A Study Comparing Two Fluticasone Furoate Nasal Sprays in the Relief of the Signs and Symptoms of Seasonal Allergic Rhinitis

Study Overview
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Brief Summary
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This study compared the safety and efficacy of a generic fluticasone furoate (Lek Pharmaceuticals) nasal spray to the reference listed drug in the treatment of seasonal allergic rhinitis. Additionally both the test and the reference formulations were tested for superiority against a placebo nasal spray.

Detailed Description
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The study was designed as a double-blind, randomized, placebo-controlled, parallel group, multi-site to compare the clinical equivalence of the test formulation of fluticasone furoate, 27.5 mcg/actuation nasal spray (Lek Pharmaceuticals d.d.) with the reference formulation Veramyst® nasal spray (GlaxoSmithKline) in the relief of the signs and symptoms of seasonal allergic rhinitis. Participants who met the inclusion/exclusion criteria entered a 7-day placebo lead-in period. Following this placebo lead-in period, on Day 1 participants who continued to meet eligibility criteria were randomly assigned in a 2:2:1 ratio to one of three treatment groups (Test Product:Reference Product:Placebo) for 14 days of treatment. In all treatment groups, participants were instructed to administer the study drug once daily at approximately the same time each day. A single dose of 110 mcg was 4 actuations, each containing 27.5 mcg per actuation. Patients were instructed to administer the 4 actuations alternating between right and left nostril, such that 2 actuations were not administered back to back to the same nostril.

Official Title
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A Double-Blind, Randomized, Placebo Controlled, Parallel Group, Multi-Site Study to Compare the Clinical Equivalence of Fluticasone Furoate Nasal Spray (Lek Pharmaceuticals) With Veramyst® Nasal Spray (GlaxoSmithKline) in the Relief of the Signs and Symptoms of Seasonal Allergic Rhinitis

Conditions
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Rhinitis, Allergic, Seasonal

Intervention / Treatment
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* Drug: Fluticasone furoate 27.5 mcg/actuation nasal spray (Lek Pharmaceuticals)
* Drug: Fluticasone furoate (Veramyst®) 27.5 mcg/actuation nasal spray
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant, non-lactating female 12 years of age or older with a minimum of 2 years of previous history of seasonal allergic rhinitis to the pollen/allergen in season at the time the study is being conducted. Signed informed consent (assent) form. Documented positive allergic skin test to local pollen. An average score of at least 6 on the reflective Total Nasal Symptom Score (rTNSS) with a minimum score of at least 2 for nasal congestion and at least 4 on the reflective Total Ocular Symptom Score (rTOSS). Exclusion Criteria: History of asthma that required chronic therapy (with the exception of occasional acute or mild exercise induced asthma). Some other past and concomitant medical conditions, prohibited medications. Upper respiratory tract infection or any untreated infections. Patient has started immunotherapy/changed the dose. Any known allergy to any of the components of the study nasal spray.

