo in reducing nasal symptoms and with respect to overall response to therapy. In children aged 6-11 years, fluticasone furoate nasal spray was shown to be effective in reducing the nasal symptoms of seasonal and perennial allergic rhinitis following treatment for 2 and 4 weeks, respectively. Fluticasone furoate nasal spray was well tolerated in adults, adolescents and children aged 2-11 years, with an overall incidence of adverse events similar to that with placebo.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Equipment Design; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Devices for the aqueous delivery of intranasal corticosteroids to patients with allergic rhinitis have been available since 1984, so there is a need for new devices to be developed to provide ease of use, efficacy and safety. A novel drug delivery system has been developed for fluticasone furoate (FF; GlaxoSmithKline): a new enhanced-affinity glucocorticoid with a scent-free formulation. The FF system was developed, giving attention to patients' unmet needs, in order to promote acceptance and compliance. It demonstrates a number of key features including its ergonomic design, side-actuation system and short delivery nozzle. Exploiting issues with present devices highlighted the need for the FF system. This review reports data from key studies and surveys conducted by GlaxoSmithKline during development, to determine ease of use and acceptance of the FF system. Findings suggest that the FF system should aid in improving attitudes to the use of intranasal corticosteroids amongst physicians and patients.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Anti-Allergic Agents; Drug Delivery Systems; Humans; Patient Compliance; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Intranasal corticosteroid sprays (INCSs) are commonly used for therapy of allergic rhinitis (AR). Adherence to regular use of INCSs is influenced by patient perception and preferences of products. The study objective was to compare perceived sensory attributes of fluticasone furoate nasal spray (FFNS) and mometasone furoate nasal spray (MFNS) in AR patients.. In a multicenter, randomized, crossover, prospective study, 40 seasonal AR patients were administered both FFNS and MFNS for 2 weeks each in a crossover fashion, for a total of 4 weeks. Patients completed questionnaires for each product regarding perceived sensory attributes at the end of each two-week period of product administration.. FFNS was significantly preferred over MFNS. Significantly, fewer subjects perceived a bitter taste (p=0.01), medication running down their throat (p=0.033), and medication running out of their nose (p=0.002) with FFNS. MFNS was more frequently reported to induce nasal irritation (p=0.012), sneezing (p=0.017), and rhinorrhea (p=0.007) compared to FFNS. Interestingly, these findings were markedly observed in females. Medicine dripping out of the nose and nasal shooting were the most common problems reported for MFNS with a higher proportion of subjects who felt moderate-to-severe discomfort. Overall, 52.5% of patients expressed a preference for FFNS compared with 22.5% for MFNS.. Several perceived sensory attributes of FFNS were rated significantly superior to MFNS. FFNS may contribute to enhanced treatment outcomes in AR patients due to improved treatment adherence.

Topics: Administration, Intranasal; Adult; Aged; Androstadienes; Anti-Allergic Agents; Cross-Over Studies; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Sprays; Patient Preference; Rhinitis, Allergic, Seasonal; Sex Factors; Sneezing; Surveys and Questionnaires; Taste

Allergic rhinitis (AR) affects up to 30% of the adult population and symptomatic patients continue to engage in daily life activities, including car driving. Previous studies have shown that AR can impair cognitive functions, especially during longer-lasting tasks. Other reports suggest negative effects on psychomotor functions such as driving, but no clear evidence has been presented yet.. Primary objective was to determine the effect of AR per se on actual driving performance and compare it with the effects of treated AR.. Nineteen patients with documented AR history underwent a unique and validated 1-h on-the-road driving test outside the pollen season. In a 4-leg repeated measures design, patients underwent a nasal provocation test with either pollen or inactive control prior to the driving test. In the three conditions with pollen provocation, patients were pretreated with either cetirizine 10 mg, fluticasone furoate 27.5 μg, or placebo to alleviate the provoked AR symptoms.. The driving performance of patients when symptomatic and not treated was significantly impaired compared to the placebo condition. When engaging in a secondary memory task during driving, their performance deteriorated further. The magnitude of impairment was relevant and comparable to that seen at a blood alcohol level of 0.05%, the legal limit in many countries. Treatment of AR symptoms partially counteracted the effect of AR on driving.. Untreated AR can impair driving ability and put patients at risk. Drug therapy reduces this impairment, and AR patients should therefore be advised to always treat their condition.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Automobile Driving; Cetirizine; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Rhinitis, Allergic, Seasonal; Young Adult

