Phenylephrine hydrochloride modified-release tablets for nasal congestion: a randomized, placebo-controlled trial in allergic rhinitis patients.

BACKGROUND: Over-the-counter phenylephrine hydrochloride (PEH) is used for relief of nasal congestion caused by allergic rhinitis; however, data to support its efficacy are lacking. The US Food and Drug Administration recommended clinical trials to evaluate the efficacy and safety of PEH in patients with this condition. OBJECTIVE: To evaluate the efficacy and safety of PEH 30-mg modified-release (MR) tablets in patients with nasal congestion caused by allergic rhinitis in a multicenter, randomized, double-blinded, placebo-controlled, 2-arm, parallel-group study. METHODS: Eligible adults at least 18 years old with documented hypersensitivity to fall pollen allergens were randomized to PEH-MR or placebo every 12 hours for 7 days from August 30 to October 12, 2011. The primary end point was mean change from baseline during the entire treatment period in daily reflective nasal congestion score. Secondary end points included changes in other symptom score assessments, time to maximal effect, duration of effect, and quality of life. Safety assessments included adverse events, serious adverse events, vital signs, physical examination, and electrocardiograms. RESULTS: Of 575 patients, 288 received PEH-MR and 287 received placebo. No significant beneficial difference was detected between PEH-MR and placebo for the primary end point (PEH-MR, mean -0.394, SD 0.4880; placebo, mean -0.412, SD 0.5383; P = .2655). Likewise, no significant differences were observed for most secondary end points or quality of life. Overall, 89 of 575 patients (15.5%), equally distributed between the PEH-MR and placebo groups, experienced at least 1 treatment-emergency adverse event. CONCLUSION: PEH-MR 30-mg tablets taken orally every 12 hours for 7 days is not more efficacious than placebo in relieving nasal congestion caused by allergic rhinitis. TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT01413958, protocol CL2011-06.

The mountain cedar model in clinical trials of seasonal allergic rhinoconjunctivitis.

BACKGROUND: Clinical trials of seasonal allergic rhinoconjunctivitis use the mountain cedar (Juniperus ashei) season as the predominate model. OBJECTIVE: To evaluate clinical trials of rhinoconjunctivitis using mountain cedar, to present analysis of pollen counts during 18 seasons, and to discuss the model. METHODS: The medical literature was searched for clinical trials performed using mountain cedar either in or out of season. Pollen counts were recorded and analyzed for the duration of 18 seasons. RESULTS: Thirty-eight trials were identified. Of these, 1 evaluated onset of allergy, 8 were immunotherapy trials, 28 were pharmaceutical clinical trials, and 1 studied symptoms elicited in a pollen challenge chamber trial. Many generic equivalency trials are unreported. In the 18 years of counts in the Texas Hill Country, a dependable and intense pollen density was present in every season. The combination of dependable seasons without confounding pollens, the large number of allergic patients, and the ability to concentrate resources in one geographic area has made mountain cedar allergy a mainstay for therapeutic trials for allergic rhinoconjunctivitis. CONCLUSION: Mountain cedar allergy presents a dependable and durable model of allergic rhinoconjunctivitis.

Efficacy of bepotastine besilate ophthalmic solution 1.5% for seasonal allergic conjunctivitis: a randomized, placebo-controlled, natural exposure, clinical trial.

Allergic conjunctivitis (AC) affects an estimated 20% of the population in the Western world, with a large fraction suffering due to seasonal or perennial allergen exposures. Bepotastine besilate ophthalmic solution (BBOS) 1.5%, a dual-acting histamine (H(1)) receptor antagonist and mast cell stabilizer, is indicated for itching associated with AC. This study was designed to evaluate the efficacy and safety of BBOS 1.5% for reducing ocular itching associated with AC in subjects enrolled in a natural exposure trial. Eligible subjects in a multicenter, double-masked, randomized, parallel-group, placebo-controlled, natural exposure clinical trial were randomly assigned to either BBOS 1.5% or placebo eyedrops on a 1:1 basis and instilled 1 drop of the test agent into both eyes twice daily for 2 weeks. The mean change from baseline in instantaneous and reflective ocular itching scores at the end of 2 weeks of treatment were evaluated based on subject-assessed severity of instantaneous and reflective itching. Subject-reported adverse events (AEs) were also recorded for safety. Treatment with BBOS 1.5% significantly reduced instantaneous and reflective ocular itching scores from baseline compared with placebo over the 2-week study period(p = 0.007 and p = 0.005, respectively). BBOS 1.5% was well tolerated, and AEs were generally transient and mild. This clinical study indicates BBOS 1.5% effectively and safely treated ocular itching in a natural exposure allergy study and is a useful treatment option for the management of ocular itching associated with AC. (ClinicalTrials.gov identifier number: NCT01174823.)

