mp29-02 and azelastine

Effective pharmacologic treatment exists for most patients suffering from allergic rhinitis (AR). However, both in clinical trials and in real-life studies, many patients are dissatisfied with treatment. Physicians often use multiple therapies, in an attempt to improve symptom control, often with limited evidence of success. Novel treatment options are needed and must consider unmet medical needs.. This article reviews the clinical data for a new AR treatment. MP29-02 (Dymista®, Meda, Solna, Sweden) contains azelastine hydrochloride (AZE) and fluticasone propionate (FP), in a novel formulation and delivered in an improved device as a single nasal spray. It has shown superior efficacy in AR patients than either commercially available AZE or FP monotherapy for both nasal and ocular symptom relief, regardless of disease severity. MP29-02 also provided more effective and rapid symptom relief than either AZE or FP monotherapy delivered in the MP29-02 formulation and device. However, the effect was less than that observed versus commercial comparators, suggesting the impact of formulation and device on clinical efficacy.. MP29-02 simplifies AR management, surpassing the efficacy of gold standard treatment, intranasal corticosteroids (INS), for the first time. It is indicated for the treatment of moderate-to-severe seasonal allergic rhinitis and perennial allergic rhinitis when monotherapy with either intranasal antihistamine or INS is NOT considered sufficient. Most patients present with moderate/severe disease, with evidence of current or previous treatment insufficiency. MP29-02 should be the treatment of choice for these patients.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Drug Combinations; Humans; Phthalazines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

It is unclear what constitutes a clinically meaningful response for allergic rhinitis (AR) outcomes. The objectives of these post hoc analyses were (1) to define a clinically meaningful response using novel efficacy analyses (including a responder analysis), and (2) to compare the efficacy of MP29-02 [a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP)] with commercially available FP, AZE and placebo in seasonal AR (SAR) patients, using these novel analyses.. 610 moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Change from baseline in the reflective total nasal symptom score (rTNSS) over 14 days was the primary outcome. Post hoc endpoints included the sum of nasal and ocular symptoms (rT7SS), efficacy by disease severity and by predominant nasal symptom, and a set of responder analyses.. MP29-02 most effectively reduced rT7SS (relative greater improvement: 52% to FP; 56% to AZE) and both nasal and ocular symptoms irrespective of severity. More MP29-02 patients achieved a ≥30, ≥50, ≥60, ≥75 and ≥90% rTNSS reduction, which occurred days faster than with either active comparator; MP29-02 alone was superior to placebo at the ≥60% (or higher) threshold. One in 2 MP29-02 patients achieved a ≥50% rTNSS reduction and 1 in 6 achieved complete/near-to-complete response. Only MP29-02 was consistently superior to placebo for all patients, whatever their predominant symptom.. MP29-02 provided faster and more complete symptom control than first-line therapies. It was consistently superior irrespective of severity, response criteria or patient-type, and may be considered the drug of choice for moderate-to-severe AR. These measures define a new standard for assessing relevance in AR.

Topics: Adult; Androstadienes; Anti-Allergic Agents; Cedrus; Disease Progression; Drug Combinations; Female; Fluticasone; Follow-Up Studies; Humans; Male; Middle Aged; Nasal Obstruction; Phthalazines; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Treatment Outcome; Young Adult

• The topical second generation anti-histamine azelastine hydrochloride (AZE) and the potent corticosteroid fluticasone propionate (FP) are well established first-line treatments in allergic rhinitis (AR). • MP29-02, a novel intranasal AZE and FP formulation, has been shown to control AR symptoms faster and better than standard intranasal AZE or FP. • The systemic bioavailabilities of marketed AZE and FP nasal spray products have been established at about 40% and 1% only, respectively. • For new combination medicinal products such as MP29-02, the determination of possible pharmacokinetic (PK) drug-drug interactions between both active components and formulation-based bioavailability alterations is essential.. • This paper provides for the first time information on potential drug-drug interactions, AZE and FP bioavailability and disposition characteristics of each component administered by the novel nasal spray formulation MP29-02. • The studies employed highly sensitive FP and AZE LC-MS/MS assays and could therefore be conducted with recommended therapeutic doses, thereby circumventing previously recognized draw-backs that required nasal bioavailability studies to be conducted using supra-therapeutic doses. • No significant PK drug-drug interaction between the active components AZE and FP was noted for MP29-02. • AZE bioavailabilty was equivalent when MP29-02 data were compared with MP29-02-AZE-mono and Astelin®. • Increased FP exposure was observed with MP29-02-based products compared with FP-BI. FP serum concentrations were generally very low with all investigational products suggesting no clinically meaningful pharmacodynamic differences in terms of systemic safety.. To determine azelastine hydrochloride (AZE) and fluticasone propionate (FP) bioavailabilities of the novel nasal spray combination product MP 29-02, compared with MP29-02-based products containing only AZE (MP29-02-AZE-mono), FP (MP29-02-FP-mono), marketed AZE and FP single entity products (Astelin® and FP Boehringer-Ingelheim; FP-BI).. Two randomized, three period, six sequence, three treatment crossover studies were conducted in healthy subjects. Study 1 administered 200 µg FP as MP29-02, MP29-02-FP-mono or FP-BI. Study 2 administered 548 µg AZE as MP29-02, MP29-02-AZE-mono or Astelin®. Each dose consisted of two sprays/nostril. Serum FP and plasma AZE were followed over 24 (FP) and 120 h (AZE) and quantified by LC-MS/MS. Peak (C(max) ) and total exposures AUC(0,t(last) ) were compared between the treatments by anova.. Study 1: Average FP C(max) was very low with all products (≤ 10 pg ml(-1) ). FP AUC(0,t(last) ) point estimates (90% CIs) for MP29-02 : MP29-02-FP-mono and MP29-02 : FP-BI ratios (%) were 93.6 (83.6, 104.7) and 161.1 (137.1, 189.3). Corresponding ratios for C(max) were 91.0 (82.5, 100.4) and 157.4 (132.5, 187.1). Study 2: AZE AUC(0,t(last) ) point estimates (90% CIs) for MP29-02 : MP29-02-AZE-mono and MP29-02 : Astelin® ratios (%) were 98.8 (91.0, 107.4) and 105.5 (95.6, 116.4). Corresponding outcomes for C(max) were 102.7 (92.1, 114.4) and 107.3 (92.6, 124.3).. No interactions of AZE and FP were found with the MP29-02 formulation. Azelastine bioavailability was similar for MP29-02 and Astelin®. Maximum and total FP exposure was higher for MP29-02-based products compared with FP-BI. FP concentrations were generally very low with all investigational products and did not suggest clinically meaningful differences concerning systemic safety.

Topics: Administration, Intranasal; Adolescent; Adult; Androstadienes; Anti-Allergic Agents; Biological Availability; Chromatography, High Pressure Liquid; Drug Combinations; Drug Delivery Systems; Drug Interactions; Female; Fluticasone; Humans; Male; Middle Aged; Nasal Sprays; Phthalazines; Rhinitis, Allergic, Seasonal; Tandem Mass Spectrometry; Young Adult

Moderate-to-severe allergic rhinitis (AR) is a challenge to treat, with many patients using multiple therapies and achieving limited symptom control. More effective therapies must be developed and tested in well-controlled, randomized, prospective studies with a direct comparison to current standards.. The aim of these studies was to investigate the efficacy of MP29-02 (a novel formulation of azelastine and fluticasone propionate [FP]) in patients with moderate-to-severe seasonal allergic rhinitis (SAR) and to compare its efficacy with 2 first-line therapies (ie, intranasal azelastine and intranasal FP) in this population.. Three thousand three hundred ninety-eight patients (≥12 years old) with moderate-to-severe SAR were enrolled into 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group trials (MP4002 [NCT00651118], MP4004 [NCT00740792], and MP4006 [NCT00883168]). Each trial was conducted for 14 days during different allergy seasons. The primary efficacy variable was the sum of the morning and evening change from baseline in reflective total nasal symptom score (range, 0-24) over the treatment period. Outcomes for the meta-analysis included efficacy according to disease severity and time to response in relevant responder criteria.. In the meta-analysis MP29-02 reduced the mean reflective total nasal symptom score from baseline (-5.7 [SD, 5.3]) more than FP (-5.1 [SD, 4.9], P < .001), azelastine (-4.4 [SD, 4.8], P < .001), or placebo (-3.0 [SD, 4.2], P < .001). This benefit was observed from the first day of assessment, with improvement in each individual nasal symptom, even in the patients with the most severe disease. MP29-02 achieved response consistently days earlier and showed greater efficacy in patients with moderate-to-severe rhinitis than FP and azelastine.. MP29-02 represents a novel therapy that demonstrated superiority to 2 first-line therapies for AR. Patients with moderate-to-severe SAR achieved better control, and their symptoms were controlled earlier with MP29-02 than with recommended medications according to guidelines.

Topics: Administration, Intranasal; Adult; Androstadienes; Disease Progression; Drug Combinations; Female; Fluticasone; Guidelines as Topic; Humans; Male; Middle Aged; Nasal Obstruction; Phthalazines; Rhinitis, Allergic, Seasonal; Seasons; Severity of Illness Index; Young Adult

MP 29-02, which contains fluticasone propionate and azelastine hydrochloride, is used as a topical nasal application for the treatment of seasonal and perennial allergic rhinitis. Although a multitude of data is available on the clinical symptom reduction and treatment safety of MP 29-02, the effect of MP 29-02 on ciliary beat frequency (CBF) has not been evaluated thus far.. MP 29-02-containing solution was applied at concentrations of 2.5, 5, 10, and 20% to 14 healthy subjects, and nasal ciliated epithelial cells were then visualized using a phase-contrast microscope. CBF was measured after the application of MP 29-02. For a comparison, fluticasone propionate was used. CBF measurements were then performed for 15 min at 22 °C. Ringer's solution was applied as a negative control.. MP 29-02 significantly reduced CBF at all the tested concentrations compared with that of the control group within the observation time. At a 2.5% concentration, MP 29-02 significantly reduced CBF from 6.81 Hz (SD ± 1.35 Hz) at baseline to 4.88 Hz (SD ± 1.52 Hz, p < 0.001) after 15 min. In contrast, for fluticasone propionate, a significant reduction was observed only with the 20% concentration after 5, 10, and 15 min.. MP 29-09 significantly reduced CB, with an almost linear relationship between the MP 29-09 concentration and reduction in CBF. For fluticasone propionate, a significant reduction of CBF was observed only at the highest analyzed concentration. The findings have implications for the long-term use of the MP 29-02. Yet, further clinical studies are needed to confirm these results in vivo, especially in patients with seasonal or perennial allergic rhinits.

Topics: Administration, Intranasal; Adult; Androstadienes; Drug Combinations; Epithelial Cells; Female; Fluticasone; Humans; In Vitro Techniques; Male; Middle Aged; Nasal Mucosa; Phthalazines; Rhinitis, Allergic, Perennial