Nasal allergen challenge (NAC) leads to a nasal ocular reflex, which is augmented by allergic inflammation. This study was designed to confirm our previous observation that an intranasal steroid inhibits the nasal ocular reflex and to show that histamine does not play an important role in the genesis of this reflex.. We performed a randomized, double-blind, double-dummy, placebo (PL)-controlled, four-way crossover trial in subjects with seasonal allergic rhinitis out of season. Subjects were randomized to receive 1 week pretreatment with intranasal PL and intraocular (PL/PL), intranasal PL and intraocular olopatadine (PL/OLO), intranasal fluticasone furoate (FF) and intraocular PL (FF/PL), and the combination (FF/OLO). Subjects then underwent NAC on 2 consecutive days. The number of sneezes and nasal and ocular symptoms were recorded, and levels of tryptase and histamine were measured in nasal lavages.. NAC after PL/PL resulted in increase in symptoms, histamine, and tryptase after the challenge on the 2nd day. There was a reduction in eye symptoms on the 2nd day of challenge from 6.0 after PL/PL to 0 after FF/PL (p = 0.001), 2.5 after PL/OLO (p = 0.3), and 1.5 after FF/OLO (p = 0.003). Furthermore, there was no significant difference between the response after FF/PL versus FF/OLO and a significant difference between FF/PL and PL/OLO (p = 0.02). Levels of tryptase followed a similar trend. The number of eosinophils in nasal lavages on the 2nd day of challenge were also reduced by the treatment arms containing FF compared with PL.. Our data confirm the existence of a nasal ocular reflex after NAC. OLO alone or the addition of OLO to FF does not impact ocular symptoms caused by the naso-ocular reflex, suggesting that mast cells are not activated to release histamine in the conjunctiva during this process.

Topics: Administration, Intranasal; Adult; Allergens; Androstadienes; Cross-Over Studies; Dibenzoxepins; Disease Progression; Drug Therapy, Combination; Eosinophils; Eye; Female; Histamine; Humans; Injections, Intraocular; Male; Middle Aged; Nose; Olopatadine Hydrochloride; Reflex; Rhinitis, Allergic, Seasonal; Young Adult

Allergic rhinitis and exercise induced bronchoconstriction (EIB) are common in asthmatic children. The aim of this study was to investigate whether treatment of allergic rhinitis with an intranasal corticosteroid protects against EIB in asthmatic children.. This was a double-blind, randomized, placebo-controlled, parallel group study. Subjects aged 12-17 years, with mild-to-moderate asthma, intermittent allergic rhinitis and ≥ 10% fall in FEV(1) at a screening exercise challenge were randomized to 22 ± 3 days treatment with intranasal fluticasone furoate or placebo. The primary outcome was change in exercise induced fall in FEV(1) . Secondary outcomes were changes in the area under the curve (AUC), asthma control questionnaire (ACQ), pediatric asthma quality of life questionnaire (PAQLQ), and exhaled nitric oxide (FeNO).. Twenty-five children completed the study. Mean exercise induced fall in FEV(1) (± SD) decreased significantly (95% CI: 0.7-18.2%, P = 0.04) in the fluticasone furoate group from 28.4 ± 15.8% to 19.0 ± 13.8%, compared to the placebo group (27.4 ± 16.0% to 27.4 ± 19.2%). The change in AUC was not significantly different between treatment groups. However, within the fluticasone furoate group the AUC decreased significantly (P = 0.01). Although total PAQLQ score did not improve, the activity limitation domain score improved significantly within the fluticasone furoate group (P = 0.03). No significant changes were observed in FeNO and ACQ.. Treatment of allergic rhinitis in asthmatic children with an intranasal corticosteroid reduces EIB and tends to improve quality of life.

