A double-blind, placebo-controlled trial of the efficacy and safety of two doses of azelastine hydrochloride in perennial allergic rhinitis.

Background: Azelastine hydrochloride (AZE) is a selective, non-sedating H1 antagonist with anti-inflammatory and mast cell stabilizing properties, which can be used as an alternative to intranasal corticosteroids. The objective of this study was to evaluate the efficacy of the new formulation of 0.15% AZE compared to that of the placebo at a dosage of two sprays per nostril twice daily for 4 weeks in patients with perennial allergic rhinitis (PAR). Materials and methods: A total of 581 subjects were randomized in this double-blind (DB) placebo-controlled trial (NCT00712920) that compared 0.10% (1,096 µg daily) and 0.15% AZE (1,644 µg daily) to the placebo in PAR patients. The study consisted of a 7-day single-blind placebo lead-in period and a 28-day DB treatment period. The primary endpoint was the change from baseline in the 12-h reflective total nasal symptom score (rTNSS) for the entire 28-day study period of 0.15% AZE, two sprays per nostril BID compared to the placebo. The efficacy and safety of 0.15% AZE were compared to the placebo. Results: Least square (LS) mean improvement from baseline in the morning (AM) and evening (PM) combined rTNSS was statistically significant for the 0.15% AZE group (p = 0.04) compared to the placebo group. LS mean improvement from baseline in the AM and PM combined rTNSS was 4.10 (4.26) units for 0.15% AZE and 3.81 (3.99) for 0.10% AZE. For individual symptoms, there was a statistically significant change in the LS mean (p = 0.04) improvement from baseline on the 12-h reflective assessment for the 0.15% AZE group for runny nose. Further numerical improvements were shown for itchy nose, nasal congestion, runny nose, and sneezing compared to the placebo. No deaths or serious adverse events related to the study medication were reported. Conclusion: The present formulation of 0.15% AZE is safe and effective in relieving PAR symptoms. It effectively relieves nasal and non-nasal symptoms. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT00712920.

Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: REALISE Randomized Clinical Trial Results.

BACKGROUND: Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-µg peanut protein (Viaskin Peanut 250 µg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children. OBJECTIVE: To examine the safety of VP250 in children, using a study design approximating potential real-world use. METHODS: REAL LIfe Use and Safety of EPIT (REALISE) is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported. RESULTS: Three hundred ninety-three children were randomized 3:1 to receive VP250 (n = 294) or placebo (n = 99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued because of adverse events (AEs). Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall, AE rates were similar among participants with and without a history of peanut anaphylaxis. CONCLUSIONS: In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

MP-AzeFlu in Moderate-to-Severe Allergic Rhinitis: A Literature Review.

Allergic rhinitis (AR) is prevalent, and many patients present with moderate-to-severe symptomatic disease. The majority of patients are not satisfied with their AR treatment, despite the use of concurrent medications. These gaps underscore the need for treatment with more effective options for moderate-to-severe AR. The authors' objective was to review systematically the efficacy and safety of MP-AzeFlu for the treatment of AR. The primary outcomes studied were nasal, ocular, and total symptoms. Other outcomes included time to onset and of AR control, quality of life, and safety. Searches of PubMed and Cochrane databases were conducted on May 14, 2020, with no date restrictions, to identify publications reporting data on MP-AzeFlu. Clinical studies of any phase were included. Studies were excluded if they were not in English, were review articles, did not discuss the safety and efficacy of MP-AzeFlu for AR symptoms. Treatment of AR with MP-AzeFlu results in effective, sustained relief of nasal and ocular symptoms, and faster onset and time to control compared with intranasal azelastine or fluticasone propionate. Long-term use of MP-AzeFlu was safe, with benefits in children, adults, and adults aged ≥65 years. Other treatment options, including fluticasone propionate and azelastine alone or the combination of intranasal corticosteroids and oral antihistamine, do not provide the same level of efficacy as MP-AzeFlu in terms of rapid and sustained relief of the entire AR symptom complex. Furthermore, MP-AzeFlu significantly improves patient quality of life. MP-AzeFlu is a currently available combination that may satisfy all these patient needs and expectations.

