Efficacy and safety of GSP301 nasal spray in children aged 6 to 11 years with seasonal allergic rhinitis.

BACKGROUND: GSP301 nasal spray is a fixed-dose combination of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of GSP301 in pediatric patients (aged ≥6 to <12 years) with seasonal allergic rhinitis (SAR). METHODS: This double-blind, randomized, parallel-group study randomized 446 eligible patients 1:1 (GSP301 [olopatadine hydrochloride 665 µg and mometasone furoate 25 µg] or placebo) as 1 spray/each nostril twice daily for 14 days. The primary end point was change from baseline in average morning and evening subject-reported 12-hour reflective Total Nasal Symptom Score (rTNSS) over a 14-day treatment period analyzed using mixed-effect model repeated measures. Additional assessments included instantaneous Total Nasal Symptom Score, Pediatric Rhinoconjunctivitis Quality of Life Questionnaire, reflective Total Ocular Symptoms Score, instantaneous Total Ocular Symptoms Score, individual symptoms, Physician-assessed Nasal Symptom Score, and adverse events. RESULTS: GSP301 showed clinically meaningful and statistically significant improvement in rTNSS vs placebo (-0.6; 95% confidence interval, -0.9 to -0.2; P = .001). Statistically significant improvements favoring GSP301 were shown for all individual rTNSS symptoms, instantaneous Total Nasal Symptom Score, and most of its individual symptoms, Physician-assessed Nasal Symptom Score (P = .01), and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (P < .001). For ocular symptoms, numerical improvements favoring GSP301 were observed, with statistical significance achieved only for reflective "tearing/watering eyes" (P = .04). Treatment-emergent adverse events occurred in 12.0% and 10.4% of patients in the GSP301 and placebo groups, respectively. One subject (0.5%) (placebo group) experienced a serious adverse event (suspected viral meningitis) that was not related to the study treatment and was resolved. CONCLUSION: GSP301 was well tolerated and efficacious for treating SAR symptoms in pediatric patients and showed a favorable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03463031.

Referrals, etiology, prevalence, symptoms, and treatments of chronic cough: A survey of allergy specialists.

BACKGROUND: Chronic cough (CC) affects 11% of the US adult population, and these patients experience persistent symptoms despite adherence to recommended treatment protocols. Further research is needed to identify effective therapies to treat CC. OBJECTIVE: To describe the referral sources, etiology, prevalence, symptoms, and treatments for patients diagnosed with having CC who present to allergy specialists (AS). METHODS: An online survey was administered to 177 AS. The survey queried each AS experience with patients with CC, including the prevalence of CC, source of referrals for patients with CC, and perceived efficacy of treatments. RESULTS: A total of 103 (58%) AS reported that the patients with CC they treated were primarily of female sex (58.26%) and White (65.69%). Family physicians, nurse practitioners, physician assistants, and primary care internists were the most common source of referrals of patients with CC to AS. Furthermore, 20% of the respondents reported a complete resolution of the symptoms for more than 75% of their patients with CC. The top 4 "very common complaints" reported by the patients with CC were social embarrassment, loss of sleep, decreased quality of life, and sleep disruption. The top 4 most frequent treatments prescribed for CC were antireflux treatments, inhaled corticosteroids alone or in combination with long-acting ß-agonist, short-acting bronchodilators, and first-generation antihistamines. None of the therapies were rated "very effective" in greater than 50% of the patients with CC. CONCLUSION: The available treatments for CC do not effectively resolve the symptoms of this condition, and additional treatments need to be developed.

Long-term safety and efficacy of olopatadine-mometasone combination nasal spray in patients with perennial allergic rhinitis.