Topics: Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma, Exercise-Induced; Child; Double-Blind Method; Exercise; Female; Forced Expiratory Volume; Humans; Male; Nasal Sprays; Nitric Oxide; Quality of Life; Rhinitis, Allergic, Seasonal

The mechanisms underlying conjunctival symptom reduction by nasal corticosteroids in allergic rhinoconjunctivitis are unknown. A naso-ocular reflex may be present.. To study the effects of nasal fluticasone furoate (FF) on conjunctival symptoms and substance P and histamine levels in tear fluid after nasal grass pollen provocation (GPP).. A double-blind placebo-controlled study was performed in 26 grass pollen-allergic patients. A selective GPP was performed during the grass pollen season after 2 weeks of FF or placebo treatment. Nasal and conjunctival symptoms were scored using a visual analog scale (VAS), and tear fluid was collected for measuring substance P and histamine using an enzyme-linked immunosorbent assay.. Compared with placebo, FF reduced conjunctival symptom scores during the pollen season (-1.75 [-2.75, 0.20] vs 0.0 [0.0, 0.0]; P = .01) and after GPP at 15 minutes (0.05 [-0.42, 1.52] vs 2.05 [0.62, 3.62]; P < .001) and 1 hour (-0.45 [-1.75, 0.1] vs 0.05 [-0.97, 1.85]; P < .01). Treatment with FF decreased substance P levels in tear fluid (44.11 [32.81, 61.02] vs 65.26 [48.62, 79.73] pg/mg protein; P = .0098). Histamine levels in tear fluid showed a GPP-induced increase in the placebo group (7.26 [3.12, 9.69] vs 5.71 [2.05, 7.00] ng/mg protein; P = .02), but not in the FF group (6.77 [3.43, 13.00] vs 5.24 [3.18, 7.06] ng/mg protein; P = .08).. FF nasal spray reduced conjunctival symptoms in grass pollen-allergic patients in parallel with lower substance P levels in tear fluid. These data help in understanding the reduction of conjunctival symptoms by intranasal anti-inflammatory therapy.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Androstadienes; Antigens, Plant; Conjunctiva; Conjunctivitis, Allergic; Female; Histamine; Humans; Male; Nasal Provocation Tests; Paranasal Sinuses; Poaceae; Pollen; Rhinitis, Allergic, Seasonal; Seasons; Substance P; Tears; Young Adult

Allergic rhinitis is a common upper respiratory tract inflammation associated with a significant morbidity in all the age groups. Fluticasone furoate is a new potent topical glucocorticoid for the treatment of allergic rhinitis.. To compare efficacy and safety of fluticasone furoate (FF) nasal spray 110 microg/day with fluticasone propionate (FP) nasal spray 200 microg/day for the relief of symptoms of allergic rhinitis in adult Indian patients.. Clinically symptomatic patients (n=220) with allergic rhinitis received treatment with FF or FP for 2 weeks in this comparative, open label, multicentric, clinical trial. Nasal symptoms (nasal congestion, rhinorrhea, nasal itching, and sneezing) and ocular symptoms (itching/burning eyes, tearing/watering eyes, and eye redness) were recorded on a 4-point categoric scale by the patients. The efficacy was assessed by the change in nasal and ocular symptom scores as their subtotals (Total Nasal Symptom Score and Total Ocular Symptom Score) and grand total (Total Symptom Score).. FF produced significantly better improvement in Total Symptom Score (-10.4 +/- 3.2 vs. -8.9 +/- 3.5, p<0.005) and Total Nasal Symptom Score (-7.3 +/- 2.2 vs. -6.2 +/- 2.6, p<0.005) as compared to FP. Also a significantly larger percentage of patients achieved complete symptomatic relief with FF (45.3% vs. 31.4%, p<0.05). FF was also better tolerated than FP.. FF nasal spray is significantly more effective and better tolerated than FP nasal spray for the treatment of allergic rhinitis in adult Indian patients.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Child; Dose-Response Relationship, Drug; Female; Fluticasone; Humans; India; Male; Middle Aged; Nasal Sprays; Rhinitis, Allergic, Seasonal; Treatment Outcome