Once-daily treatment with beclomethasone dipropionate nasal aerosol does not affect hypothalamic-pituitary-adrenal axis function.

BACKGROUND: Intranasal corticosteroids are effective in controlling allergic rhinitis (AR) symptoms; however, chronic administration of corticosteroids may suppress hypothalamic-pituitary-adrenal (HPA)-axis function. OBJECTIVE: To evaluate the effects of 6 weeks of treatment with beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol on HPA-axis function in subjects with perennial AR (PAR). METHODS: In this randomized, double-blind, placebo- and active-controlled study, subjects aged 12 to 45 years were randomized to receive BDP nasal aerosol 320 µg/day (n = 50), placebo (n = 46), or placebo/prednisone (prednisone 10 mg/day for the last 7 days of the treatment period [n = 11]). The primary end point was change from baseline in 24-hour serum cortisol (SC) weighted mean (expressed as geometric mean ratio [GMR]) in the BDP and placebo group after 6 weeks of treatment. RESULTS: Geometric SC-weighted mean values were similar in the BDP and placebo groups at baseline (9.04 and 8.45 µg/dL, respectively) and after 6 weeks (8.18 and 8.01 µg/dL, respectively). After 6 weeks of treatment, BDP was noninferior to placebo with respect to the ratio from baseline in SC-weighted mean (GMR: 0.96 [95% CI: 0.87, 1.06]). In contrast, 7 days of prednisone treatment substantially reduced geometric SC-weighted mean values from baseline (approximate 3-fold reduction [from 7.33 to 2.31 µg/dL]) compared with placebo. BDP nasal aerosol was well tolerated, and the safety profile was similar to that of placebo. CONCLUSION: Treatment with BDP nasal aerosol, 320 µg once daily, was not associated with HPA-axis suppression in adolescent and adult subjects with PAR. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01133626.

A study of the efficacy and safety of ciclesonide hydrofluoroalkane nasal aerosol in patients with seasonal allergic rhinitis from mountain cedar pollen.

A nasal aerosol formulation of ciclesonide with a hydrofluoroalkane propellant (CIC-HFA) is currently in development for treatment of allergic rhinitis (AR). This study evaluated the efficacy and safety of once-daily administration of CIC-HFA 74 or 148 micrograms compared with placebo in patients with seasonal AR (SAR) from mountain cedar pollen. Patients ≥12 years of age with a ≥2-year history of SAR from mountain cedar pollen were randomized in a placebo-controlled, double-blind, parallel group, multicenter study to CIC-HFA 74 micrograms, CIC-HFA 148 micrograms, or placebo once daily in the morning for 2 weeks. Change from baseline in reflective total nasal symptom score (rTNSS), instantaneous TNSS (iTNSS), and reflective total ocular symptom score (rTOSS) in patients with baseline rTOSS ≥5.00 were evaluated. Adverse events (AEs) were monitored throughout the study. A statistically significant improvement in rTNSS (least squares [LS] mean change from baseline 1.04 and 1.02 respectively; p < 0.0001 versus placebo for both) and iTNSS (LS mean change from baseline 0.90 and 0.83 respectively; p < 0.001 vs placebo for both) was observed after treatment with CIC-HFA 74- or 148-microgram doses. Only the CIC-HFA 74-micrograms treatment group showed a statistically significant improvement in rTOSS (LS mean change from baseline 0.52; p = 0.0124) compared with placebo. The overall incidence of AEs was low and comparable between the treatment groups. In this study, statistically significant improvements in nasal symptoms of SAR were observed after treatment with CIC-HFA 74-microgram or CIC-HFA 148-microgram doses. Both active treatments were well tolerated. Clinical trial registry URL and registration number: www.clinicaltrials.gov/ct2/show/NCT01010971.

Efficacy and safety of once-daily treatment with beclomethasone dipropionate nasal aerosol in subjects with seasonal allergic rhinitis.