Background: Safety and efficacy of GSP301 nasal spray, an investigational fixed-dose combination of olopatadine hydrochloride and mometasone furoate, was established in three large, 2-week seasonal allergic rhinitis studies. Objective: To evaluate long-term (52 weeks) safety and efficacy of GSP301 in patients with perennial allergic rhinitis (PAR). Methods: In this randomized, double-blind, parallel-group study, 601 patients (ages ≥ 12 years) with PAR were randomized 4:1:1 to twice-daily GSP301 (olopatadine 665 µg and mometasone 25 µg [pH 3.7]) or two GSP301 vehicle formulations (placebo pH 3.7 or 7.0). Safety (primary end point) was monitored through adverse events (AE), laboratory assessments, vital signs, and physical examinations at weeks 30 and 52. The change from baseline in the average A.M. reflective Total Nasal Symptom Score (rTNSS) and instantaneous Total Nasal Symptom Score (iTNSS), Physician-assessed Nasal Symptom Scores (PNSS), and quality of life were assessed for GSP301 versus placebo pH 3.7 (p < 0.05 was considered statistically significant). Results: At week 52, treatment-emergent AEs (TEAE) occurred in 51.7, 41.4, and 53.5% of patients in the GSP301, placebo pH 3.7 and placebo 7.0 groups, respectively. No clinically meaningful differences were observed in TEAE incidences or other safety assessments across treatments. At weeks 6 and 30, GSP301 provided significant and clinically meaningful improvements in average rTNSS and iTNSS versus placebo pH 3.7 (p < 0.01, all comparisons). Similarly, at week 52, GSP301 provided significant and clinically meaningful improvements in rTNSS (least-squares mean difference -0.91 [95% confidence interval {CI}, -1.35 to -0.47]; p < 0.001), and iTNSS (least-squares mean difference -0.75 [95% CI, -1.17 to -0.33]; p < 0.001) versus placebo pH 3.7, with significant improvements in each individual symptom (p < 0.05, all comparisons). PNSS and quality of life were significantly improved versus placebo pH 3.7 at weeks 6 and 30 (p < 0.05, all comparisons), but these greater improvements did not reach statistical significance at week 52 (PNSS, p = 0.552; quality of life, p = 0.790). Conclusion: Twice-daily GSP301 was well tolerated and provided statistically significant and clinically meaningful improvements in PAR nasal symptoms versus placebo over 52 weeks and demonstrated a favorable safety profile and efficacy.Clinical trial NCT02709538, www.clinicaltrials.gov.

A review of the clinical efficacy and safety of MP-AzeFlu, a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate, in clinical studies conducted during different allergy seasons in the US.

A novel intranasal formulation of azelastine HCl (AZE, an antihistamine) and fluticasone propionate (FP, a corticosteroid) in a single spray (MP-AzeFlu [Dymista®]) was studied in four randomized, double-blind, placebo-controlled trials of patients with seasonal allergic rhinitis conducted in the US. Study sites were distributed so that all major US geographic regions and the prevalent pollens within these regions were represented. Spring and summer studies included patients aged 12 years and older with allergy to grass and tree pollens. Fall studies enrolled patients with allergy to weeds, in particular ragweed. In addition, a study was conducted during the winter months in patients with allergy to mountain cedar pollen in TX, USA. Regardless of allergy season or prevalent pollen, MP-AzeFlu improved nasal symptoms of allergic rhinitis (AR) to a significantly greater degree than AZE or FP, two treatments that currently are recommended as the first-line AR therapy. MP-AzeFlu improved all individual AR symptoms and was significantly better than FP and AZE for nasal congestion relief, which is generally accepted as the most bothersome symptom for AR patients. The onset of action was within 30 minutes. MP-AzeFlu also provided clinically important improvement in the overall Rhinoconjunctivitis Quality of Life Questionnaire score and significantly improved ocular symptoms of rhinitis compared to placebo. Favorable characteristics of the MP-AzeFlu formulation as well as superior clinical efficacy make it an ideal intranasal therapy for AR.

Safety of house dust mite sublingual immunotherapy standardized quality tablet in children allergic to house dust mites.

BACKGROUND: Sublingual immunotherapy (SLIT) tablets could be an important alternative to subcutaneous immunotherapy for house dust mite (HDM) allergy in children. OBJECTIVE: To characterize the safety, tolerability, and duration of local adverse events (AEs) of an HDM SLIT tablet (MK-8237; Merck, ALK Abellò, and Torii) in North American children 12 to 17 years old with HDM allergic rhinitis with and without conjunctivitis and with or without asthma. METHODS: In this phase 1, multicenter, double-blinded, randomized trial (NCT01678807), children received placebo, HDM SLIT tablet 6 standardized quality (SQ) HDM, or 12 SQ-HDM once daily for 28 days. The primary end point was the proportion of subjects with treatment-emergent AEs receiving active treatment vs placebo. The secondary end point was the proportion of subjects who discontinued owing to AEs. RESULTS: In total 195 subjects were randomized. The 2 HDM SLIT tablet doses were well tolerated. No anaphylactic reactions, systemic allergic reactions, AEs requiring epinephrine, serious AEs, or local swellings in the mouth or throat assessed as severe were reported. The proportion of subjects with treatment-emergent AEs was 54% with 6 SQ-HDM and 57% with 12 SQ-HDM (nonsignificant vs 43% with placebo). Local AEs were the most commonly reported treatment-emergent AEs. On day 1, the median duration of individual local AEs ranged from 1 to 43 minutes. The proportion of subjects who discontinued owing to AEs was 0%, 6.2%, and 6.2%, and who experienced treatment-related AEs was 25%, 45%, and 52% for the placebo, 6 SQ-HDM, and 12 SQ-HDM groups, respectively. CONCLUSION: The 6 and 12 SQ-HDM doses of the HDM SLIT tablet MK-8237 were well tolerated, and local AEs were of short duration. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01678807.