Intranasal corticosteroids are first-line treatment for moderate-to-severe seasonal allergic rhinitis (AR).. To compare preferences for fluticasone furoate and fluticasone propionate nasal sprays after 1 week of treatment in patients with symptomatic seasonal AR.. Patients with seasonal AR were enrolled (n = 360) and randomized 1:1 to active treatment (fluticasone furoate, 110 microg, or fluticasone propionate, 200 microg, followed by crossover treatment for 1 week each) or matched placebo sequence with a 1-week washout before crossover dosing. Fluticasone furoate and fluticasone propionate efficacy was measured by change from baseline during 1 week in daily reflective total nasal symptom score (rTNSS) that assessed severity of rhinorrhea, nasal congestion, nasal itching, and sneezing. Patient preference for fluticasone furoate or fluticasone propionate was assessed at the end of the study by questionnaire.. Three hundred sixty patients from 29 clinical sites in the Unites States were randomized and treated between August 1, 2007 and November 30, 2007. Most patients were white (73%) and female (59%), with a mean age of 38.3 years, and had had seasonal AR for at least 10 years (74%). Fluticasone furoate and fluticasone propionate each reduced the daily rTNSS compared with their respective placebos (least squares mean [SD] difference, -0.8 [0.24], P < .001, and -0.6 [0.24], P = .01, respectively). More patients (P < .001) preferred fluticasone furoate to fluticasone propionate based on attributes of scent or odor (58% vs 27%), aftertaste (60% vs 18%), leaking out of the nose and down the throat (59% vs 21%), and mist gentleness (57% vs 26%). No statistically significant differences were seen in preferences regarding ease of use, delivery method, or device comfort.. Both fluticasone furoate and fluticasone propionate significantly improved symptoms in adult patients with seasonal AR. Most patients preferred the sensory attributes of fluticasone furoate to those of fluticasone propionate after 1 week of treatment.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Allergic Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Patient Preference; Placebos; Rhinitis, Allergic, Seasonal; Sensation; Smell; Surveys and Questionnaires; Taste; Treatment Outcome

The objective of this study was to evaluate the efficacy and safety of fluticasone furoate (FF) nasal spray 55 and 110 microg once daily in children with seasonal allergic rhinitis (SAR). Patients (n = 554) received placebo nasal spray or FF, administered using a unique side-actuated device, in a 2-wk, randomized, double-blind study. Symptoms were evaluated by patients using a 4-point categorical scale. Efficacy assessments included reflective and instantaneous total nasal symptom scores (r/iTNSS). Primary analyses were conducted in patients aged 6-11 yr in the intent-to-treat population (ITT); the 2-11 yr group provided supportive analyses. In patients aged 6-11 yr, FF 110 microg once daily significantly improved the daily rTNSS compared with placebo. FF 55 microg once daily was only numerically better for rTNSS and iTNSS. Secondary pre-dose iTNSS and overall response to therapy were significant with FF 110 microg. The significant findings for FF 110 microg were supported by analyses in the entire ITT population of 2-11 yr olds. Both doses of FF were well tolerated. These study results suggest that FF nasal spray administered once daily for 2 wk is well tolerated and effective for the treatment of SAR symptoms in children aged 2-11 yr.

Topics: Administration, Intranasal; Androstadienes; Child; Child, Preschool; Double-Blind Method; Female; Humans; Male; Rhinitis, Allergic, Seasonal