An aerosol formulation may be preferred by some allergic rhinitis (AR) patients, to avoid the "wet feeling" and nasal runoff associated with aqueous nasal corticosteroid sprays. Beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol is a recently developed, nonaqueous, nonchlorofluorocarbon formulation of BDP for the treatment of AR. This study was designed to evaluate the efficacy, safety, and quality-of-life benefits of BDP nasal aerosol in subjects with seasonal AR (SAR). Eligible subjects (≥12 years of age) enrolled in this 2-week study were randomized to either BDP nasal aerosol at 320 µg/day (n = 169) or placebo (n = 171). Efficacy assessments included reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS, respectively), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, reflective and instantaneous total ocular symptom scores (rTOSS and iTOSS, respectively), and physician-assessed total nasal symptom score (PNSS). Safety and tolerability were also assessed. Subjects receiving BDP nasal aerosol showed a significantly greater improvement from baseline in average A.M. and P.M. rTNSS versus placebo (treatment difference, -0.91; 95% confidence interval, -1.3, -0.5; p < 0.001) over 2 weeks of treatment. Greater improvements in rTNSS with BDP nasal aerosol compared with placebo were evident by day 2 and were maintained throughout the treatment period. Similarly, significant improvements were seen with BDP nasal aerosol in iTNSS (p < 0.001) and RQLQ score (p = 0.005) compared with placebo. Treatment with BDP nasal aerosol also resulted in greater improvements in rTOSS (p = 0.002), iTOSS (p = 0.003), and PNSS (p < 0.001) relative to placebo. BDP nasal aerosol was well tolerated and the overall safety profile was similar to placebo. Results from this clinical study indicated that BDP nasal aerosol provided significant AR symptom relief and was well tolerated in patients with SAR with an overall safety profile similar to placebo. Clinicaltrials.gov identifier: NCT01024608.

The efficacy of intranasal antihistamines in the treatment of allergic rhinitis.

OBJECTIVES: To discuss the new use of intranasal antihistamines as first-line therapies, compare and contrast this class of medication with the traditionally available medications, and discuss the potential for intranasal antihistamines to provide relief superior to second-generation oral antihistamines. DATA SOURCES: Review articles and original research articles were retrieved from MEDLINE, OVID, PubMed (1950 to November 2009), personal files of articles, and bibliographies of located articles that addressed the topic of interest. STUDY SELECTION: Articles were selected for their relevance to intranasal antihistamines and their role in allergic rhinitis. Publications included reviews, treatment guidelines, and clinical studies (primarily randomized controlled trials) of both children and adults. RESULTS: This panel was charged with reviewing the place of intranasal antihistamines in the spectrum of treatment for allergic rhinitis. Intranasal antihistamines have been shown in numerous randomized, placebo-controlled trials to be more efficacious than the oral antihistamines. Although intranasal corticosteroids are considered by some to be superior to intranasal antihistamines, multiple studies have shown an equal effect of the 2 classes of medication. Both intranasal corticosteroids and intranasal antihistamines have been shown to reduce all symptoms of allergic rhinitis. In addition, some intranasal antihistamines have a more rapid onset of action than intranasal corticosteroids. CONCLUSIONS: The future of allergy treatment will likely involve a combination of both intranasal corticosteroids and intranasal antihistamines because of the benefits of local administration and their additive effect on efficacy.

Safety and efficacy of olopatadine hydrochloride nasal spray 0.6% in pediatric subjects with allergic rhinitis.

Olopatadine (OLO) nasal spray 0.6% is indicated for treatment of seasonal allergic rhinitis (SAR) in subjects > or = 12 years of age. This study was designed to present the results of two studies that evaluated the efficacy, safety, and pharmacokinetics (PK) of OLO in children with allergic rhinitis (AR). These were multicenter, double-blind, randomized, parallel-group studies in subjects 6 to <12 years of age (study 1) and 2 to <6 years of age (study 2) with SAR (study 1) or AR (study 2). In study 1, nasal and ocular symptoms were scored for efficacy, and study 2 included PK analyses. In both studies, subjects were evaluated based on physical/nasal examinations and adverse events (AEs). Overall, 1188 subjects (study 1) and 132 subjects (study 2) were randomized, respectively. OLO (1 or 2 sprays/nostril, b.i.d.) was superior to vehicle in the percent decrease in reflective total nasal symptom scores (p < or = 0.0120). OLO 1 spray/nostril b.i.d. was also superior to vehicle in the percent decreases in reflective total ocular symptom scores (p < or = 0.0084), change from baseline in Pediatric Rhinoconjunctivitis Quality-of-Life Questionnaire scores (p < or = 0.0377), Caregiver Treatment Satisfaction Questionnaire scores (p < or = 0.0450), and proportions of subjects reporting improvements in Subject Global Assessments (p = 0.0035). The most frequently reported treatment-related events in the OLO group were bad/bitter taste and epistaxis. In subjects 6 to <12 years of age, OLO was superior to vehicle in the treatment of SAR. In subjects 2 to <12 years of age, OLO had an overall low rate of AEs and low systemic exposure.

