Rhinitis, sinusitis, and upper airway disease
A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis

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Background

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Protocol

Individual results and a meta-analysis of 3 phase III, multicenter, randomized, double-blind, parallel-group trials (MP4002 [NCT00651118], MP4004 [NCT00740792], and MP4006 [NCT00883168]) were assessed in patients with moderate-to-severe SAR to determine the efficacy of MP29-02 compared with intranasal H1-antihistamine (azelastine), corticosteroid (FP), and placebo using the same formulation. Placebo spray comprised exactly the same vehicle/formulation as the active treatments without any active

Patients

Study completion rates were high (approximately 95%) and similar across studies and across treatment groups (see Table E2 in this article’s Online Repository at www.jacionline.org). Dropout rates were negligible (see Table E3 in this article’s Online Repository at www.jacionline.org). When data were pooled for meta-analysis, 848, 846, 847, and 857 patients received MP29-02, FP, azelastine, and placebo, respectively. The baseline characteristics of the 4 treatment groups were similar, both

Discussion

Before MP29-02, no clinical development program had demonstrated additional benefit over 2 currently recommended first-line AR therapies in patients with moderate-to-severe disease. In the present program MP29-02 demonstrated superior efficacy over intranasal FP and intranasal azelastine monotherapy in patients with AR in a set of 3 randomized, double-blind, placebo-controlled clinical studies with active controls by using the same device and formulation. This provides sound clinical evidence,

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    These studies were funded by Meda Pharmaceuticals, Inc, and were designed to be consistent with recommendations provided in the US Food and Drug Administration guidance document for clinical development of drug products for allergic rhinitis (Guidance for Industry, US Department of Health and Human Services, US Food and Drug Administration Center for Drug Evaluation and Research; April 2000).

    Disclosure of potential conflict of interest: W. Carr has consulted for and received research support from MEDA, Alcon, and Ista. J. Bernstein has received research support from Meda and Dynova; is on the Board of Directors and a Fellow of the American Association of Allergy, Asthma & Immunology (AAAAI); is a Fellow at the American College of Allergy, Asthma & Immunology (ACAAI); and is Chairman of the Allergists for Israel (AFI). P. Lieberman is an advisor for the Allergy Foundation of America and Baxter and has given lectures for MEDA, Genentech, Ista, and TEVA. E. Meltzer has received research support from Amgen, Apotex, HRA, MedImmune, Schering-Plough, Alcon, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Proctor & Gamble, Sunovion (Sepracor), and Teva; is a consultant and/or is on the advisory board for Alcon, AstraZeneca, Bausch & Lomb, Dey, Forest, Ista, Johnson & Johnson, Meda, Merck, ONO Pharma, OptiNose, Proctor & Gamble, Rady Children’s Hospital, Rigel, Sanofi-Aventis, Sepracor, Stallergenes, Teva, Alexa, Boehringer Ingelheim, Kalypsys, and Sunovion; is a speaker for the AAAAI, Alcon, Allergists for Israel, Dey, Florida Allergy Asthma Immunology Society, Ista, Sepracor, Teva, Merck, and Sunovion; and has provided expert designation in legal matters for Aventis Pharmaceuticals and Sanofi Aventis v. Barr Laboratories, Fexofenadine. D. Price has received consultancy and speaker fees from Merck, Mundipharma, Novartis, Medapharma, Kyorin, and TEVA; has received consultancy fees from GlaxoSmithKline, Almirall, and Chiesi; has received consultancy fees and grants from Pfizer, and AstraZeneca; has received consultancy and speakers’ fees and grants from Boehringer Ingelheim; has received speakers’ fees and grants from Aerocrine; has received grants from the UK National Health Service, Nycomed, and Medapharma; is director of Research in Real Life Ltd; is a guideline group member for Allergic Rhinitis and its Impact on Asthma and EPOS; is a research committee member for International Primary Care Respiratory Group; and has shares in AKL Ltd. J. Bousquet has received honoraria from Stallergenes, Actelion, Almirall, AstraZeneca, Chiese, GlaxoSmithKline, Merck, Novartis, OM Pharma, Sanofi, TEVA, and Uriach. The rest of the authors declare that they have no relevant conflicts of interest.

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