Fluticasone furoate (FF) is a novel enhanced-affinity corticosteroid for the treatment of allergic rhinitis, delivered by a unique side-actuated device. This study was designed to investigate the efficacy and safety of FF nasal spray (FFNS) 110 microg once daily compared with placebo in adults and adolescents (aged > or =12 years) with seasonal allergic rhinitis (SAR) symptoms caused by mountain cedar (Juniperus ashei) pollen.. This was a randomized, double-blind, placebo-controlled, parallel-group, phase III study conducted over a 2-week period (between 10 December 2004 and 19 January 2005) at seven study sites, in Austin, Texas, USA, and San Antonio, Texas, two metropolitan cities in the central Texas Hill Country located approximately 80 miles apart. Adult and adolescent patients (aged > or =12 years) with SAR, who were sensitized to mountain cedar (Juniperus ashei) pollen, were randomized to receive either FFNS 110 microg (n = 152) or placebo (n = 150) once daily. Patients rated the severity of each nasal symptom (rhinorrhea, nasal congestion, nasal itching, and sneezing) and ocular symptom (redness, watery eyes, itching and burning) on a 4-point categorical scale (0 = none, 3 = severe) in a reflective and instantaneous manner. Patients also rated their overall evaluation of response to therapy.. ClinicalTrials.gov Identifier NCT00115622.. FFNS significantly improved the nasal symptoms of SAR compared with placebo. The least square (LS) mean difference in the reflective total nasal symptom score (TNSS) was -0.777 (p = 0.003). A significant reduction in morning pre-dose instantaneous TNSS was also observed compared with placebo (LS mean difference -0.902; p < 0.001). Patients receiving FFNS had significantly greater improvements from baseline in reflective total ocular symptom scores (TOSS) than those receiving placebo (LS mean difference -0.546; p = 0.008). Significant improvements in ocular symptoms with FFNS versus placebo were also observed for morning pre-dose instantaneous TOSS (LS mean difference -0.519; p = 0.009). FFNS had a favorable safety and tolerability profile: fewer adverse events occurred with FFNS (22%) than with placebo (29%), and no serious adverse events were observed.. FFNS 110 microg once daily demonstrated efficacy in relieving both the nasal and ocular symptoms of SAR in adult and adolescent patients.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Cedrus; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Eye Diseases; Female; Humans; Male; Middle Aged; Nose Diseases; Placebos; Pollen; Rhinitis, Allergic, Seasonal; Treatment Outcome; Young Adult

Eye symptoms frequently occur in patients with allergic rhinitis and are among the most bothersome symptoms. Intranasal steroids have been shown to reduce ocular symptoms associated with allergic nasal symptoms, even though they do not reach the eye.. To elucidate a mechanism to explain these observations.. We performed a double-blind, placebo-controlled, crossover experiment in 20 subjects with seasonal allergic rhinitis. Nasal antigen challenge was performed consecutively for 3 days after 1 week of treatment with either placebo or fluticasone furoate nasal spray (FFNS). Subjects recorded their nasal and ocular symptoms, and nasal secretions were quantified. Nasal scrapings to quantify eosinophils were obtained before each antigen challenge.. Nasal challenge with antigen led to sneezing, a nasonasal, and a nasal-ocular reflex. Priming in the number of sneezes, contralateral nasal secretion weights, and total eye symptoms were observed. Treatment with FFNS reduced sneezing, the nasonasal and nasal-ocular reflexes, and the amount of eosinophils in nasal secretions.. We confirmed that a nasal-ocular reflex follows nasal challenge with allergen and that it can contribute to the ocular symptoms associated with allergic rhinitis. FFNS reduced eosinophil infiltration, priming, and ocular symptoms. Furthermore, our results support a mechanism by which control of eye symptoms can be achieved during nasal administration of an intranasal steroid in patients with seasonal allergic rhinitis.

Topics: Administration, Intranasal; Adult; Allergens; Androstadienes; Anti-Allergic Agents; Cross-Over Studies; Double-Blind Method; Eosinophils; Eye; Female; Humans; Male; Nasal Provocation Tests; Nose; Reflex, Abnormal; Rhinitis, Allergic, Seasonal

Burdensome symptoms of allergic rhinitis (AR) include nasal and ocular symptoms such as itching, tearing and redness. Intranasal corticosteroids are efficacious in the treatment of nasal symptoms of AR.. It was the aim of this study to determine the efficacy of the intranasal corticosteroid mometasone furoate nasal spray (MFNS) in relieving ocular symptoms associated with seasonal AR (SAR).. Ocular symptom data were analyzed for subjects >or=12 years of age, randomized to MFNS 200 mug q.d. (n = 176) or placebo (n = 177) in a placebo-controlled, double-blind clinical trial. Post hoc efficacy analysis assessed the mean change from baseline in subject-reported total ocular symptom scores (TOSS) averaged over the treatment period.. Mean baseline TOSS was 4.91 for the MFNS group and comparable (5.05) for the placebo group - combined average for individual symptoms such as itching, tearing and redness ranged from 0 (no symptoms) to 9 (all symptoms, severe). Mean change from baseline in TOSS averaged over days 1-15 was -1.42 for the MFNS group and -0.94 for the placebo group (p = 0.02), for an observed treatment difference of 0.49 (statistical data rounded to 2 decimal positions). Improvement in individual symptoms (eye itching, tearing and redness) contributed to this treatment effect; the greatest improvement occurred with tearing, which decreased -0.52 from the baseline score 1.59 in the MFNS group and -0.31 from 1.67 in those receiving placebo (p < 0.01), for an observed treatment difference of 0.21. Treatment with MFNS was safe and well tolerated.. MFNS is effective in reducing ocular symptoms of SAR, in addition to its established efficacy in reducing nasal symptoms of SAR.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Budesonide; Child; Double-Blind Method; Eye Diseases; Female; Humans; Male; Middle Aged; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Seasonal

