AZELASTINE/FLUTICASONE (AZE/FLU) Nasal Spray on Symptom Control, Nasal Mediators and Nasal Hyperresponsiveness in Allergic Rhinitis (AR)

Study Overview
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Brief Summary
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Comparative analysis of the efficacy of intranasal MP29-02 (a novel formulation of azelastine and FP) has already been conducted in patients with moderate-to-severe seasonal AR. The combination formulation appeared to be superior in these patients with better symptomatic relief. However, objective analysis of the effect of this treatment on nasal mediators and/or nasal hyperreactivity has not yet been performed and would help in understanding the additional benefit of the combination treatment over monotherapy with nasal corticosteroids.

Detailed Description
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Comparative analysis of the efficacy of intranasal MP29-02 (a novel formulation of azelastine and FP) has already been conducted in patients with moderate-to-severe seasonal AR. The combination formulation appeared to be superior in these patients with better symptomatic relief. However, objective analysis of the effect of this treatment on nasal mediators and/or nasal hyperreactivity has not yet been performed and would help in understanding the additional benefit of the combination treatment over monotherapy with nasal corticosteroids.

Official Title
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AZE/FLU Nasal Spray on Symptom Control, Nasal Mediators and Nasal Hyperresponsiveness in Allergic Rhinitis (AR)

Conditions
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Allergic Rhinitis, House Dust Mite Allergy

Intervention / Treatment
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* Drug: azelastine + fluticasone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with an ARIA-based diagnosis of persistent moderate/severe AR (≥ 2 nasal symptoms suggestive of allergic rhinitis and positive skin prick tests to house dust mite (HDM) (HAL Allergy, Leiden, The Netherlands) at screening. Patients with additional seasonal pollen allergies may be included providing that they are included outside their individual pollen season, and with VAS score for total nasal symptoms of more than 5 VAS for TNS of more than 5, and rT5SS of more than 8 at both screening and randomization Age > 18 and < 60 years Eosinophilia of more than 5% in nasal secretions at screening Nasal hyperreactivity (drop of PNIF >20 %) at randomization Possibility to give reliable information and written informed consent Exclusion Criteria: Any evidence of clinically relevant acute or chronic cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrine, metabolic, mental, neurological, or other disease at screening History of allergic reaction to fluticasone propionate, azelastine hydrochloride or one of the excipients (e.g. benzalkonium chloride, phenylethyl alcohol, microcrystalline cellulose) Patients with a change in vision or with a history of increased ocular pressure, glaucoma and/or cataracts Patients with tuberculosis, any type of untreated infection, or recent surgical operation or injury to the nose or mouth Patients on prolonged use of decongestive nose sprays, suffering from so-called rhinitis medicamentosa Patients using other nasal or oral medication affecting nasal function, like nasal corticosteroids, anticholinergics, cromoglycates, leukotriene antagonists, ACE inhibitors during the study or within the last 14 days before randomization; patients using oral corticosteroids during the last 30 days Patients using cytochrome P450 inhibitors (e.g. ritonavir) Nasal endoscopic evidence of rhinosinusitis with or without nasal polyposis (NP) or structural abnormalities such as clinically relevant septal deviation (septum reaching concha inferior or lateral nasal wall) or septal perforation at screening Patients on immunotherapy (IT) for HDM or with history of IT for HDM Patients with a psychiatric, addictive, or any disorder of which the investigators feel that this may compromise the ability to give truly informed consent for participation in this study or provide reliable information on the questionnaire Patients being enrolled in other clinical trials within the last 3 months Pregnancy or breastfeeding Malignancies or severe comorbidity Smoking Use of anticoagulation medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: azelastine + fluticasone<br>azelastine 137 µg + fluticasone 50 µg combined applied twice daily one puff in each nostril duration: 4 weeks | Drug: azelastine + fluticasone<br> <br> * Other names: dymista;|
| Placebo Comparator: placebo<br>twice daily one puff in each nostril duration: 4 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in expression of inflammatory mediators (Histamine / Substance P / IL-5 / EPO) | Change in expression of inflammatory mediators (Histamine / Substance P / interleukin 5 (IL-5) / EPO) at after 4 weeks of therapy with AZE/FP or placebo nasal spray. Unit of measurement: µg/ml | 4 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in PNIF values upon CDA exposure | Nasal hyperreactivity (NHR) can be assessed with peak nasal inspiratory flow (PNIF) measurement before and after cold dry air (CDA) provocation. Peak nasal inspiratory flow (PNIF) Peak nasal inspiratory flow evaluation is a physiologic measure of air flow through both nasal cavities during forced inspiration. The PNIF can be measured using a portable nasal inspiratory ﬂow meter and is expressed in liters per minute. Cold dry air (CDA) provocation CDA nasal provocation can be performed by delivering compressed dry air through a mask placed over nose and mouth of the patient, while breathing only through the nose. Patients will be exposed during 15 minutes. NHR is defined as a drop in PNIF larger than 20 % from baseline upon CDA challenge. The efficacy of MP29-02 treatment will be evaluated by measuring the change in PNIF values upon CDA exposure in both treatment arms. Unit of measurement of PNIF: L/min | 4 weeks treatment |