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: Unknown
• 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 (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fuad M Baroody, MD; Phone Number: 773-702-4790; Email: fbaroody@surgery.bsd.uchicago.edu
• Study Contact Backup: Name: Debbie Hawes; Phone Number: 773-702-4790; Email: dhawes@surgery.bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago Medicine
      • Contact: Fuad M Baroody, MD; Phone Number: 773-702-4790; Email: fbaroody@surgery.bsd.uchicago.edu
      • Contact: Debbie Hawes; Phone Number: 773-702-4790; Email: dhawes@surgery.bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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; 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
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; Drug: Fluticasone propionate; Patients will receive fluticasone nasal spray
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; 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
Albumin level in nasal lavage	We will calculate the total change of albumin levels after the allergen challenges and subtract the diluent (sham) response for a single value that will reflect the increase in vascular permeability after allergen challenges on the first day after treatment with the 3 different agents. This will be compared between therapies	Change in Albumin level after the first nasal challenge on each treatment arm. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and lavages are collected 10 minutes after each of these challenges

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sneezes after allergen challenge	We will evaluate the effects of the different interventions on the number of sneezes after allergen challenges	Number of sneezes after allergen challenges. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and sneezes are counted in a 10 minute period after each of the challenges

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Nasal Symptom Score	We will evaluate the total nasal symptoms (sum of itchy, runny, sneezing, and congestion scores, filled on a scale from 0-3) after allergen challenge and evaluate the effect of the interventions on these symptom scores.	Total nasal symptoms after allergen challenge. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and Total nasal symptom score is recorded for the 10 minute period after each of the challenges
Lactoferrin	We will evaluate the effects of the different interventions on the levels of lactoferrin in nasal lavages after allergen challenges	Lactoferrin levels in nasal lavages after allergen challenges. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and lavages are collected 10 minutes after each of these challenges
Eosinophils	We will count number of eosinophils in nasal lavages at the beginning of each challenge and evaluate the effects of the different treatments	Number of eosinophils in the first nasal lavage of the challenge. There will be 3 consecutive challenges separated by 24 hrs and eosinophils will be counted in the first lavage of each challenge
Histamine	We will evaluate the effects of the different interventions on the levels of histamine in nasal lavages after allergen challenges	Histamine levels in nasal lavages after allergen challenges. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and lavages are collected 10 minutes after each of these challenges
Tryptase	We will evaluate the effects of the different interventions on the levels of tryptase in nasal lavages after allergen challenges	Tryptase levels in nasal lavages after allergen challenges. The nasal challenge consists of a diluent challenge followed by 2 allergen challenges and lavages are collected 10 minutes after each of these challenges
Eosinophil cationic protein (ECP)	We will measure levels of ECP in nasal lavages at the beginning of each challenge and evaluate the effects of the different treatments	Levels of ECP in the first nasal lavage of the challenge.There will be 3 consecutive challenges separated by 24 hrs and ECP will be measured in the first lavage of each challenge

Collaborators and Investigators

• Sponsor: University of Chicago

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimate): July 20, 2016
• Last Update Submitted That Met QC Criteria: July 19, 2016
• Last Verified: July 1, 2016

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: 14-1199