Research Article: A four-way, double-blind, randomized, placebo controlled study to determine the efficacy and speed of azelastine nasal spray, versus loratadine, and cetirizine in adult subjects with allergen-induced seasonal allergic rhinitis

Date Published: May 1, 2013

Publisher: BioMed Central

Author(s): Anne K Ellis, Yifei Zhu, Lisa M Steacy, Terry Walker, James H Day.


Azelastine has been shown to be effective against seasonal allergic rhinitis (SAR). The Environmental Exposure Unit (EEU) is a validated model of experimental SAR. The objective of this double-blind, four-way crossover study was to evaluate the onset of action of azelastine nasal spray, versus the oral antihistamines loratadine 10 mg and cetirizine 10 mg in the relief of the symptoms of SAR.

70 participants, aged 18-65, were randomized to receive azelastine nasal spray, cetirizine, loratadine, or placebo after controlled ragweed pollen exposure in the EEU. Symptoms were evaluated using the total nasal symptom score (TNSS). The primary efficacy parameter was the onset of action as measured by the change from baseline in TNSS.

Azelastine displayed a statistically significant improvement in TNSS compared with placebo at all time points from 15 minutes through 6 hours post dose. Azelastine, cetirizine, and loratadine reduced TNSS compared to placebo with an onset of action of 15 (p < 0.001), 60 (p = 0.015), and 75 (p = 0.034) minutes, respectively. The overall assessment of efficacy was rated as good or very good by 46% of the participants for azelastine, 51% of the participants for cetirizine, and 30% of the participants for loratadine compared to 18% of the participants for placebo. Azelastine’s onset of action for symptom relief was faster than that of cetirizine and loratadine. The overall participant satisfaction in treatment with azelastine is comparable to cetirizine and statistically superior to loratadine. These results suggest that azelastine may be preferential to oral antihistamines for the rapid relief of SAR symptoms.

Partial Text

Seasonal allergic rhinitis (SAR) is an inflammatory disease characterized by multiple symptoms including sneezing, rhinnorhea, nasal congestion, nasal and nasopharyngeal itching, and has associated ocular symptoms such as itchy, watery and red/burning eyes
[1]. Oral antihistamines are often the first line treatment administered for SAR
[2]. However, as SAR symptoms result from an interaction between inhaled allergens and IgE antibodies on mast cells located in the upper airway
[3], it may be possible to achieve faster symptom relief through direct local delivery of a medication to the nasal tissues.

A total of 70 participants were randomized and all participants took at least one dose of study drug and thus received at least one efficacy evaluation. All 70 participants were included in the ITT population; however 4 participants were excluded from the PP population for failing to complete all four dosing periods or for lacking the required symptom score. The demographic characteristics of study participants and the baseline symptom scores prior to dosing period 1 are summarized in Table 
3 and were similar among the four treatment sequences.

This study was designed to characterize the exact onset of action for allergic rhinitis symptom relief by azelastine (1 spray per nostril) compared to the onset of action of established oral antihistamines loratadine 10 mg and cetirizine 10 mg tablets.

To our knowledge, this is the first trial directly comparing the onset of action of azelastine, cetirizine, and loratadine for the treatment of SAR. The unique operational characteristics of the EEU facilitated this head-to-head comparison. This study supports the rapid onset of action of azelastine nasal spray to relieve SAR symptoms; more quickly than oral antihistamines. The faster onset combined with comparable levels of symptom relief suggest that azelastine could be used as a replacement for oral antihistamines in the management of SAR.

ITT: Intent to treat; PP: Per protocol; SAR: Seasonal allergic rhinitis; TNSS: Total nasal symptom score

Dr Ellis has received speaking honoraria from Pfizer, Merck and Sanofi, has served on an Advisory Board for Sanofi, and has received research grants from Circassia Ltd, Adiga Life Sciences, and GlaxoSmithKline in the last 12 months. All other authors declare that have no competing interests.

AKE was involved in drafting of the manuscript and critically revising its contents. YZ drafted the manuscript and assisted with subsequent revisions. LMS participated in subject recruitment and was a study coordinator for the study. TW ensured appropriate levels of ragweed pollen in EEU. JHD was involved in protocol revisions for the study and carried out the study for data procurement. All authors read and approved the final manuscript.

James H. Day: Post-humous.




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