Official Title: “A Proof of Concept Study to Evaluate Comparative Efficacy of an Azelastine/Fluticasone Combination Nasal Spray vs. Twice the Dose of Fluticasone in Persistent Allergic Rhinitis”

The purpose of this study is to see how a combination spray of azelastine and fluticasone (antihistamine and steroid) compares with a steroid nasal spray (fluticasone) alone in allergic rhinitis i.e. does azelastine permit the use of lesser steroid dose (steroid sparing effect) to achieve the same benefit.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2011

Allergic rhinitis (AR) is a major chronic respiratory disease with a prevalence approaching nearly 25% in the worldwide population.Allergic Rhinitis is a common and relatively undiagnosed public health problem and has been reported as being one of the ten most common causes for outpatient attendances to the general practitioner. Long term untreated allergic rhinitis may lead on to asthma. When exposed to allergens (pollen, house dust mite etc) in the atmosphere, the mast cells in the nose burst and an inflammatory response is triggered and patients experience sneezing, itching, blocked nose and running. These allergens may be used as provocation agents to recreate the disease symptoms to confirm the diagnosis of which allergens one is allergic to. However, there is a risk of allergic reactions in doing so. Adenosine monophosphate (AMP)achieves the same goal by stimulating the mast cells and causing them to burst without actually the risks of allergen provocation tests. Such tests are now commonplace in research and clinical medicine. Nasal steroids are considered to be the most potent medications for allergic rhinitis, particularly nasal blockage. Nasal antihistamines are also available but they act mainly to limit nasal running, itching and sneezing and have lesser effect on blockage. The other advantage is that they act very quickly while steroids take at least 72 hours to begin acting and weeks to achieve maximal benefit. Finally, they are free of significant short and long term side effects. Having said that nasal steroids are very safe and unlike inhaled or oral steroids have not been shown to cause systemic side effects in adults. Therefore, it is interesting to see if a combination of an antihistamine and nasal steroid would add their good qualities mentioned above and by the act of reducing the dose of steroid reduce their side effects. To do this we will use nasal AMP challenge as an outcome measure as we have done research studies for over a decade with. We will look at noninvasive nasal airflow parameters, nasal nitric oxide levels, and for safety we will look at the overnight urinary cortisol and creatinine ratio which is the most sensitive and noninvasive test of urine to quantify how much steroid has been absorbed in the blood stream.

Intervention(s) in this Clinical Trial

• Drug: Azelastine , fluticasone
  • Azelastine Hydrochloride BP 0.10% w/v AND Fluticasone propionate BP 0.0357% w/v as combination 1 squirt in each nostril twice daily
• Drug: Fluticasone propionate
  • Fluticasone propionate 0.05% w/w 2 squirts in each nostril (50 μg per squirt)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Azelastine Fluticasone
• Active Comparator: Fluticasone propionate

Primary Measures

• Maximum percentage fall in PNIF after 400mg/ml of AMP nasal challenge between both groups.
  • Time Frame: 0, 2 weeks, 4 weeks, 6 weeks, 8 weeks
    Safety Issue?: No

Secondary Measures

• 60 minute recovery to AMP challenge
  • Time Frame: 0, 2 weeks, 4 weeks, 6 weeks, 8 weeks
    Safety Issue?: No
• Mini RQLQ
  • Time Frame: 0, 2 weeks, 4 weeks, 6 weeks, 8 weeks
    Safety Issue?: No
• Global visual analogue scale
  • Time Frame: 0, 2 weeks, 4 weeks, 6 weeks, 8 weeks
    Safety Issue?: No
• Nasal lavage for cytokines
  • Time Frame: 0, 2 weeks, 4 weeks, 6 weeks, 8 weeks
    Safety Issue?: No
• Overnight urinary cortisol creatinine ratio
  • Time Frame: 0, 2 weeks, 4 weeks, 6 weeks, 8 weeks
    Safety Issue?: Yes
• Domiciliary diary cards
  • Time Frame: 2 week treatment periods
    Safety Issue?: No

Inclusion Criteria:

• Male of Female aged 18‐65 years.
• Persistent allergic rhinitis with or without asthma.
• Atopy to at least one allergen on SPT.
• Ability to give a written informed consent.
• Ability and willingness to comply with the requirements of the protocol.

Exclusion Criteria:

• Recent respiratory tract/sinus infection within the last 2 months. .
• Pregnancy, planned pregnancy or lactation.
• Known or suspected hypersensitivity to any of the IMP's.
• Concomitant use of medicines (prescribed, OTC or herbal) like alpha blockers that may interfere with the trial.
• Nasal Polyposis grade 2+, Deviated nasal septum ≥ 50%
• The use of oral corticosteroids within the last 3 months.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Dundee

Overall Clinical Trial Officials and Contacts

Sriram Vaidyanathan, MBBS Principal Investigator University of Dundee  

Overall Contact: Sriram Vaidyanathan, MBBS +44 1382496355 s.vaidyanathan@dundee.ac.uk

Information obtained from ClinicalTrials.gov on February 04, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00845598

Study ID Number: VAI04

ClinicalTrials.gov Identifier: NCT00845598

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency