Factors Involved in Dymista's Superior Clinical Efficacy in the Treatment of Seasonal Allergic Rhinitis

The University of Chicago

Status and phase: Completed; Phase 4

Conditions: Allergic Rhinitis

Treatments: Drug: Placebo; Procedure: Nasal Allergen Challenge; Drug: Fluticasone propionate; Drug: Fluticasone/Azelastine nasal spray

Study type: Interventional

Funder types: Other

Identifiers

NCT02402465

IRB14-1199

Details and patient eligibility

About

Dymista, a combined product containing the antihistamine azelastine and the intranasal steroid fluticasone, provides superior clinical efficacy to both fluticasone propionate and azelastine hydrochloride in the treatment of seasonal allergic rhinitis. The superiority of efficacy not only occurs at the initiation of treatment, but persists for its duration. The mechanism underlying the superior efficacy of Dymista is not known. This trial focuses on examining the effects of Dymista on the dynamics of the allergic response in man using nasal provocation with antigen. The investigators will study the relationship between symptoms, physiology, cells and mediators.

Full description

The main hypothesis for the trial is that Dymista affects multiple phases of the allergic response, which in sum are greater than the effects of fluticasone propionate or azelastine hydrochloride alone.

Our objectives for this study are to demonstrate:

1. that the induction of allergic inflammation by nasal provocation with antigen causes a cellular infiltration, with subsequent release of inflammatory biomarkers that cause augmented responses to subsequent exposure to antigens.
2. that fluticasone prevents allergic inflammation from developing after antigen challenge and subsequently prevents the augmentation of the nasal response to nasal challenge with antigen.
3. that the azelastine in Dymista reduces the effects of released histamine

To address these hypotheses we will perform a 3-way, randomized, placebo-controlled, and crossover trial. We will recruit 20 asymptomatic seasonal allergic rhinitis patients outside of the relevant season. The subjects will receive placebo, fluticasone propionate and Dymista. The nasal provocations will be separated by 2 weeks. Treatment will begin 15 minutes before nasal provocation with ragweed or grass antigen and the treatment will continue twice a day for 3 days. Nasal provocation will occur daily for three days to evaluate for priming (increased sensitization with repeated antigen exposure, which mimics seasonal disease where antigen exposure occurs in the setting of continued allergic inflammation). For outcome measures, we will monitor both nasal symptoms after nasal provocation as well as collect nasal lavage to evaluate effects on eosinophils and biomarkers of the immune response. In the nasal lavage, we will quantify the number of eosinophils (a marker of cellular recruitment) and measure the levels of histamine (a marker of basophil and mast cell activation), tryptase (a marker of mast cell activation), albumin (a marker of vascular permeability), lactoferrin (a marker of glandular activation) and ECP (a marker of eosinophil activation). Thus we expect to generate information on both clinical effects and physiologic differences between the treatments.

Enrollment: 22 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Males and females between 18 and 55 years of age.
2. History of grass and/or ragweed allergic rhinitis.
3. Positive skin test to grass and/or ragweed antigen.
4. Positive response to screening nasal challenge.
5. Off all anti-allergic medications for a minimum of 2 weeks.

Exclusion criteria

1. Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease.
2. Pregnant or lactating women.
3. Upper respiratory infection within 14 days of study start.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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22 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo nasal spray that is similar to Dymista in all respects except the active ingredient

Treatment:

Procedure: Nasal Allergen Challenge

Drug: Placebo

Fluticasone propionate

Experimental group

Description:

Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista

Treatment:

Procedure: Nasal Allergen Challenge

Drug: Fluticasone propionate

Dymista (fluticasone/azelastine)

Experimental group

Description:

Dymista is also provided as a nasal spray in bottles similar to the other two agents

Treatment:

Procedure: Nasal Allergen Challenge

Drug: Fluticasone/Azelastine nasal spray