This study confirms the usefulness of azelastine nasal spray for the symptomatic treatment of seasonal allergic rhinitis. Concerning onset of action in particular, the results favour the topical treatment over systemic therapy.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • 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. WHAT THIS STUDY ADDS • 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. AIM(S) 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). METHODS 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 (Cmax) and total exposures AUC(0,tlast) were compared between the treatments by anova. RESULTS Study 1: Average FP Cmax was very low with all products (≤10 pg ml−1). FP AUC(0,tlast) 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 Cmax were 91.0 (82.5, 100.4) and 157.4 (132.5, 187.1). Study 2: AZE AUC(0,tlast) 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,...

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The efficacy and tolerability of intranasal azelastine (0.14 mg/nostril twice daily) and oral terfenadine (60 mg twice daily) were compared under double-blind conditions in two 6-week, multicenter, parallel-group studies, including 167 patients suffering from seasonal and 52 patients suffering from perennial allergic rhinitis. In both studies, patients were symptomatic on entry and showed significant improvement on both treatments within the first 8 d of therapy, showing little further improvement with continued treatment. Symptoms most pronounced on entry--nasal itching, rhinorrhea, sneezing, and nasal obstruction--responded best to treatment (response rates 80-90%). Objective signs such as mucosal swelling and conjunctivitis improved in a manner parallel to symptoms. In perennial rhinitis, azelastine showed a trend to a superior relief of rhinorrhea and nasal obstruction, whereas terfenadine showed a trend toward better control of sneezing and nasal itchiness. No clinically relevant or statistically significant differences between treatments could be identified. The incidence of adverse effects of possible causal relationship to therapy was low. The most frequent effects in azelastine-treated patients were related to application site disorders, e.g., nasal irritation. Results indicate that with the dose used azelastine nasal spray is an effective treatment for both seasonal and perennial allergic rhinitis.

Loteprednol 400 microg once daily is superior to placebo and the only effective dose tested in improving nasal symptoms and objective parameters in patients with SAR.