Intranasal corticosteroids in the treatment of allergic rhinitis.

Intranasal corticosteroids (INCSs) have been established as the first-line treatment of moderate to severe allergic rhinitis (AR). Compared with other monotherapies, INCSs are most effective at controlling underlying allergic inflammation and providing symptom relief. Although currently available INCSs show comparable efficacy in controlling nasal symptoms of AR, onset and duration of action are thought to be somewhat variable among the INCSs. The low frequency of side effects suggests that, at recommended doses, INCSs are safe for the treatment of AR. However, concerns remain regarding the long-term systemic side effects associated with INCS therapy. Recent clinical studies have indicated that ciclesonide provides effective relief from nasal symptoms of AR and may have a rapid onset of action. Moreover, the results of two clinical trials, including a 52-week study, have suggested that intranasal ciclesonide does not cause cortisol suppression. Furthermore, intranasal ciclesonide does not have an additive effect on the hypothalamic-pituitary-adrenal-axis function when administered in combination with inhaled corticosteroids (ICSs), indicating that intranasal ciclesonide can be used in combination with an ICS in patients with asthma and comorbid AR. Therefore, intranasal ciclesonide appears to provide an additional treatment option for patients with AR.

Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective.

OBJECTIVE: To evaluate the cost of lost productivity in the workplace due to allergic rhinitis compared to other selected medical conditions from an employer perspective. SETTING AND PARTICIPANTS: A total of 8267 US employees at 47 employer locations who volunteered to participate in health/wellness screenings. MEASUREMENTS: The Work Productivity Short Inventory was used to assess the impact of a predefined group of health conditions on workplace productivity for the previous 12 months. Both absenteeism and presenteeism (lost productivity while at work) were recorded. Costs were calculated using a standard hourly wage. RESULTS: Allergic rhinitis was the most prevalent of the selected conditions; 55% of employees reported experiencing allergic rhinitis symptoms for an average of 52.5 days, were absent 3.6 days per year due to the condition, and were unproductive 2.3 h per workday when experiencing symptoms. The mean total productivity (absenteeism + presenteeism) losses per employee per year were 593 US dollars for allergic rhinitis, 518 US dollars for high stress, 277 US dollars for migraine, 273 US dollars for depression, 269 US dollars for arthritis/rheumatism, 248 US dollars for anxiety disorder, 181 US dollars for respiratory infections, 105 US dollars for hypertension or high blood pressure, 95 US dollars for diabetes, 85 US dollars for asthma, and 40 US dollars for coronary heart disease. The mean total productivity loss per employee per year due to caregiving was 102 US dollars for pediatric respiratory infections, 85 US dollars for pediatric allergies, 49 US dollars for Alzheimer's disease, and 42 US dollars for otitis media/earache. CONCLUSIONS: Allergies are major contributors to the total cost of health-related absenteeism and presenteeism. Payers and employers need to consider this when determining health benefits for employees.

Oral Phenylephrine HCl for Nasal Congestion in Seasonal Allergic Rhinitis: A Randomized, Open-label, Placebo-controlled Study.