Ages Eligible for Study
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Minimum Age: 12 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test<br>Fluticasone furoate 27.5 mcg/actuation nasal spray (Lek Pharmaceuticals) administered once daily at a dose of 110 mcg (4 actuations) for 14 days. | Drug: Fluticasone furoate 27.5 mcg/actuation nasal spray (Lek Pharmaceuticals)<br>* Nasal spray administered once daily at a dose of 110 mcg (4 actuations) for 14 days.<br>|
| Active Comparator: Reference<br>Fluticasone furoate (Veramyst®) 27.5 mcg/actuation nasal spray administered once daily at a dose of 110 mcg (4 actuations) for 14 days. | Drug: Fluticasone furoate (Veramyst®) 27.5 mcg/actuation nasal spray<br>* Nasal spray administered once daily at a dose of 110 mcg (4 actuations) for 14 days.<br>|
| Placebo Comparator: Placebo<br>Placebo nasal spray administered once daily for 14 days. | Drug: Placebo<br>* Placebo nasal spray administered once daily (4 actuations) for 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Equivalence: Per-Protocol Population) | Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTNSS patients were asked to look back or reflect on their severity of nasal symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline rTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTNSS - mean post-randomization rTNSS. A positive change from baseline in rTNSS is considered a favorable outcome. | Baseline, 14 days | 
| PRIMARY: Mean Change From Baseline in Reflective Total Nasal Symptom Score (rTNSS) (Superiority: Intent-to-Treat Population) | Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTNSS patients were asked to look back or reflect on their severity of nasal symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline rTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTNSS - mean post-randomization rTNSS. A positive change from baseline in rTNSS is considered a favorable outcome. | Baseline, 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Equivalence: Per-Protocol Population) | Participants were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTNSS participants were asked to evaluate how I feel now regarding their severity of nasal symptoms. The first rating on each day was taken prior to dosing. Participants were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean iTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline iTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTNSS - mean post-randomization iTNSS. A positive change from baseline in iTNSS is considered a favorable outcome. | Baseline, 14 days | 
| Mean Change From Baseline in Instantaneous Total Nasal Symptom Score (iTNSS) (Superiority: Intent-to-Treat Population) | Participants were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTNSS participants were asked to evaluate how I feel now regarding their severity of nasal symptoms. The first rating on each day was taken prior to dosing. Participants were asked to score 4 nasal symptoms (nasal congestion, runny nose, sneezing and itchy nose) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 4 individual symptom scores obtained over the randomized treatment period were summed to give the mean iTNSS, which ranged from 0 to 12 with a lower score indicating less severe symptoms. Mean baseline iTNSS was calculated by summing the means of the 4 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTNSS - mean post-randomization iTNSS. A positive change from baseline in iTNSS is considered a favorable outcome. | Baseline, 14 days | 
| Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Equivalence: Per-Protocol Population) | Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTOSS patients were asked to look back or reflect on their severity of ocular symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTOSS - mean post-randomization rTOSS. A positive change from baseline is considered a favorable outcome. | Baseline, 14 days | 
| Mean Change From Baseline in Reflective Total Ocular Symptom Score (rTOSS) (Superiority: Intent-to-Treat Population) | Patients were required to record a 12 hour reflective score twice a day approximately 12 hours apart. For the rTOSS patients were asked to look back or reflect on their severity of ocular symptoms over the previous 12 hours. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline rTOSS - mean post-randomization rTOSS. A positive change from baseline is considered a favorable outcome. | Baseline, 14 days | 
| Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Equivalence: Per-Protocol Population) | Patients were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTOSS patients were asked to evaluate how I feel now regarding their severity of ocular symptoms. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTOSS - mean post-randomization iTOSS. A positive change from baseline in iTOSS is considered a favorable outcome. | Baseline, 14 days | 
| Mean Change From Baseline in Instantaneous Total Ocular Symptom Score (iTOSS) (Superiority: Intent-to-Treat Population) | Patients were required to record an instantaneous score twice a day approximately 12 hours apart. For the iTOSS patients were asked to evaluate how I feel now regarding their severity of ocular symptoms. The first rating on each day was taken prior to dosing. Patients were asked to score 3 ocular symptoms (eye redness, itching/burning eyes, and tearing/watering eyes) on a 4 point scale ranging from 0 (no symptom) to 3 (severe symptom). The means of the 3 individual symptom scores obtained over the randomized treatment period were summed to give the mean rTOSS, which ranged from 0 to 9 with a lower score indicating less severe symptoms. Mean baseline rTOSS was calculated by summing the means of the 3 individual symptom scores obtained over the 72 hours before the randomized treatment period. Mean change from baseline was calculated as mean baseline iTOSS - mean post-randomization iTOSS. A positive change from baseline in iTOSS is considered a favorable outcome. | Baseline, 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rhinitis, Seasonal Allergic Rhinitis, Fluticasone furoate, Equivalence, Hay fever