Bronchodilation with mometasone furoate/formoterol fumarate administered by metered-dose inhaler with and without a spacer in children with persistent asthma.

BACKGROUND: The bronchodilatory effect of mometasone furoate/formoterol fumarate (MF/F) administered by metered-dose inhaler (MDI) with or without a spacer has not been evaluated previously in children aged 5-11 years. METHODS: This was a randomized, multicenter, placebo-controlled, single-dose, four-period crossover study. Children with persistent asthma aged 5-11 years participated in this study. Subjects used inhaled corticosteroids with/without long-acting beta-2 agonists for 12 weeks before enrollment and at screening had forced expiratory volume in 1 sec (FEV1 ) ≥70% predicted. Subjects received MF/F MDI 100/10 µg with/without spacer (AeroChamber Plus® with Flow-Vu® Anti-Static Valved Holding Chamber), F-Dry Powder Inhaler (F-DPI) 10 µg, and placebo MDI with/without spacer in separate treatment periods. The primary endpoint was FEV1 area under the curve from 0 to 12 hr (AUC0-12hr ) for the comparison of MF/F with spacer versus placebo. Secondary measurements included MF/F without spacer versus placebo, as well as MF/F with spacer versus MF/F without spacer, and F-DPI versus placebo. Analysis was performed with an analysis of covariance model for a crossover study. RESULTS: Data from 87 subjects were analyzed. MF/F with spacer demonstrated a larger change in mean FEV1 AUC0-12hr versus placebo (115 vs. -9 mL), with a treatment difference of 124 mL (95% CI 94-154, P < 0.001). Similarly, MF/F without spacer versus placebo resulted in a 102 mL difference in mean-adjusted FEV1 AUC0-12hr (95% CI 73-131, P < 0.001), whereas the difference between MF/F with spacer versus MF/F without spacer was 22 mL (95% CI -8 to 52, P = 0.144). The difference between F-DPI versus placebo was 106 mL (95% CI 77-135, P < 0.001). No unexpected adverse events were observed. CONCLUSIONS: In this trial, MF/F MDI 100/10 µg demonstrated significant bronchodilation in children aged 5-11 years regardless of the use of a spacer. No difference in bronchodilation was observed between MF/F MDI and F-DPI.

A patient preference and satisfaction study of ciclesonide nasal aerosol and mometasone furoate aqueous nasal spray in patients with perennial allergic rhinitis.

Patients' preference and satisfaction with their nasal allergy medications may be influenced by their sensory attributes. This study evaluates patient preference and satisfaction with ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) compared with mometasone furoate aqueous nasal spray (MFNS). Symptomatic subjects with perennial allergic rhinitis (PAR) were randomized to CIC-HFA at 74 micrograms or MFNS at 200 micrograms q.d. in an open-label, two-period, crossover study. Subject preference was recorded as total preference score (TPS; average of 17 individual preference items) at the end of treatment period 2, and satisfaction was assessed with a 76-item, self-administered instrument at baseline and at the end of each 2-week treatment period. The primary assessments were TPS and regimen attributes composite satisfaction score composed of two of nine satisfaction subscales: sensory impact (including medication running out of the nose, medication running down the throat, and impact on smell and taste) and regimen management (comprised of issues relating to dosing and ability to remember to take medication). Two hundred ninety-four subjects completed the study. A total of 68.1% of subjects preferred CIC-HFA (p < 0.0001 versus MFNS), with a mean TPS of 68.3 versus 31.7 for the MFNS group. The regimen attributes composite satisfaction score significantly (p < 0.0001 for each treatment period) favored CIC-HFA versus MFNS at the end of treatment period 1 (85.5 vs 77.6) and treatment period 2 (83.0 versus 73.5), respectively. In this study, subjects reported higher preference for and satisfaction with CIC-HFA compared with MFNS, suggesting significant differences in patient perception of attributes in favor of CIC-HFA. Clinical trial registration URL and registration number: www.clinicaltrials.gov/ct2/show/NCT01401465.

