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

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

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.

Study Overview

• Status: Unknown
• Conditions: Allergic Rhinitis; House Dust Mite Allergy
• Intervention / Treatment: Drug: Placebo; Drug: azelastine + fluticasone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • Recruiting
      • Uz Leuven Dienst Nko
      • Contact: emily dekimpe, Msc; Email: emily.dekimpe@uzleuven.be
      • Principal Investigator: peters hellings, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. VAS for TNS of more than 5, and rT5SS of more than 8 at both screening and randomization
3. Age > 18 and < 60 years
4. Eosinophilia of more than 5% in nasal secretions at screening
5. Nasal hyperreactivity (drop of PNIF >20 %) at randomization
6. Possibility to give reliable information and written informed consent

Exclusion Criteria:

1. Any evidence of clinically relevant acute or chronic cardiovascular, pulmonary, hepatic, renal, gastrointestinal, haematological, endocrine, metabolic, mental, neurological, or other disease at screening
2. History of allergic reaction to fluticasone propionate, azelastine hydrochloride or one of the excipients (e.g. benzalkonium chloride, phenylethyl alcohol, microcrystalline cellulose)
3. Patients with a change in vision or with a history of increased ocular pressure, glaucoma and/or cataracts
4. Patients with tuberculosis, any type of untreated infection, or recent surgical operation or injury to the nose or mouth
5. Patients on prolonged use of decongestive nose sprays, suffering from so-called rhinitis medicamentosa
6. 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
7. Patients using cytochrome P450 inhibitors (e.g. ritonavir)
8. 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
9. Patients on immunotherapy (IT) for HDM or with history of IT for HDM
10. 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
11. Patients being enrolled in other clinical trials within the last 3 months
12. Pregnancy or breastfeeding
13. Malignancies or severe comorbidity
14. Smoking
15. Use of anticoagulation medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in assessment of visual analogue scale (VAS) for total nasal symptom (TNS) and individual nasal symptoms, reflective total of 5 symptom scores (rT5SS) and Allergic Rhinitis Control Test (ARCT)	A Visual Analogue Scale (VAS) is a measurement of patient's subjective evaluation of symptom severity. Patients will score the severity of their total nasal symptoms (TNS) on a scale, as well as each individual nasal symptom (rhinorrhea, pruritis, sneezing, nasal obstruction), with 0 meaning no symptoms and 10 meaning the worst symptoms. The cut off value of 5/10 is to distinguish between controlled and uncontrolled AR. Patients will score their reflective nasal and ocular symptoms on a 4-point scale from absent (0), mild (1), moderate (2) to severe (3)). Minimum score: 0/15 as having no trouble with any of the symptoms; and maximum score: 15/15 as having maximum trouble with all the symptoms The Allergic Rhinitis Control Test (ARCT): Patients score the five questions from 1 (always troublesome) to 5 (never troublesome). Minimum score: 5/25 ; maximum score: 25/25. A score from 5/25 to 20/25 is assumed not controlled AR; a score higher then 20/25 is assumed controlled.	1 week after treatment
Effects of therapy with AZE/FP or placebo on nasal inflammatory mediators (Histamine / Substance P (SP) / IL-5 / EPO)	Change in expression of inflammatory mediators (Histamine / Substance P / IL-5 / EPO) at after 1 week of therapy with AZE/FP or placebo nasal spray. Unit of measurement: µg/ml	one week after treatment
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	1 week of treatment
change in assessment of visual analogue scale (VAS) for total nasal symptom (TNS) and individual nasal symptoms, rT5SS and Allergic Rhinitis Control Test (ARCT)	A Visual Analogue Scale (VAS) is a measurement of patient's subjective evaluation of symptom severity. Patients will score the severity of their total nasal symptoms (TNS) on a scale, as well as each individual nasal symptom (rhinorrhea, pruritis, sneezing, nasal obstruction), with 0 meaning no symptoms and 10 meaning the worst symptoms. The cut off value of 5/10 is to distinguish between controlled and uncontrolled AR. Patients will score their reflective nasal and ocular symptoms on a 4-point scale from absent (0), mild (1), moderate (2) to severe (3)). Minimum score: 0/15 as having no trouble with any of the symptoms; and maximum score: 15/15 as having maximum trouble with all the symptoms The Allergic Rhinitis Control Test (ARCT): Patients score the five questions from 1 (always troublesome) to 5 (never troublesome). Minimum score: 5/25 ; maximum score: 25/25. A score from 5/25 to 20/25 is assumed not controlled AR; a score higher then 20/25 is assumed controlled.	4 weeks after treatment

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: August 22, 2013
• First Submitted That Met QC Criteria: September 9, 2014
• First Posted (Estimate): September 12, 2014

Study Record Updates

• Last Update Posted (Estimate): December 3, 2015
• Last Update Submitted That Met QC Criteria: December 2, 2015
• Last Verified: December 1, 2015

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; 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; Azelastine
• Other Study ID Numbers: azelastine/fluticasone AZE/FLU