BACKGROUND: Phenylephrine hydrochloride (PE HCl) is widely used for the treatment of nasal congestion, but efficacy at the 10-mg dose is not known for certain. The Food and Drug Administration has requested that sufficiently powered, multicenter, dose-ranging studies be conducted to assess the efficacy and safety of PE HCl. OBJECTIVE: To evaluate subjective nasal congestion symptom relief and safety of 4 different doses of PE HCl immediate-release 10-mg tablets and placebo in adults with seasonal allergic rhinitis (SAR). METHODS: This multicenter, phase 2, parallel, open-label trial randomized 539 adults with SAR (but otherwise healthy) to 7 days of treatment with either PE HCl 10-mg tablets at fixed doses of 10, 20, 30, or 40 mg or placebo. The primary efficacy end point was the mean change from baseline over the entire treatment period in daily reflective nasal congestion score. Other efficacy end points and safety were also evaluated. RESULTS: None of the PE HCl treatment groups had a statistically significant change from baseline in instantaneous or reflective nasal congestion scores compared with the placebo group. PE HCl was well tolerated at doses of up to 30 mg. At least 1 treatment-emergent adverse event was experienced by 18.4% of the participants, the most common being headache (3.0%). CONCLUSIONS: PE HCl, at doses of up to 40 mg every 4 hours, is not significantly better than placebo at relieving nasal congestion in adults with SAR. The phenylephrine section of the Food and Drug Administration monograph on over-the-counter cold, cough, allergy, bronchodilator, and antiasthmatic products should be revised accordingly.

Use of intranasal cromolyn sodium for allergic rhinitis.

Allergic rhinitis affects 10% to 20% of Americans. It frequently coexists with other conditions, such as allergic conjunctivitis, sinusitis, and asthma, and is associated with impaired occupational function and performance in school, decreased quality of life, and increased health care costs. An efficacious agent with minimal adverse effects and a lack of drug interactions is needed to help simplify treatment of allergic rhinitis, especially in patients with comorbidities. Controlled studies of intranasal cromolyn sodium therapy for patients with seasonal and perennial allergic rhinitis are reviewed, and appropriate candidates for treatment with this agent are discussed. Cromolyn inhibits the degranulation of sensitized mast cells, thereby blocking the release of inflammatory and allergic mediators. It reduces symptoms of allergic rhinitis, and, when used prophylactically, cromolyn can prevent symptoms from occurring. Controlled studies comparing cromolyn with placebo, intranasal corticosteroids, and antihistamines have shown the efficacy of cromolyn in relieving rhinitis symptoms. In addition, because cromolyn is poorly absorbed systemically, it is well tolerated and not associated with drug interactions. Intranasal cromolyn has an excellent safety record, is available as an over-the-counter medication, and has been proved to be efficacious in patients with allergic rhinitis.

Pharmacokinetic profile of beclomethasone dipropionate hydrofluoroalkane after intranasal administration versus oral inhalation in healthy subjects: results of a single-dose, randomized, open-label, 3-period crossover study.

BACKGROUND: Beclomethasone dipropionate (BDP) is an anti-inflammatory corticosteroid that is rapidly metabolized to the pharmacologically active monoester, beclomethasone-17-monopropionate (17-BMP). Recently, a hydrofluoroalkane (HFA)-propelled nasal aerosol formulation of BDP was developed to treat allergic rhinitis. However, the pharmacokinetic profile of BDP HFA nasal aerosol has not been previously investigated. OBJECTIVE: This study evaluated and compared the systemic levels of 17-BMP and BDP after a single dose of intranasally administered or orally inhaled BDP HFA in healthy subjects. METHODS: In this single-center, randomized, open-label, 3-period crossover study, healthy subjects received single doses of intranasal BDP HFA (80 and 320 µg) and orally inhaled BDP HFA (320 µg). The primary pharmacokinetic parameters assessed were area under the concentration-time curve until the last measurable value (AUC(last)) and C(max) for 17-BMP. For AUC(last) and C(max), point estimates for treatment differences and CIs were calculated on the log scale and then exponentiated to provide estimates of the geometric mean ratios (GMRs) and associated CIs. RESULTS: Thirty subjects were randomized to receive study medication (aged 18-45 years, 66.7% male). Mean plasma concentrations of 17-BMP after intranasal administration of BDP HFA (for both 80- and 320-µg doses) were substantially lower than that of orally inhaled BDP HFA (320 µg) across all time points. Mean AUC(last) values of 17-BMP for intranasal 80 µg, intranasal 320 µg, and orally inhaled 320 µg were 295.8, 1139.7, and 4140.3 pg·hr/mL, respectively. Mean C(max) values were 92.1, 262.7, and 1343.7 pg/mL, respectively. The GMR of AUC(last) for 17-BMP with intranasal BDP HFA 320 µg versus orally inhaled BDP HFA 320 µg was 0.275, indicating substantially lower systemic bioavailability with intranasal administration than with oral inhalation. Similarly, the GMR of AUC(last) for 17-BMP with intranasal BDP HFA 80 µg versus 320 µg was 0.260, suggesting approximate dose proportionality (4-fold difference). Pharmacokinetic results for BDP were similar to those seen for 17-BMP. All doses of intranasal and orally inhaled BDP HFA were well tolerated, and no treatment-related adverse events were reported. CONCLUSIONS: The results of this study suggest that 80 and 320 µg BDP HFA nasal aerosols have substantially lower systemic bioavailability than 320 µg orally inhaled BDP HFA in healthy subjects. All treatments were well tolerated. ClinicalTrials.gov identifier: NCT01537692.

Double-blind, placebo-controlled study of azelastine and fluticasone in a single nasal spray delivery device.

BACKGROUND: A proof-of-concept study suggested that combination therapy with commercial azelastine hydrochloride nasal spray and fluticasone propionate nasal spray significantly improved nasal symptoms of seasonal allergic rhinitis compared with either agent alone. OBJECTIVE: To compare an azelastine-fluticasone combination nasal spray administered in a single-delivery device with a commercially available azelastine nasal spray and fluticasone nasal spray. METHODS: This 14-day, multicenter, randomized, double-blind study was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in, 610 patients with moderate-to-severe nasal symptoms were randomized to treatment with (1) azelastine nasal spray, (2) fluticasone nasal spray, (3) combination azelastine and fluticasone nasal spray, or (4) placebo nasal spray. All treatments were given as 1 spray per nostril twice daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of nasal congestion, runny nose, itchy nose, and sneezing. RESULTS: All 3 active groups were statistically superior (P

Mometasone furoate nasal spray is safe and effective for 1-year treatment of children with perennial allergic rhinitis.

OBJECTIVE: Perennial allergic rhinitis (PAR) affects children at a young age. Current guidelines recommend intranasal corticosteroids as the first-line treatment in patients with moderate-to-severe or persistent disease or in those who have congestion. In this study, the long-term safety and efficacy of mometasone furoate nasal spray (MFNS) were assessed in children with PAR. METHODS: In this multicenter, active-controlled, evaluator-blind, 12-month study, 255 children aged 6-11 years with a >or=1-year history of PAR were randomized to receive once-daily MFNS 100 microg (n=166) or the active comparator beclomethasone dipropionate (BDP) 168 microg (n=85). Changes from baseline in overall PAR symptoms and response to treatment were rated at each visit. Cosyntropin stimulation testing, as well as tonometry and slit lamp procedures, were performed. Safety variables were assessed. RESULTS: A total of 137 subjects in the MFNS group and 68 in the BDP group completed treatment. The mean reductions in physician- and subject-rated overall condition of PAR at week 52 were -42.1% and -39.7%, respectively, for MFNS, compared with -44.0% and -39.0%, respectively, for BDP. A total of 94% and 100% of MFNS and BDP subjects, respectively, reported adverse events (AEs), which were mostly mild or moderate. The most frequently reported treatment-related AEs in both groups were epistaxis, headache, and pharyngitis. Response to cosyntropin was normal and no posterior subcapsular cataracts were observed in either group. Although no significant changes in intraocular pressure were observed with MFNS, one subject receiving BDP demonstrated this effect. CONCLUSIONS: Treatment with MFNS 100 microg once daily for 1 year was well tolerated in children 6-11 years old, with negligible systemic exposure and no evidence of suppression of the hypothalamic-pituitary-adrenal axis or ocular changes.

Combination therapy with azelastine hydrochloride nasal spray and fluticasone propionate nasal spray in the treatment of patients with seasonal allergic rhinitis.

