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

Evaluating Factors Involved in Dymista's Superior Clinical Efficacy to Fluticasone Propionate in the Treatment of Seasonal Allergic Rhinitis

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.

Study Overview

• Status: Completed
• Conditions: Allergic Rhinitis
• Intervention / Treatment: Drug: Placebo; Procedure: Nasal Allergen Challenge; Drug: Fluticasone propionate; Drug: Fluticasone/Azelastine nasal spray

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo nasal spray that is similar to Dymista in all respects except the active ingredient	Drug: Placebo; Patients will be treated by placebo; Other Names: saline; Procedure: Nasal Allergen Challenge; All subjects will receive a nasal challenge with allergen to mimick an allergic response and allow the investigation of the different drug effects on that response. Allergen extracts will be used as sprays into the nasal cavity. The extracts are approved by FDA for skin testing or desensitization therapy and an IND was obtained to allow intranasal administration; Other Names: Nasal provocation
Experimental: Fluticasone propionate; Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista	Procedure: Nasal Allergen Challenge; All subjects will receive a nasal challenge with allergen to mimick an allergic response and allow the investigation of the different drug effects on that response. Allergen extracts will be used as sprays into the nasal cavity. The extracts are approved by FDA for skin testing or desensitization therapy and an IND was obtained to allow intranasal administration; Other Names: Nasal provocation; Drug: Fluticasone propionate; Patients will receive fluticasone nasal spray; Other Names: Flonase
Experimental: Dymista (fluticasone/azelastine); Dymista is also provided as a nasal spray in bottles similar to the other two agents	Procedure: Nasal Allergen Challenge; All subjects will receive a nasal challenge with allergen to mimick an allergic response and allow the investigation of the different drug effects on that response. Allergen extracts will be used as sprays into the nasal cavity. The extracts are approved by FDA for skin testing or desensitization therapy and an IND was obtained to allow intranasal administration; Other Names: Nasal provocation; Drug: Fluticasone/Azelastine nasal spray; Patients will receive Dymista nasal spray; Other Names: Dymista

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline Response in Albumin Levels in Nasal Lavage Following Each Challenge	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).	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sneezes After Allergen Challenge	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).	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Nasal Symptom Score	Total nasal symptom Score = Sum of itchy, runny, sneezing, and congestion scores, each on scale 0-3 (0=no symptoms, 1=mild symptoms, 2=moderate symptoms, 3=severe symptoms). Thus, maximum=12, minimum=0, and higher score represents worse outcome. Measured in the 10 minute period after allergen challenge and normalized against symptoms experienced after sham challenge.	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
Change From Baseline Response in Lactoferrin Levels in Nasal Lavage Following Each Challenge	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 (lactoferrin amount in lavage after 1st allergen exposure - amount after sham) + (amount in lavage after 2nd exposure - sham amount).	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
Eosinophils	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 (number of eosinophils in lavage after 1st allergen exposure - number after sham) + (number in lavage after 2nd exposure - sham number).	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
Histamine	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 (histamine amount in lavage after 1st allergen exposure - amount after sham) + (amount in lavage after 2nd exposure - sham amount).	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
Tryptase	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 (tryptase amount in lavage after 1st allergen exposure - amount after sham) + (amount in lavage after 2nd exposure - sham amount).	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.
Eosinophil Cationic Protein (ECP)	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 (ECP amount in lavage after 1st allergen exposure - amount after sham) + (amount in lavage after 2nd exposure - sham amount).	3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks.

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Fuad M Baroody, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: March 18, 2015
• First Submitted That Met QC Criteria: March 24, 2015
• First Posted (Estimated): March 30, 2015

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H1 Antagonists, Non-Sedating; Lipoxygenase Inhibitors; Fluticasone; Xhance; Azelastine
• Other Study ID Numbers: IRB14-1199