This study was designed to evaluate the efficacy and safety of fluticasone furoate nasal spray (FFNS), a novel enhanced-affinity intranasal corticosteroid, in Japanese patients with perennial allergic rhinitis (PAR), and to determine the optimal dose.. In this phase II, multicenter, double-blind, randomized, placebo-controlled, parallel-group, dose-ranging study, 240 patients (aged >or= 16 years) received once-daily (od) treatment for 2 weeks with either FFNS 110 microg (n = 80), 220 microg (n = 81) or placebo (n = 79). Patients evaluated 3 nasal symptoms using a 4-point scale. Efficacy was assessed as the mean change from baseline in total nasal symptom score (TNSS).. Treatment with FFNS resulted in a significantly greater decrease over the treatment period in the mean 3TNSS (sneezing, rhinorrhea, and nasal congestion; p < 0.001 each dose vs. placebo), compared with placebo. More patients receiving FFNS had a markedly or moderately improved impression of treatment than placebo recipients (48% and 49% for FFNS 110 micro and 220 microg, respectively, vs. 18% for placebo; p < 0.001). Nasal rhinoscopy findings revealed significant improvements in mucosal swelling of the inferior turbinate (110 microg: p = 0.004; 220 micro: p = 0.011) and amount of watery rhinorrhea (110 microg: p = 0.003; 220 microg: p < 0.001), compared with placebo. Both doses of FFNS were well tolerated.. Both FFNS 110 microg and 220 microg od were effective in alleviating nasal symptoms in Japanese patients with PAR over the 2-week duration of this study. FFNS 110 microg od was selected as the optimal dose for further evaluation in phase III clinical trials.

Topics: Administration, Intranasal; Adult; Aged; Androstadienes; Asian People; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Nasal Mucosa; Rhinitis, Allergic, Seasonal; Time Factors

Product attributes influence patient preference for intranasal corticosteroid therapy in allergic rhinitis (AR).. The aim of the study was to compare the product sensory attributes and patient preferences of fluticasone furoate (FF) and fluticasone propionate (FP) nasal sprays in patients with symptomatic perennial and/or seasonal AR.. This randomized, multicenter, double-blind, single-dose, crossover study enrolled 127 patients with a diagnosis of AR as determined by respiratory symptoms and a positive skin test to perennial and/or seasonal allergens within 12 months prior to the study. Patients could not use FF or FP within 4 weeks prior to the start of the study. Patients were randomized 1:1 to receive FF (110 microg) followed by FP (200 microg) or FP followed by FF. A 10-minute washout period occurred before crossover dosing. Following each treatment, patient-rated sensory attributes were assessed immediately and 2 minutes after treatment on 2 questionnaires using a 7-point Likert scale (scored from 0-6) rating odor, taste, aftertaste, drip down the throat, urge to sneeze, soothing feeling, irritation, and nose runoff. At the end of the crossover dosing and after completion of the attributes questionnaires, preference for individual attributes of FF or FP nasal spray and overall patient preference were evaluated in a third questionnaire that asked "Based on these attributes, which product did you prefer overall?" Additionally, a follow-up phone call was conducted 24 hours after the study to assess any adverse events following study treatment.. Patients (mean age, 39.7 years; 80% white; 65% women) preferred FF nasal spray over FP nasal spray overall (60% vs 33%; P = 0.003) and based on the individual attributes of odor (64% vs 29%; P < 0.001), taste (47% vs 21%; P < 0.001), aftertaste (44% vs 22%; P = 0.002), drip down the throat (43% vs 27%; P = 0.037), and nose runoff (49% vs 19%; P < 0.001). Patient ratings favored FF versus FP (median differences, P < 0.001) with respect to odor, taste, dripping down the throat, and nose runoff, both immediately and 2 minutes after dosing, but there were no significant differences with respect to whether the medication felt soothing, caused nasal irritation, or made patients sneeze. Fifty-two percent (63/121) of patients replied that they were very likely to comply with FF treatment versus FP treatment (38% [45/120]; P = 0.02) if the medications were prescribed. Three patients (2%) reported adverse events (dizziness, headache, nasal congestion) during treatment with FF.. In this study of adult AR patients, the sensory attributes of FF were preferred over those of FP following single-dose administration.