Efficacy, safety, and optimal dose selection of beclomethasone dipropionate nasal aerosol for seasonal allergic rhinitis in adolescents and adults.

OBJECTIVE: Some patients with allergic rhinitis (AR) may prefer nonaqueous intranasal corticosteroid aerosols because of unwanted attributes of aqueous formulations. The mandatory removal of chlorofluorocarbon-propelled nonaqueous aerosols from the market limited available treatment options. To fulfill this unmet need, a nonaqueous, hydrofluoroalkane-propelled beclomethasone dipropionate (BDP) nasal aerosol was developed and approved for treatment of AR nasal symptoms. As part of the development program, this dose-ranging study evaluated three doses of BDP nasal aerosol to determine the optimally safe and effective dose for adolescent and adult patients (≥12 years old) with seasonal AR (SAR). METHODS: After a 7 to 21 day placebo run-in period, eligible patients with SAR were randomly assigned to once-daily BDP nasal aerosol 80 µg, 160 µg, 320 µg, or placebo. The primary endpoint was the change from baseline in average a.m. and p.m. patient-reported reflective total nasal symptom scores (rTNSS) over 2 weeks. Safety and tolerability were also assessed. A potential study limitation could be lack of objective assessment of AR symptoms. RESULTS: Significant improvements were seen in average a.m. and p.m. rTNSS (least squares [LS] mean treatment difference, -0.63; 95% CI: -1.13, -0.13; p = 0.013) as well as in average a.m. and p.m. instantaneous TNSS (iTNSS; LS mean treatment difference, -0.60; 95% CI: -1.09, -0.11; p = 0.016) with BDP nasal aerosol 320 µg/day compared with placebo. Although there were numerical improvements from baseline in patient-reported rTNSS and iTNSS with BDP nasal aerosol 80 µg and 160 µg, these doses did not achieve statistical significance compared with placebo. BDP nonaqueous nasal aerosol was well tolerated at all doses tested, with a safety profile comparable to that of placebo. CONCLUSIONS: These data indicate that 320 µg/day of BDP nasal aerosol is the optimally safe and effective dose for the treatment of SAR in adolescent and adult patients. Trial registration NCT: #NCT00854360.

Mometasone furoate nasal spray plus oxymetazoline nasal spray: short-term efficacy and safety in seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) and associated congestion adversely affect patients' lives. The intranasal corticosteroid mometasone furoate nasal spray (MFNS) is effective for AR symptoms including nasal congestion, and the intranasal decongestant oxymetazoline (OXY) is effective against nasal congestion, but the combination has not been fully studied. This study was designed to assess the efficacy of the combination of MFNS and OXY for the relief of seasonal allergic rhinitis (SAR) symptoms. METHODS: This phase 2 controlled clinical trial randomized adolescent and adult subjects (≥12 years; 2-year SAR) to MFNS q.d. (200 µg) + 3 sprays/nostril of OXY 0.05% (MFNS + OXY3); MFNS q.d. + 1 spray/nostril of OXY (MFNS + OXY1); MFNS q.d.; OXY b.i.d.; or placebo for 15 days, with 1-week follow-up. Coprimary end points were change from baseline in morning/evening (A.M./P.M.) instantaneous (NOW) total nasal symptom score (TNSS) over days 1-15 and AUC (AUC[0-4 hr]) change from baseline in day 1 congestion. RESULTS: In 705 subjects, both combinations reduced A.M./P.M. NOW TNSS over days 1-15 significantly more than OXY b.i.d. or placebo (p ≤ 0.002). Mean standardized AUC(0-4 hr) day 1 congestion change from baseline was significantly greater in combination and OXY b.i.d. groups (MFNS + OXY3, -0.92; MFNS + OXY1, -0.80; OXY b.i.d., -1.06) versus placebo (-0.57) and MFNS q.d. (-0.63). Combinations and MFNS q.d. were significantly effective for A.M./P.M. NOW TNSS over each weekly period; OXY b.i.d. was superior to placebo in week 1. Adverse events (AEs) were few and similar across treatments; one MFNS q.d. and one placebo subject experienced a serious AE, with neither considered treatment related. CONCLUSION: Combining MFNS with OXY relieves SAR symptoms, including congestion, with faster onset of action than MFNS q.d. and better sustained efficacy than OXY b.i.d.