Treatment with azelastine hydrochloride and fluticasone propionate in a single delivery device of young children and adolescents with allergic rhinitis.

Background: Allergic rhinitis (AR) is the most common chronic noncommunicable disease worldwide that affects any age during the human life span but raises particular concerns among the parents and caregivers of the children who are affected. H1-receptor antagonists and corticosteroids provide the most effective way of bringing the condition under control. Intranasal application of these medications has the advantage of a faster onset of action and avoids systemic unwanted adverse effects. The only combination treatment, which comprises azelastine hydrochloride and fluticasone propionate, so far in a single advanced delivery system has proven its efficacy and safety in clinical trials of adult patients with AR. Objective: To critically review and identify gaps in the existing data for children in all different strata of pediatric ages. Methods: We searched the specialized medical literature for publications on the efficacy and safety of the combined formulation of azelastine and fluticasone in a single delivery device in adolescents (ages < 18 years) and children (ages < 12 years). Results: Altogether, 12 peer-reviewed articles have been published about trials that also involved subjects in different strata of the pediatric ages, seven of the articles pooled adolescents and adults. Three articles presented the results of studies in children ages 4 to 11 years specifically designed to overcome the difficulties that children experience in expressing themselves verbally. Conclusion: All the trials with the novel combination product that involved young children and adolescents documented its efficacy, effectiveness, and safety. However, the numbers of the youngest children (ages 4 and 5 years) were low, which suggested that further data about safety and efficacy in this age group are needed.

Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial.

STUDY OBJECTIVE: Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial. METHODS: Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded. RESULTS: Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (-1.6 versus -1.5; 95% confidence interval -0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%). CONCLUSION: Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center.

Evaluation of in vitro Penetration of Fluticasone Propionate from MP-AzeFlu and Fluticasone Propionate Nasal Spray Through EpiAirway™606 Tissues Using Vertical Diffusion Cells.

PURPOSE: Most patients with allergic rhinitis (AR) have moderate-to-severe disease, requiring complete and prompt relief when symptoms occur. The time course of fluticasone propionate (FP) penetration into nasal tissues after intranasal administration is not well characterized. The goal of this proof-of-concept study was to evaluate the mucosal penetration of FP from fixed-combination FP-azelastine nasal spray (MP-AzeFlu) compared with an FP-only nasal spray in an in vitro, 3-dimensional human bronchial tissue model. MATERIALS AND METHODS: Absorption of FP from MP-AzeFlu and FP nasal spray was modeled using EpiAirway™606 (MatTek Corporation; Ashland, MA, USA) tissue cultured in vertical diffusion cells. The dosing amount of MP-AzeFlu was optimized in a pilot study. Based on the results of the pilot study, 10 µL of MP-AzeFlu (3.65 µg; n = 8) and 10 µL of FP nasal spray (5.00 µg; n = 8) were evaluated for penetration of tissue. Tissue integrity was monitored with Lucifer yellow. FP in the receiving media was quantified for each sample using liquid chromatography with tandem mass spectrometry. RESULTS: MP-AzeFlu and FP nasal spray were associated with similar FP accumulation profiles in the receiving media, but the permeability of FP was greater for MP-AzeFlu during hours 0 to 6, suggesting faster absorption for MP-AzeFlu. No indications of compromised tissue integrity were found in any of the tested cells. CONCLUSION: The higher and more rapid penetration of FP from MP-AzeFlu supports the use of MP-AzeFlu for patients with AR, particularly when prioritizing fast and pronounced symptom relief.

A review of the efficacy and safety of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with asthma.

