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

Allergic Rhinitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02238353
• Other study ID #: azelastine/fluticasone AZE/FLU
• Status: Recruiting
• Phase: Phase 4
• First received: August 22, 2013
• Last updated: December 2, 2015
• Start date: October 2014
• Est. completion date: December 2015

Study information

• Verified date: December 2015
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Allergic Rhinitis
• House Dust Mite Allergy
• Rhinitis

Intervention

Drug:
• azelastine + fluticasone

• Placebo

Locations

Country	Name	City	State
Belgium	Uz Leuven Dienst Nko	Leuven	Vlaams Brabant

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	No
Other	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 ?ow 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	No
Other	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	No
Primary	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	No
Secondary	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 ?ow 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	No