A randomized, double-blind, placebo-controlled study assessing the safety and tolerability of regadenoson in subjects with asthma or chronic obstructive pulmonary disease.

BACKGROUND: Adenosine receptor stress agents for myocardial perfusion imaging (MPI) may cause A(2B) and/or A(3) receptor-mediated bronchoconstriction, of particular concern to physicians testing patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS: A Phase 4, randomized, double-blind study (NCT00862641) assessed the safety of the selective A(2A) receptor agonist, regadenoson, compared with placebo in subjects with asthma or COPD who represented likely candidates for MPI. RESULTS: Overall, 356 and 176 subjects with asthma and 316 and 151 subjects with COPD received regadenoson and placebo, respectively. The percentage of subjects experiencing a >15% decrease in FEV(1) from baseline to any assessment up to 24 hours post-baseline was not statistically significantly different between the regadenoson and the placebo groups in the asthma or COPD stratum. Dyspnea, the most frequent respiratory adverse event, occurred with higher incidence (P < .0001) in the regadenoson group than the placebo group in the asthma (10.7% vs 1.1%) and COPD (18.0% vs 2.6%) strata. No subjects experienced severe bronchoconstriction, although the occurrence of such reactions with adenosine receptor agonists cannot be ruled out, such that caution is advised. CONCLUSIONS: This information may be helpful to physicians selecting a pharmacologic stress agent for MPI in patients with asthma or COPD.

Mometasone furoate nasal spray reduces the ocular symptoms of seasonal allergic rhinitis.

BACKGROUND: Mometasone furoate nasal spray (MFNS), a potent intranasal corticosteroid with proved efficacy in relieving nasal allergic rhinitis symptoms, has demonstrated effectiveness in improving ocular symptoms associated with seasonal allergic rhinitis (SAR) in retrospective analyses. OBJECTIVE: We sought to evaluate prospectively the efficacy of MFNS in reducing total ocular symptom scores (TOSSs) and individual ocular symptoms in subjects with SAR. METHODS: Subjects 12 years or older (n = 429) with moderate-to-severe baseline symptoms were randomized to MFNS, 200 microg once daily, or placebo in this 15-day, double-blind, parallel-group study. Subjects evaluated morning instantaneous TOSSs and daily reflective TOSSs, total nasal symptom scores (TNSSs; both instantaneous TNSSs and reflective TNSSs, respectively), and individual ocular and nasal symptoms. Mean changes from baseline averaged over days 2 to 15 (instantaneous) and days 1 to 15 (reflective) were calculated. Quality of life was assessed by using the Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS: MFNS treatment yielded significant reductions from baseline versus placebo in instantaneous TOSSs (-0.34, P = .026, coprimary end point), instantaneous TNSSs (-0.88, P < .001, coprimary end point), reflective TOSSs (-0.44, P = .005), and reflective TNSSs (-1.06, P < .001). Significant decreases in all individual reflective ocular symptoms and instantaneous eye itching/burning and eye watering/tearing were observed for MFNS versus placebo (P < .05). Numeric improvements in instantaneous eye redness were seen but did not reach statistical significance. Improvements in Rhinoconjunctivitis Quality of Life Questionnaire total scores and individual symptom domains were achieved with MFNS treatment versus placebo (P < .001). MFNS was well tolerated. CONCLUSION: This prospective study demonstrates that MFNS significantly reduces ocular symptoms in subjects with SAR.

Safety of fixed-dose loratadine/montelukast in subjects with allergic rhinitis.