BACKGROUND: Despite current guidelines, many patients with asthma remain symptomatic, particularly those intolerant of, unresponsive to, or uncontrolled by long-acting beta 2-agonists (LABAs). Tiotropium bromide, delivered through the Respimat soft-mist inhaler in 2 puffs of 1.25 micrograms each, is approved for the long-term, maintenance treatment of asthma in patients aged ≥6 years. OBJECTIVE: An overview of the use of once-daily tiotropium Respimat 2.5 micrograms in adults and adolescents with varying degrees of asthma severity. The role of the parasympathetic nervous system in the pathophysiology of asthma, the development of tiotropium for respiratory disease, and the value of the Respimat inhaler are also discussed. METHODS: A literature search of all phase II and phase III trials of once-daily tiotropium Respimat 2.5 micrograms. RESULTS: Once-daily tiotropium Respimat 2.5 micrograms was studied in five phase III studies: three studies in adults and two in adolescents aged 12-17 years. Tiotropium Respimat 2.5 micrograms demonstrated efficacy in adults and adolescents with mild, moderate, or severe asthma, showing significant improvements in lung function and asthma control in patients with uncontrolled asthma despite inhaled corticosteroids (ICS) or ICS plus LABA use. The adverse event profile of tiotropium was very acceptable, with safety similar to placebo. CONCLUSION: Once-daily tiotropium Respimat 2.5 micrograms has positive attributes that include efficacy, a safety profile similar to placebo, once-daily dosing, administration by inhalation, and delivery in the easy-to-use and consistent-dosing Respimat device. However, more data are needed on the effects of tiotropium on clinical outcomes, patients' day-to-day lives, and real-world effectiveness.

Randomized, placebo-controlled study of cetirizine and loratadine in children with seasonal allergic rhinitis.

BACKGROUND: Pharmacologic treatment is a mainstay of allergy therapy and many caregivers use over-the-counter antihistamines for the treatment of seasonal allergic rhinitis (SAR) symptoms in children. OBJECTIVE: To assess the efficacy and safety of cetirizine 10 mg syrup versus loratadine 10 mg syrup versus placebo syrup in a randomized double-blind study of children, ages 6-11 years, with SAR. METHODS: This randomized, double-blind, parallel-group, placebo-controlled study was conducted at 71 U.S. centers during the spring tree and grass pollen season. After a 1-week placebo run-in period, qualified subjects were randomized to once-daily cetirizine 10 mg (n = 231), loratadine 10 mg (n = 221), and placebo (n = 231) for 2 weeks. The primary efficacy end point was change from baseline in the subject's mean reflective total symptom severity complex (TSSC) score over 14 days. RESULTS: Children treated with cetirizine experienced significantly greater TSSC score reductions versus children treated with placebo over 14 days (least square mean change, -2.1 versus -1.6; p = 0.006). The differences in TSSC score improvement over 14 days between the cetirizine versus loratadine groups (-2.1 versus -1.8; p = 0.124) and between the loratadine versus placebo groups (-1.8 versus -1.6; p = 0.230) were not statistically significant. Predominant adverse events in the cetirizine, loratadine, and placebo groups were headache (3.5, 3.6, and 3.1%, respectively) and pharyngitis (3.5, 2.7, and 3.5%, respectively). Somnolence was reported in three subjects (1.3%) treated with cetirizine and in none of the other subjects. CONCLUSION: Cetirizine 10 mg was statistically significantly more efficacious than placebo in the treatment of SAR symptoms in children ages 6-11 years. Symptom improvement was not significantly different between the loratadine 10 mg and placebo groups.

Diagnosis and management of allergic conjunctivitis in pediatric patients.

BACKGROUND: Allergic conjunctivitis (AC), although one of the most common ocular disorders in pediatric patients, is frequently overlooked, misdiagnosed, and undertreated in children. OBJECTIVE: To guide pediatric health care professionals in the optimal diagnosis and management of AC in pediatric patients. METHODS: To identify any existing best practice guidelines for the diagnosis and treatment of AC in pediatric patients, a review of the literature published between 2004 and January 2015 was conducted. Diagnosis and treatment algorithms and guidelines for pediatric patient referrals were then developed. RESULTS: A literature search to identify best practice guidelines for the treatment of AC in pediatric patients failed to return any relevant articles, which highlighted the need for best practice recommendations. Based on publications on adult AC and clinical experience, this review provides step-by-step guidance for pediatric health care professionals, including recognizing clinical features of AC, establishing a comprehensive medical history, and performing a thorough physical examination to ensure a correct diagnosis and the optimal treatment or referral to an eye care specialist or allergist when required. In addition to established drug treatments, the role of subcutaneous and sublingual immunotherapy is discussed to inform pediatric health care professionals about alternative treatment options for patients who do not tolerate pharmacotherapy or who do not respond sufficiently. CONCLUSION: The diagnostic and treatment algorithms and guidelines provided in this review help address the current literature and educational gap and may lead to improvements in diagnosis and management of pediatric AC.

Intranasal spray medications for maintenance therapy of allergic rhinitis.

BACKGROUND: Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR) by providing direct delivery of medication to the nasal mucosa, reducing the potential for systemic adverse effects, decreasing burden of disease, and improving quality of life. OBJECTIVE: To review currently available intranasal sprays indicated for maintenance therapy of AR in the United States: intranasal antihistamines (INAH); intranasal corticosteroids (INCS); and MP-AzeFlu, a single formulation nasal spray of the INAH, azelastine hydrochloride, and the INCS, fluticasone propionate. METHODS: MEDLINE searches were conducted to identify placebo-controlled studies of commercially available prescription nasal sprays at U.S.-approved doses and indications, and published after an earlier systematic review of AR treatment. Inclusion criteria were ≥20 subjects; duration of ≥2 weeks for seasonal (or episodic) AR, ≥4 weeks for perennial (or persistent) AR, and reporting a total nasal symptom score as a primary or secondary outcome. RESULTS: Twenty studies met the inclusion criteria: 4 pediatric, 16 adult/adolescent. There were 4 perennial AR studies (381 children, 1607 adults) and 16 seasonal AR trials (3081 children, 6548 adults). In these studies, 2451 subjects (481 children, 1970 adults) received an INCS, 3001 (1116 children, 1885 adults) received an INAH, and 346 adult subjects received MP-AzeFlu. All active treatments were well tolerated and effective as measured by the reduction in nasal symptoms. Head-to-head comparisons were only available for MP-AzeFlu versus the individual active agent components. MP-AzeFlu provided significantly greater symptom relief than either azelastine or fluticasone propionate alone and with an onset starting at 30 minutes after the dose. CONCLUSION: The most recent addition to intranasal sprays for the maintenance therapy of AR is MP-AzeFlu, a single formulation nasal spray of azelastine hydrochloride and fluticasone propionate in an advanced delivery system. Analysis of clinical data showed this to be the first new intranasal medication that provides greater clinical benefit than an INCS in treating AR.

Efficacy and safety of beclomethasone dipropionate nasal aerosol in children with perennial allergic rhinitis.

BACKGROUND: Beclomethasone dipropionate (BDP) nasal aerosol (non-aqueous) is approved for management of seasonal and perennial allergic rhinitis (PAR) in adolescents and adults. OBJECTIVE: To evaluate the efficacy and safety of BDP nasal aerosol at 80 µg/day in children with PAR. METHODS: This 12-week, phase 3, double-blinded, placebo-controlled, parallel-group study randomized 547 children (4-11 years old) with PAR to once-daily BDP nasal aerosol at 80 µg/day or placebo. The primary end point was change from baseline in average morning and evening reflective total nasal symptom score (rTNSS) during the first 6 weeks of treatment in patients 6 to 11 years old. Changes from baseline in average morning and evening instantaneous TNSS (iTNSS) in children 6 to 11 years old and average rTNSS and iTNSS in children 4 to 11 years old were assessed during the first 6 weeks of treatment. RESULTS: Improvements were significantly greater with BDP nasal aerosol than with placebo during the first 6 weeks of treatment in children 6 to 11 years old in average morning and evening rTNSS and iTNSS (mean treatment difference -0.66 [P = .002] and -0.58 [P = .004], respectively). Improvements in average morning and evening rTNSS and iTNSS also were significantly greater in patients 4 to 11 years receiving BDP nasal aerosol than with placebo during the first 6 weeks of treatment (P = .002 and P = .004, respectively). Similar improvements were seen during 12 weeks of treatment. The safety profile of BDP nasal aerosol was comparable to that of placebo. CONCLUSION: The BDP nasal aerosol at 80 µg/day in children 4 to 11 years old was well tolerated and effective in controlling nasal symptoms of PAR. TRIAL REGISTRATION: www.clinicaltrials.gov, identifier NCT01783548.

