NoAL (HPMC) in Combination With Oxymetazoline in Patients With Allergic Rhinitis

Study Overview
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Brief Summary
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Allergic rhinitis is treated with a variety of systemic and locally applied drugs. The effectiveness of the intranasally applied formulations is diminished by the cleaning mechanisms of the nose, rhinorrhea in particular. Slowing down of the clearance of the nasal mucosa and prolonging the contact time of locally applied drugs with the nasal mucosa would improve their efficacy. One method is creating dosage forms containing mucoadhesive polymers. We have demonstrated that a mucoadhesive solution containing HPMC enhances the clinical efficacy of oxymetazoline. However, the industrial development of fixed combinations of pharmaceutical compound and mucoadhesive carrier requires substantial investments, escalating manifold if different pharmaceutical compounds have to be rendered mucoadhesive. NoAl is a cellulose derivative powder, which forms a gel layer on contact with the mucosal surface of the nose blocking the contact of the pollen grains with the nasal mucosa in seasonal allergic rhinitis. However, there is another potential benefit of applying NoAl (HPMC) along with other commercially available drugs for local treatment of rhinitis, as the formation of a gel layer can substantially delay their clearance from the nose and thus increase their effectiveness. This hypothesis needs to be substantiated clinically.

Detailed Description
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The main objective of the trial is to test the synergy between HPMC and oxymetazoline (both applied nasally) on the increase of peak nasal inspiratory flow in patients suffering from moderately severe / severe persistent allergic rhinitis. The design of the trial is parallel-groups, double blind, randomized, placebo controlled, single centre study. Forty patients are randomly assigned to receive either oxymetazoline followed by HPMC (Group A) or oxymetazoline followed by placebo (Group B). Each patient is followed up for 15 days. Day 1 is the screening and inclusion visit. Data will then be collected on day 8 & 15. Patients will fill in diaries their everyday symptoms, adverse events and applied medications.

Official Title
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Stage 2, Double-blind, Randomized, Parallel Groups, One Centre Study in Patients With Allergic Rhinitis Treated With Nasal Oxymetazoline in Combination With Nasal Hydroxyl-propyl-methyl Cellulose (HPMC) or Placebo

Conditions
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Allergic Rhinitis

Intervention / Treatment
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* Drug: Oxymetazoline
* Other: Hydroxyl-propyl-methyl cellulose powder
* Other: Placebo (lactose powder)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients Age ≥ 18 and ≤ 50 years Moderately severe / severe persistent allergic rhinitis Positive skin prick test for perennial aero-allergens Active symptoms with prominent congestion at the time of inclusion Exclusion Criteria: Subjects with pollen sensitization during the respective pollen season Subjects with arterial hypertension, arrhythmia or evidence of heart ischemia Subjects with other serious chronic comorbidities and bad therapeutic control Subjects with nasal polyposis Flu-like episode during the past 30 days Subjects unable to give informed consent Subjects with any of the contra-indications of oxymetazoline or NoAL Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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 |
| --- | --- |
| Active Comparator: Group A<br>One puff of oxymetazoline immediately followed by one puff of hydroxyl-propyl-methyl cellulose powder, morning & evening, for 8 days. | Drug: Oxymetazoline<br>* Intranasal application<br>* Other names: Afrin;Other: Hydroxyl-propyl-methyl cellulose powder<br>* Intranasal application<br>* Other names: NoAl;|
| Placebo Comparator: Group B<br>One puff of oxymetazoline immediately followed by one puff of placebo, morning & evening, for 8 days. | Drug: Oxymetazoline<br>* Intranasal application<br>* Other names: Afrin;Other: Placebo (lactose powder)<br>* Intranasal application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak nasal inspiratory flow (PNIF) area under the curve (AUC) change between the placebo and active NoAl treatment on day 1 |  | PNIF on Day 1, 8 and 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between the PNIF AUC D1-D8 differences between the two groups |  | PNIF on D1 and D8 | 
| Differences in nasal mucociliary clearance (Saccharine test) between both groups. |  | Performed on D1, D8 and D15 | 
| Visual analogue scale (VAS) for the separate rhinitis symptoms between the two groups |  | On D1, D8 and D15 | 
| Change of each symptom score for congestion over 8 days |  | From D1 to D8 | 
| Change of total rhinitis symptom score (TRSS) over 8 days |  | From D1 to D8 | 
| Difference in the applied rescue decongestant (total number of additional puffs of oxymetazoline or any other medications indicated for the treatment of allergic rhinitis) as needed between the two groups |  | For 15 days | 
| Number and severity of adverse events |  | 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allergic Rhinitis, Congestion, Mucoadhesive Treatment, Nasal Decongestant