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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo nasal spray that is similar to Dymista in all respects except the active ingredient |
|
| Fluticasone propionate | Experimental | Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista |
|
| Dymista (fluticasone/azelastine) | Experimental | Dymista is also provided as a nasal spray in bottles similar to the other two agents |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Patients will be treated by placebo |
|
|
| 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. |
| 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. |
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fuad M Baroody, MD | University of Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Chicago Medicine | Chicago | Illinois | 60637 | United States |
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cross-over study
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| ID | Title | Description |
|---|---|---|
| FG000 | Dymista/Placebo/Flonase | Randomized order of Dymista, then Placebo, then Flonase |
| FG001 | Dymista/Flonase/Placebo | Randomized order of Dymista, then Flonase, then Placebo |
| FG002 | Placebo/Dymista/Flonase | Randomized order of Placebo, then Dymista, then Flonase |
| FG003 | Placebo/Flonase/Dymista | Randomized order of Placebo, then Flonase, then Dymista |
| FG004 | Flonase/Dymista/Placebo | Randomized order of Flonase, then Dymista, then Placebo |
| FG005 | Flonase/Placebo/Dymista | Randomized order of Flonase, then Placebo, then Dymista |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
This is a cross-over study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dymista/Placebo/Flonase | Dymista: Fluticasone/Azelastine nasal spray Flonase: Fluticasone nasal spray Placebo: nasal spray without active ingredient |
| BG001 | Dymista/Flonase/Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Posted | Mean | Standard Error | ng/mL | 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks. |
|
with one month of patient study completion
does not differ
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo nasal spray that is similar to Dymista in all respects except the active ingredient Placebo: Patients will be treated by placebo 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 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Fuad Baroody, MD | University of Chicago | 773-702-4790 | fbaroody@surgery.bsd.uchicago.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 21, 2017 | Nov 30, 2020 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 8, 2017 | Nov 30, 2020 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D065631 | Rhinitis, Allergic |
| ID | Term |
|---|---|
| D012220 | Rhinitis |
| D009668 | Nose Diseases |
| D012140 | Respiratory Tract Diseases |
| D012130 | Respiratory Hypersensitivity |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| D000068298 | Fluticasone |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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| Fluticasone propionate | Drug | Patients will receive fluticasone nasal spray |
|
|
| Fluticasone/Azelastine nasal spray | Drug | Patients will receive Dymista nasal spray |
|
|
| Nasal Allergen Challenge | Procedure | 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 |
|
|
| 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. |
| Lost to Follow-up |
|
Dymista:
Fluticasone/Azelastine nasal spray
Flonase: Fluticasone nasal spray
Placebo: nasal spray without active ingredient
| BG002 | Placebo/Dymista/Flonase | Dymista: Fluticasone/Azelastine nasal spray Flonase: Fluticasone nasal spray Placebo: nasal spray without active ingredient |
| BG003 | Placebo/Flonase/Dymista | Dymista: Fluticasone/Azelastine nasal spray Flonase: Fluticasone nasal spray Placebo: nasal spray without active ingredient |
| BG004 | Flonase/Dymista/Placebo | Dymista: Fluticasone/Azelastine nasal spray Flonase: Fluticasone nasal spray Placebo: nasal spray without active ingredient |
| BG005 | Flonase/Placebo/Dymista | Dymista: Fluticasone/Azelastine nasal spray Flonase: Fluticasone nasal spray Placebo: nasal spray without active ingredient |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Fluticasone Propionate | Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista Fluticasone propionate: Patients will receive fluticasone nasal spray 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 |
| OG002 | Dymista (Fluticasone/Azelastine) | Dymista is also provided as a nasal spray in bottles similar to the other two agents Fluticasone/Azelastine nasal spray: Patients will receive Dymista nasal spray 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 |
|
|
|
| Secondary | 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). | Posted | Mean | Standard Error | Sneezes | 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks. |
|
|
|
|
| Other Pre-specified | 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. | Posted | Mean | Standard Error | score on a scale | 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks. |
|
|
|
|
| Other Pre-specified | 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). | There was one missing sample | Posted | Mean | Standard Error | ng/mL | 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks. |
|
|
|
|
| Other Pre-specified | 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). | due technical difficulty in the staining, no data is available. | Posted | 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks. |
|
|
| Other Pre-specified | 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). | there were three missing samples | Posted | Mean | Standard Error | ng/mL | 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks. |
|
|
|
|
| Other Pre-specified | 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). | Data was missing for 3 subjects | Posted | Mean | Standard Error | ng/ml | 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks. |
|
|
|
|
| Other Pre-specified | 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). | Posted | Mean | Standard Error | ng/mL | 3 rounds of 1 Nasal challenge every 3 days followed by 2 week washout periods in between. Total participation of 9 weeks. |
|
|
|
|
| 0 |
| 19 |
| 0 |
| 19 |
| 0 |
| 19 |
| EG001 | Fluticasone Propionate | Fluticasone propionate nasal spray provided in a bottle similar to placebo and dymista Fluticasone propionate: Patients will receive fluticasone nasal spray 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 | 0 | 19 | 0 | 19 | 0 | 19 |
| EG002 | Dymista (Fluticasone/Azelastine) | Dymista is also provided as a nasal spray in bottles similar to the other two agents Fluticasone/Azelastine nasal spray: Patients will receive Dymista nasal spray 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 | 0 | 19 | 0 | 19 | 0 | 19 |
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| D010038 |
| Otorhinolaryngologic Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D017670 |
| Sodium Compounds |
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
|
| day 3 |
|
| Wilcoxon (Mann-Whitney) |
| 0.02 |
| Median Difference (Net) |
| 24.5 |
| 2-Sided |
| Superiority |
| Wilcoxon (Mann-Whitney) | 0.003 | Median Difference (Net) | 4.5 | 2-Sided | Superiority |
| Wilcoxon (Mann-Whitney) | 0.53 | Median Difference (Net) | 48.5 | 2-Sided | Superiority |
|
| day 3 |
|
|
| day 3 |
|