BACKGROUND: To our knowledge, there are no published studies that evaluated the efficacy of azelastine hydrochloride nasal spray in combination with an intranasal corticosteroid, although anecdotal reports of the use of these agents in combination are common. OBJECTIVE: To determine if greater efficacy could be achieved with the intranasal antihistamine azelastine and the intranasal corticosteroid fluticasone propionate used concurrently compared with the efficacy of each agent alone. METHODS: This randomized, 2-week, multicenter, double-blind trial was conducted during the Texas mountain cedar season. After a 5-day placebo lead-in period, 151 patients with moderate to severe nasal symptoms were randomized to treatment with the following: (1) azelastine nasal spray, 2 sprays per nostril twice daily; (2) fluticasone nasal spray, 2 sprays per nostril once daily; or (3) azelastine nasal spray, 2 sprays per nostril twice daily, plus fluticasone nasal spray, 2 sprays per nostril once daily. The primary efficacy variable was the change from baseline in the total nasal symptom score (TNSS), consisting of sneezing, itchy nose, runny nose, and nasal congestion. RESULTS: All 3 groups had statistically significant (P < .001) improvements from their baseline TNSS after 2 weeks of treatment. The TNSS improved 27.1% with fluticasone nasal spray, 24.8% with azelastine nasal spray, and 37.9% with the 2 agents in combination (P < .05 vs either agent alone). All 3 treatments were well tolerated. CONCLUSIONS: The significant improvement in the TNSS with combination therapy relative to the individual agents alone is in contrast to previously published studies that found no advantage with an oral antihistamine and an intranasal corticosteroid in combination. Azelastine nasal spray and fluticasone nasal spray in combination may provide a substantial therapeutic benefit for patients with seasonal allergic rhinitis compared with therapy with either agent alone.

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

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.

Efficacy and safety of ciclesonide nasal spray for the treatment of seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR), an inflammatory disease of the nasal mucosa, affects approximately 25% of adults and 40% of children in the United States. Ciclesonide nasal spray is a corticosteroid being developed as a hypotonic formulation for AR. OBJECTIVE: We sought to evaluate the efficacy, safety, and tolerability of ciclesonide nasal spray in adult and adolescent patients with seasonal AR (SAR). METHODS: In this double-blind study patients (age, >or=12 years) were randomized to receive 200 microg of intranasal ciclesonide (n = 164) or placebo (n = 163) once daily for 28 days. The primary measure was morning and evening patient-assessed reflective total nasal symptom score (TNSS). Additionally, instantaneous TNSSs, physician-assessed overall nasal signs and symptoms severity, and the results of the Rhinoconjunctivitis Quality of Life Questionnaire were evaluated. Adverse events were monitored throughout the study. RESULTS: Ciclesonide significantly improved average morning and evening reflective and instantaneous TNSSs compared with placebo over days 1 to 14 (P < .001). Improvements were also noted over days 1 to 28 (P < .001) and over days 15 to 28 (P = .011). Ciclesonide was well tolerated. CONCLUSION: Intranasal ciclesonide was superior to placebo in relieving nasal symptoms in adult and adolescent patients with SAR. These results confirm the dose range-finding study in patients with SAR and support the efficacy of ciclesonide in AR. CLINICAL IMPLICATIONS: In a clinical setting ciclesonide was shown to be safe and effective in the treatment of SAR in adolescent and adult patients.

Validation of the nighttime symptoms score as a clinically relevant measure of allergic rhinitis.

The aim of this study was to validate the nighttime symptoms score (NSS), which incorporates individual scores for difficulty going to sleep and nighttime awakening caused by nasal symptoms and nasal congestion on awakening, as a clinically relevant measure of allergic rhinitis (AR). Fifty-five general season AR (SAR) symptom items were generated by interviews with 14 patients with symptomatic SAR without concomitant asthma for use in an Importance Rating Questionnaire (IRQ). A second group of patients (n = 83) with symptomatic AR without asthma rated the importance of each item on the IRQ. Correlation coefficients were calculated to examine the relationships between the six sleep quality questions on the IRQ and the other AR symptoms and between the symptom questions of the NSS, the Daytime Nasal Symptoms Score (DNSS), and the individual domains of the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). The majority (94%) of patients with active AR reported some degree of symptoms relating to sleep quality. The six sleep quality items on the IRQ were selected by 71-84% of patients. The sleep quality items were more highly correlated with each other (r = 0.48-0.85) than with the four items of the DNSS (r = 0.01-0.42). There was a moderate-to-strong correlation of the RQLQ sleep domain with the two sleep questions of the NSS (r = 0.44-0.57). The individual symptom questions of the NSS and the DNSS were only moderately correlated with each other. Sleep quality questions measure aspects of SAR that are not captured by daytime SAR symptoms. The results show that the NSS is a valid and relevant clinical measure of the impact of nighttime sleep disturbance on AR patients.