The safety of loratadine (second-generation antihistamine) and montelukast (leukotriene receptor antagonist) as monotherapies is well documented. Safety of the fixed-dose, single-tablet therapy loratadine/montelukast (L/M; SCH 445761, containing loratadine [10 mg]/montelukast [10 mg]), for treatment of the symptoms of allergic rhinitis in >3800 subjects is described. Safety data from 19 randomized clinical studies in which subjects were administered L/M are presented. Adverse events (AEs) were defined as any unfavorable and unintended sign, symptom, or laboratory data, including onset of new illness and exacerbation of preexisting conditions. Only AEs with an onset during the treatment period (i.e., treatment emergent) are summarized. Safety was also assessed via clinical laboratory evaluations and monitoring of vital signs and electrocardiogram (ECG). Overall, the incidence of AEs reported with L/M in the 19 studies was low and comparable with placebo, loratadine monotherapy, and montelukast monotherapy. The most frequently reported AE across all studies was headache. Most AEs were not severe and the duration of such events was short lived. Three AEs (headache [4.5%], fatigue [1.2%], and pharyngolaryngeal pain [1.2%]), regardless of relation to treatment, were reported by >1% of subjects in the L/M treatment group of multiple-dose, placebo-controlled studies. There were no clinically significant changes in clinical laboratory analyses or in vital signs, physical findings, or ECG found to be clinically relevant. Administration of the fixed-dose, single-tablet formulation of L/M was well tolerated. In these clinical studies, the safety of L/M was comparable with placebo, loratadine, and montelukast.

Double-blind, placebo-controlled trial of reformulated azelastine nasal spray in patients with seasonal allergic rhinitis.

BACKGROUND: Azelastine nasal spray is a topical antihistamine with a distinctive taste that may be objectionable to some patients. The primary objectives of this clinical trial were (1) to determine if a reformulated azelastine nasal spray (Astepro) with sucralose as a taste-masking agent provides comparable efficacy to the original formulation (Astelin) and (2) to evaluate dose-response relationships between groups. METHODS: Eight hundred thirty-five patients with seasonal allergic rhinitis were randomized to six treatment groups: (1) original azelastine nasal spray, 1 spray/nostril b.i.d.; (2) reformulated azelastine, 1 spray/nostril b.i.d.; (3) placebo, 1 spray/ nostril b.i.d.; (4) original azelastine nasal spray, 2 sprays/nostril b.i.d., (5) reformulated, 2 sprays/nostril b.i.d.; and (6) placebo, 2 sprays/nostril b.i.d. The primary efficacy variable was the change from baseline to day 14 in total nasal symptom score (TNSS) consisting of runny nose, sneezing, itchy nose, and nasal congestion. RESULTS: Original azelastine nasal spray and the reformulated spray produced comparable improvements in the TNSS at both dosages. There was a dose-related difference in TNSS comparing the 1- and 2-spray dosages. The percentage changes from baseline in the TNSS in the 2-sprays/nostril dosage groups were 27.9% (p<0.001) with the reformulated nasal spray, 23.5% (p<0.01) with the original formulation, and 15.4% with placebo. The incidence of bitter taste was 7% with the reformulated spray and 8% with the original at the 2-sprays/nostril dosage. CONCLUSION: The results of this study showed efficacy both with original azelastine nasal spray and with the reformulated nasal spray and a clear dose-response difference between the 1- and 2-spray dosages.

Efficacy and safety of fixed-dose loratadine/montelukast in seasonal allergic rhinitis: effects on nasal congestion.

A need exists for safe, effective therapy for the relief of the symptoms of allergic rhinitis (AR) that also consistently relieves nasal congestion, the most common and bothersome symptom. This study was performed to assess efficacy and safety of a once-daily tablet containing 10 mg of loratadine, an antihistamine, and 10 mg of montelukast, a leukotriene antagonist (SCH 445761) versus placebo and pseudoephedrine (PSE; 240 mg once-daily formulation; active comparator). In a multicenter, parallel-group, double-blind, double-dummy, randomized study, 1095 subjects with documented history of seasonal AR and positive skin-prick test to a prevailing aeroallergen were treated for 15 days with fixed-dose combination loratadine/montelukast (L/M), PSE, or placebo. After randomization, subjects rated severity of nasal congestion and measured peak nasal inspiratory flow (PNIF) rate in the morning and evening. The change in quality of life from baseline was also assessed. L/M and PSE were significantly more effective than placebo in alleviating nighttime and daytime nasal congestion and improving PNIF rate, an objective measure of nasal obstruction. There were no significant differences between L/M and PSE for any efficacy analysis including improvement in the quality of life. Subjects treated with L/M experienced a similar incidence of total adverse events versus placebo and a lower incidence of total adverse events (including dizziness, insomnia, jitteriness, nausea, and dry mouth) versus PSE. Nasal decongestant activity of L/M was significantly higher than that of placebo and similar to that of PSE in symptomatic AR subjects. L/M showed a safety profile similar to placebo and was better tolerated than PSE. Thus, L/M offers a safe and efficacious alternative to PSE for the treatment of nasal congestion associated with AR.

Long-term safety and asthma control with budesonide/formoterol versus budesonide pressurized metered-dose inhaler in asthma patients.

Safety concerns have been raised regarding the regular use of long-acting beta(2)-adrenergic agonists (LABAs) alone or with inhaled corticosteroids (ICSs). The purpose of this study was to examine the long-term safety of budesonide/formoterol pressurized metered-dose inhaler (pMDI). This 52-week, double-blind study (SD-039-0728; n=708) included patients >or=12 years of age with moderate to severe persistent asthma previously receiving ICSs. After 2 weeks on budesonide pMDI 320 microg twice daily (b.i.d.), patients were randomized 3:1:1 overall to budesonide/formoterol pMDI 640/18 microg b.i.d., budesonide/formoterol pMDI 320/9 microg b.i.d., or budesonide pMDI 640 microg b.i.d. The incidence of adverse events (AEs) was similar across the groups. Drug-related AEs (>or=2% overall) were oral candidiasis, tremor, and pharyngolaryngeal pain. No clinically meaningful differences in laboratory, electrocardiogram, or Holter monitor variables were observed. The percentage of patients with >or=1 asthma exacerbation was significantly lower (p=0.006) with budesonide/formoterol 640/18 (12.2%) and numerically lower with budesonide/formoterol 320/9 (14.4%) versus budesonide (21.8%). The number of asthma exacerbations per patient-treatment year was lower with budesonide/formoterol 640/18 (0.174; p=0.004) and budesonide/formoterol 320/9 (0.185; p=0.049) versus budesonide (0.315). Improvements in forced expiratory volume in 1 second and diary variables were significantly greater (p<0.001) with both budesonide/formoterol doses versus budesonide. Budesonide/formoterol 640/18 and 320/9 microg b.i.d. showed an acceptable safety profile relative to budesonide, with no significant or unexpected patterns of abnormalities observed by adding a LABA to budesonide for up to 1 year in this patient population. Improvements in asthma control were shown with both doses of budesonide/formoterol versus budesonide.

Asthma 2008: targeting immunoglobulin E to achieve disease control.

Traditionally, practice guidelines have recommended a step-wise approach to treatment based on asthma severity and lung function. However, increasing evidence suggests that asthma may not be adequately controlled in many patients with moderate-to-severe disease despite aggressive therapy, and that regularly evaluating the level of asthma control achieved in individual patients may be more effective than disease severity in guiding treatment decisions. This is reflected in updated asthma guidelines from the National Asthma Education and Prevention Program, which advocate regular assessment of asthma control in terms of the current impairment and future risk associated with the disease. Guideline-recommended options for patients with persistent, moderate-to-severe immunoglobulin E (IgE)-mediated asthma have recently been enhanced by the inclusion of omalizumab. This change is based on growing evidence for the central role of IgE in airway inflammation and asthma and the clinical effectiveness of blocking IgE with omalizumab, a recombinant humanized monoclonal antibody. Omalizumab significantly reduced asthma exacerbations and improved lung function and symptoms in randomized controlled studies of patients inadequately controlled on inhaled corticosteroids plus long-acting beta(2)-agonist therapy; these benefits for reducing asthma impairment and risk were maintained during steroid dose reductions. Omalizumab is well tolerated, although patients should be monitored for possible rare anaphylactic reactions.

Role of long-acting beta2-adrenergic agonists in asthma management based on updated asthma guidelines.

PURPOSE OF REVIEW: This review examines the role of long-acting beta2-adrenergic agonists in the management of asthma, particularly focusing on recommendations in the newly revised Global Initiative for Asthma (GINA) and National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines. RECENT FINDINGS: GINA guidelines recommend increasing inhaled corticosteroid doses in all children with asthma not controlled on low-dose inhaled corticosteroids before adding a long-acting beta2-adrenergic agonist, whereas NHLBI guidelines have different age-based recommendations for children. In patients younger than 5 years, NHLBI guidelines recommend increasing the inhaled corticosteroid dose before adding a long-acting beta2-adrenergic agonist; in children aged 5-11 years, equal weight is given to increasing the inhaled corticosteroid dose or including add-on therapy to low-dose inhaled corticosteroids. In adults and adolescents aged 12 years and older, GINA recommends adding long-acting beta2-adrenergic agonists to low-dose inhaled corticosteroids over increasing the inhaled corticosteroid dose. NHLBI guidelines give equal weight to these choices, with alternative, although not preferred, therapies including the addition of theophylline, zileuton, or leukotriene receptor antagonists to low-dose inhaled corticosteroids. SUMMARY: In the recently updated GINA and NHLBI asthma guidelines, long-acting beta2-adrenergic agonists are an important class of agents for the management of persistent asthma in patients whose asthma is not well controlled with inhaled corticosteroid monotherapy.

Formoterol dry-powder inhaler for the treatment of asthma and chronic obstructive pulmonary disease.

Formoterol, a long-acting beta2-adrenergic agonist, is used as an inhaled bronchodilator therapy for patients with asthma or for the prevention of exercise-induced bronchospasm in children and in chronic obstructive pulmonary disease. Formoterol has unique characteristics of rapid onset and sustained duration of action compared with other bronchodilators. In addition to its effectiveness as regular maintenance therapy in asthma and chronic obstructive pulmonary disease, formoterol is also reported to be effective as an as-needed reliever therapy in patients with asthma. Formoterol is available in several different types of dry-powder inhalers and pressurized metered-dose inhalers.

Efficacy and safety of azelastine nasal spray at a dose of 1 spray per nostril twice daily.

BACKGROUND: Azelastine hydrochloride nasal spray is available worldwide for the treatment of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis. One spray per nostril twice daily is the most commonly recommended dose. OBJECTIVE: To determine the efficacy and safety of azelastine nasal spray, 1 spray per nostril twice daily, in patients with SAR. METHODS: In 2 studies conducted in the United States we assessed 554 patients with moderate-to-severe SAR who were still symptomatic after a 1-week placebo lead-in period. Patients were randomized to 2 weeks of double-blind treatment with azelastine nasal spray, 1 spray per nostril twice daily, or placebo nasal spray. The primary efficacy variable was change from baseline in total nasal symptom score, consisting of sneezing, itchy nose, runny nose, and nasal congestion. RESULTS: Mean differences in total nasal symptom score between the azelastine and placebo groups were significant in both studies: 2.69 vs 1.31 (P = .01) in study 1 and 3.68 vs 2.50 (P = .02) in study 2. Bitter taste was reported by 8.3% of patients treated with 1 spray per nostril twice daily compared with the labeled incidence of 19.7% with 2 sprays per nostril twice daily. Somnolence was reported by 1 patient (0.4%) using the 1-spray regimen compared with the labeled incidence of 11.5% using the 2-spray regimen. CONCLUSIONS: Azelastine nasal spray at a dose of 1 spray per nostril twice daily is effective and has improved tolerability compared with 2 sprays per nostril twice daily in patients with SAR.

Long-term safety and efficacy of intranasal ciclesonide in adult and adolescent patients with perennial allergic rhinitis.

BACKGROUND: Ciclesonide is a corticosteroid in development for allergic rhinitis that has been shown to be safe and effective in seasonal allergic rhinitis and perennial allergic rhinitis (PAR) trials of up to 6 weeks in duration. However, the long-term safety and efficacy of ciclesonide are unknown. OBJECTIVE: To demonstrate the long-term safety of intranasal ciclesonide, 200 microg once daily, in patients with PAR. METHODS: Patients (> or = 12 years old) with a 2-year or longer history of PAR were randomized in a double-blind fashion to receive ciclesonide, 200 microg, or placebo once daily in the morning for up to 52 weeks. Spontaneous and elicited adverse events were monitored throughout the study. Ear, nose, and throat examinations were performed to evaluate local tolerability. Additionally, 24-hour urinary free cortisol level, morning plasma cortisol level, intraocular pressure, and lens opacification were monitored to evaluate the systemic safety of intranasal ciclesonide. Ciclesonide efficacy was determined by measuring 24-hour reflective total nasal symptom scores. RESULTS: No clinically relevant differences were observed between the ciclesonide and placebo groups in adverse events, ear, nose, and throat examinations, or 24-hour urinary free or morning plasma cortisol levels. Similarly, no clinically relevant differences were found between treatment groups in intraocular pressure, visual acuity, or lens opacification. With regard to efficacy, ciclesonide achieved a significantly greater reduction in 24-hour reflective total nasal symptom score compared with placebo over more than 52 weeks (P < .001). CONCLUSION: In this study, intranasal ciclesonide, 200 microg once daily, was safe and effective for the long-term treatment of PAR, with no evidence of tachyphylaxis.