Flunisolide hydrofluoroalkane with integrated spacer for treating asthma: an updated review.

Flunisolide hydrofluoroalkane (HFA) with integrated spacer is the most recent reformulated inhaled corticosteroid (ICS) for asthma available in the United States. It is the only product that combines a corticosteroid extrafine aerosol with a built-in spacer. The potential clinical benefit of the flunisolide HFA formulation and its integrated spacer for treating persistent asthma was assessed through a comprehensive review of the published literature and data from the past 10 years focusing on (1) flunisolide, the molecule, and the impact of the HFA reformulation; (2) updated information on the anti-inflammatory response to flunisolide HFA, particularly in the distal airways; and (3) the usefulness of an integrated spacer. Flunisolide HFA was found effective and safe in clinical studies and comparable with the chlorofluorocarbon (CFC) formulation, but at about one-third the dose of flunisolide CFC, likely reflecting both the device and the particle size of the reformulated product. Compared with the CFC formulation, the extrafine aerosol and smaller particle size of flunisolide HFA substantially increased pulmonary deposition and decreased oropharyngeal deposition. The integrated spacer further enhanced the pulmonary/oropharyngeal deposition ratio. Examination of lung biopsy specimens indicated a favorable anti-inflammatory response to flunisolide HFA in peripheral airways. Pediatric studies showed no significant effects on growth. The data indicate that flunisolide HFA is a safe and effective maintenance therapy for asthma patients. The integrated spacer may provide an added advantage for patients, especially those who may be more likely to experience adverse effects of ICSs, both local and systemic, including children susceptible to adverse effects on growth.

Intranasal triamcinolone and growth velocity.

BACKGROUND: Inadequate designs and conflicting results from previous studies prompted the US Food and Drug Administration to publish guidelines for the design of clinical trials evaluating the effects of orally inhaled and intranasal corticosteroids on the growth of children. This study conformed to these guidelines to evaluate the effect of triamcinolone acetonide aqueous nasal spray (TAA-AQ) on the growth of children with perennial allergic rhinitis (PAR). METHODS: This randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluated the effect of once-daily TAA-AQ (110 µg) on the growth velocity (GV) of children aged 3-9 years with PAR by using stadiometry at baseline (4-6 months), during treatment (12 months), and at follow-up (2 months). Hypothalamus-pituitary-adrenal (HPA) axis function was assessed by measuring urinary cortisol levels. Details of adverse events were recorded. RESULTS: Of 1078 subjects screened, 299 were randomized, and 216 completed the study (placebo, 107; TAA-AQ, 109). In the primary analysis (modified intent-to-treat: placebo, 133; TAA-AQ, 134), least-squares mean GV during treatment was lower in the TAA-AQ group (5.65 cm/year) versus placebo (6.09 cm/year). The difference (-0.45 cm/year; 95% confidence interval: -0.78 to -0.11; P = .01), although clinically nonsignificant, was evident within 2 months of treatment and stabilized thereafter. At follow-up, the GV approached baseline (6.70 cm/year) in the TAA-AQ group (6.59 cm/year) and decreased slightly in the placebo group (5.89 cm/year vs 6.06 cm/year at baseline). No HPA axis suppression was observed. CONCLUSIONS: By using rigorous Food and Drug Administration-recommended design elements, this study detected a small, statistically significant effect of TAA-AQ on the GV of children with PAR.

Bronchodilator effect of single-dose formoterol administered by pressurized metered-dose inhaler in children with asthma aged 6 to <12 years receiving budesonide.