Topics: Administration, Intranasal; Adult; Aerosols; Androstadienes; Anti-Allergic Agents; Cross-Over Studies; Double-Blind Method; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Mucosa; Odorants; Patient Satisfaction; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sensation; Sensory Thresholds; Surveys and Questionnaires; Taste; Treatment Outcome; United States

The Vienna Challenge Chamber (VCC) offers a controlled and controllable paradigm in which to reproducibly evaluate the efficacy of anti-allergic treatment. The aim of this study was to assess the efficacy of the novel intranasal corticosteroid fluticasone furoate (FF) in the VCC.. The single-centre, randomised, double-blind, placebo-controlled, two-period crossover study was conducted in 59 adult males with grass pollen allergic rhinitis (AR). Patients received either Fluticasone furoate 200 mcg once-daily, or placebo intranasally for 8 days. AR symptoms were induced during 4-hour allergen challenges with grass pollen in the VCC at the end of each 8-day treatment period. A first challenge was conducted at 1-5 hours post-dose, followed by a second challenge at 22-26 hours post-dose. The primary endpoint was total nasal symptom score (TNSS; sum of itch, sneeze, rhinorrhoea, obstruction symptoms assessed on a categorical scale of 0-3) weighted mean over 2-5 hours post-dose. Secondary endpoints included: TNSS weighted mean over 23-26 hours post-dose and global symptom score, eye symptom score, nasal secretions and nasal airflow weighted means over 2-5 and 23-26 hours post-dose.. Fluticasone furoate showed consistent attenuation of AR symptoms in both the early and late challenges. Compared with placebo, weighted mean of TNSS was reduced on average by 4.14 point-scores at 2-5 hours post-dose and 3.63 point scores at 23-26 hours post-dose. These positive effects were also seen across all secondary endpoints.. An 8-day treatment course of intranasal FF 200 mcg given once-daily statistically significantly reduced symptoms of AR including associated eye symptoms. Statistical significance was declared where the relevant two-sided 95% confidence interval did not contain zero. This positive effect was sustained over 24 hours suggesting that fluticasone furoate could be efficacious as a once daily steroid.

Topics: Adolescent; Adult; Androstadienes; Cross-Over Studies; Double-Blind Method; Environmental Exposure; Glucocorticoids; Humans; Male; Middle Aged; Poaceae; Rhinitis, Allergic, Seasonal; Treatment Outcome

