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

Phase 4

Completed

• Conditions: Allergic Rhinitis
• Interventions: Drug: Fluticasone propionate; Drug: Fluticasone/Azelastine nasal spray; Drug: Placebo; Procedure: Nasal Allergen Challenge

• Registration Number: NCT02402465
• Lead Sponsor: University of Chicago

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-03-18
• Study First Submitted QC: 2015-03-24
• Study First Posted: 2015-03-30
• Primary Completion: 2018-03
• Study Completion: 2020-02
• Results First Submitted: 2021-12-20
• Status Verified: 2024-02
• Results First Submitted QC: 2024-10-14
• Last Update Submitted: 2024-10-14
• Results First Posted: 2024-10-17
• Last Update Posted: 2024-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Fluticasone propionate	Fluticasone propionate	Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista
Fluticasone propionate	Nasal Allergen Challenge	Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista
Dymista (fluticasone/azelastine)	Fluticasone/Azelastine nasal spray	Dymista is also provided as a nasal spray in bottles similar to the other two agents
Dymista (fluticasone/azelastine)	Nasal Allergen Challenge	Dymista is also provided as a nasal spray in bottles similar to the other two agents
Placebo	Placebo	Placebo nasal spray that is similar to Dymista in all respects except the active ingredient
Placebo	Nasal Allergen Challenge	Placebo nasal spray that is similar to Dymista in all respects except the active ingredient

Primary Outcome Measures

Name	Time	Method
Change From Baseline Response in Albumin Levels in Nasal Lavage Following Each Challenge	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.	Our procedure used a diluent (sham) challenge followed by 2 allergen challenges where lavages are collected 10 minutes after each of these challenges. The final value is (albumin amount in lavage after 1st allergen exposure - amount after sham) + (amount in lavage after 2nd exposure - sham amount).

Secondary Outcome Measures

Name	Time	Method
Sneezes After Allergen Challenge	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.	Our procedure used a diluent (sham) challenge followed by 2 allergen challenges. The final value is (the number of sneezes after 1st allergen exposure - number after sham) + (number of sneezes after 2nd exposure - sham amount).

Trial Locations

Locations (1)

The University of Chicago Medicine; 🇺🇸 Chicago, Illinois, United States