Dose-response of formoterol via pressurized metered-dose inhaler (pMDI) has not been determined in asthmatic pediatric patients aged 6 to <12 years. This study was designed to assess the bronchodilating dose-response of three formoterol pMDI doses in children with stable asthma aged 6 to <12 years receiving twice-daily (b.i.d.) budesonide 160 micrograms. A U.S., multicenter, five-way crossover study compared single doses of formoterol, a long-acting beta-agonist, via pMDI (2.25, 4.5, and 9 micrograms) or dry powder inhaler (12 micrograms; active comparator) and placebo, with a 3- to 14-day washout period between doses. Budesonide pMDI 160 micrograms, an inhaled corticosteroid, was given b.i.d. throughout the study. Fifty-four pediatric patients (mean age, 9.2 years; mean asthma history, 6.1 years) were randomized. All formoterol doses showed significantly higher average 12-hour forced expiratory volume in 1 second (FEV1; area under the curve) versus placebo (primary efficacy). Formoterol pMDI 4.5 and 9 micrograms showed significantly greater average 12-hour FEV1 than formoterol 2.25 micrograms (p = 0.0007 and p = 0.0001, respectively). Formoterol also resulted in significant improvement in maximum FEV1 during the 12-hour treatment period (secondary efficacy) with formoterol 4.5-, 9-, and 12-microgram doses versus placebo and the formoterol 2.25-microgram dose. Bronchodilation was not maintained during the 12-hour dosing interval with formoterol 2.25 micrograms. No serious adverse events were reported. Formoterol pMDI showed generally dose-proportional pharmacokinetics to 9 micrograms, as determined by urinary excretion. Single doses of formoterol pMDI showed a dose-response, with formoterol 9 micrograms exhibiting a maximum response, in pediatric patients aged 6 to <12 years with persistent stable asthma maintained on b.i.d. budesonide pMDI 160 micrograms. Clinical trial NCT01136655, www.clinicaltrials.gov.

Long-term, randomized safety study of MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in an advanced delivery system) in subjects with chronic rhinitis.

BACKGROUND: MP29-02 is a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate (FP) in an advanced delivery system for the treatment of seasonal allergic rhinitis. OBJECTIVE: The objective of this study was to evaluate the long-term safety of MP29-02 in subjects with chronic allergic (perennial) or nonallergic (vasomotor) rhinitis. METHODS: This was a 1-year, randomized, open-label, active-controlled, parallel-group study in subjects with chronic allergic or nonallergic rhinitis. A total of 612 subjects were randomized in a 2:1 ratio to (1) MP29-02, one spray per nostril twice daily (total daily doses of azelastine hydrochloride and FP were 548 mcg and 200 mcg, respectively); or (2) FP, 2 sprays per nostril once daily (total daily dose 200 mcg). Safety and tolerability assessments were made at months 1, 3, 6, 9, and 12. RESULTS: The incidence of treatment-related adverse events was low with both MP29-02 (9.4%) and FP (11.1%), with no evidence of late-occurring adverse events. Nasal examinations showed no evidence of nasal mucosal ulcerations or septal perforations with MP29-02, and the overall incidence of adverse findings was reduced as the study progressed. There were no unusual or unexpected ocular examination findings and no clinically important laboratory findings or clinically important differences between groups in fasting AM serum cortisol levels after 12 months of treatment. CONCLUSIONS: MP29-02 was well tolerated. There were no safety findings that would preclude the long-term use of MP29-02 in the treatment of allergic rhinitis.

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.

MP29-02 for the treatment of seasonal allergic rhinitis: a review of clinical pharmacology, efficacy and safety.

This review presents the pharmacology, clinical efficacy and safety of MP29-02 (Dymista®), a unique product for the treatment of allergic rhinitis. Allergic rhinitis is often thought of more as a nuisance than a meaningful medical condition, and the health impact of allergic rhinitis can easily be underestimated. As a result, allergic rhinitis can be undertreated, expectations for relief may not be met, and patients may be left dissatisfied and non-compliant with their medications. MP29-02 is the only currently available allergic rhinitis medication to provide potent early-phase histamine-receptor blocking and long-term anti-inflammatory effects in a single intranasal formulation and delivery system that represents an advance in the therapy of allergic rhinitis, in particular for patients with moderate-to-severe disease.

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.