It is essential to assess potential growth effects of any newly developed corticosteroid. Fluticasone furoate is a recently approved, enhanced- affinity intranasal corticosteroid with low systemic bioavailability and proven efficacy in treating allergic rhinitis.. The aim of the current study was to assess whether treatment with fluticasone furoate nasal spray affected the short-term lower-leg growth rate in children with allergic rhinitis.. Prepubertal children with seasonal or perennial allergic rhinitis of at least 1 year's duration were included in this single-center, randomized, double-blind, placebo-controlled, crossover study. The study consisted of 4 periods, each of 2 weeks' duration screening, then 2 treatment periods separated by a washout). Study medications were fluticasone furoate nasal spray 110 microg and placebo nasal spray, both administered QD in the morning. The primary end point, lower-leg growth rate (measured in millimeters per week), was assessed by knemometry. Adverse events were also assessed.. Fifty-eight patients were randomized to the study and comprised the intent-to-treat (ITT) population (mean [SD] age, 9.1 [1.4] years; 39 males, 19 females). Five patients were excluded from the ITT group due to protocol violations; thus, 53 patients (mean [SD] age, 9.0 [1.4] years; 35 males, 18 females) comprised the growth population (a de facto per-protocol group). In the growth population, the adjusted mean lower-leg growth rate was 0.40 and 0.42 mm/wk with fluticasone furoate and placebo, respectively. The difference in adjusted mean lower-leg growth rate between fluticasone furoate and placebo was -0.016 mm/wk (95% CI, -0.13 to 0.10). Fluticasone furoate was noninferior to placebo, as the lower boundary of the 95% CI was above the prespecified noninferiority margin of -0.20 mm/wk. These results were supported by the ITT analysis. Fluticasone furoate nasal spray was well tolerated and had an adverse-event profile similar to that of placebo nasal spray. Nasopharyngitis (placebo, 4; fluticasone furoate, 1) and headache (placebo, 3; fluticasone furoate, 1) were the most frequent adverse events during the treatment periods.. In this study, fluticasone furoate nasal spray 110 microg QD for 2 weeks had no effect on lower-leg growth rate in these prepubertal children with allergic rhinitis.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Aerosols; Androstadienes; Child; Cross-Over Studies; Double-Blind Method; Female; Growth and Development; Growth Disorders; Humans; Lower Extremity; Male; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Time Factors; Treatment Outcome

Topics: Administration, Intranasal; Aerosols; Androstadienes; Glucocorticoids; Humans; Nonprescription Drugs; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Treatment Outcome

Various minimal clinically important difference (MCID) threshold estimation techniques have been applied to seasonal allergic rhinitis (SAR). The objectives of this study are to (i) assess the difference in magnitude of alternative SAR MCID threshold estimates and (ii) evaluate the impact of alternative MCID estimates on health technology assessment (HTA).. Data describing change from baseline of the reflective Total Nasal Symptom Score (rTNSS) for four intranasal SAR treatments were obtained from United States Food and Drug Administration-approved prescribing information. Treatment effects were then compared with anchor-based MCID thresholds derived by Barnes et al. and thresholds obtained from an Agency for Healthcare Research and Quality (AHRQ) panel.. The change in rTNSS score from baseline, represented as the average of the twice-daily recorded scores of the rTNSS, was -2.1 (p < .001) for azelastine hydrochloride 0.10%, 1.35 (p = .014) for ciclesonide, and -1.47 (p < .001) for fluticasone furoate. The change in the rTNSS score from baseline, represented by sum of the AM and PM score, was -2.7 for MP-AzeFlu (p < .001). The rTNSS change from baseline for each product was compared with anchor-based MCID threshold and the AHRQ panel estimates. Comparison of the observed treatment effect to the anchor-based and AHRQ panel MCID thresholds results in different conclusions, with clinically important differences being inferred when anchor-based estimates serve as the reference point.. The AHRQ panel MCID threshold for the rTNSS was twelve times larger than the anchor-based estimates resulting in conflicting recommendations on whether different SAR treatments provide clinically meaningful benefit.

Topics: Androstadienes; Anti-Allergic Agents; Humans; Minimal Clinically Important Difference; Phthalazines; Pregnenediones; Rhinitis, Allergic, Seasonal; Technology Assessment, Biomedical

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Conjunctivitis, Allergic; Humans; Nasal Sprays; Rhinitis, Allergic, Seasonal

Fluticasone furoate is a novel glucocorticoid receptor agonist marketed as a treatment for seasonal and perennial allergic rhinitis. Forced degradation of fluticasone furoate under conditions of light led to a number of degradation products, the structures of which were elucidated using mass spectrometry and a range of one and two-dimensional NMR experiments. Three structures were derived, including two which involved a rearrangement of the steroid ring A to give cross-linked degradation products. The results demonstrate the applicability of a previously observed mechanism of photodegradation to fluticasone furoate.

Topics: Androstadienes; Anti-Allergic Agents; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Molecular; Molecular Structure; Photolysis; Receptors, Glucocorticoid; Rhinitis; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Androstadienes; Conjunctivitis, Allergic; Controlled Clinical Trials as Topic; Evidence-Based Medicine; Humans; Rhinitis, Allergic, Seasonal; Triamcinolone Acetonide

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Child; Child, Preschool; Drug Administration Schedule; Drug Interactions; Humans; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome