Dose Finding Study of Fluticasone Furoate Nasal Spray for Uncomplicated Acute Rhinosinusitis

A Randomized, Double-blind, Placebo Controlled, Parallel Group, Multi-centre, 2-week Treatment Study to Evaluate the Safety and Efficacy of Fluticasone Furoate Nasal Spray 110 mcg in the Treatment in the Treatment of Uncomplicated Acute Rhinosinusitis in Adults and Adolescents >= 12 Years of Age

The purpose of this study is to assess the safety and efficacy of fluticasone furoate nasal spray (FFNS), without the use of an antibiotic, in the treatment of adult and adolescent subjects who are 12 years of age and older with uncomplicated acute rhinosinusitis (ARS).

Study Overview

• Status: Completed
• Conditions: Sinusitis, Acute
• Intervention / Treatment: Drug: FFNS 110 mcg QD; Drug: FFNS 110 mcg BID; Drug: Placebo Nasal Spray

Detailed Description

- Rationale - Acute rhinosinusitis (ARS) is a condition caused by inflammation of the nose and the paranasal sinuses that generally lasts up to 4 weeks. Despite ARS being a self-limiting condition, untreated or inadequately treated sinus infection can lead to the development of complications. Uncomplicated ARS is a subset of ARS and is distinguished from the common cold by the persistence or the worsening of sinus inflammation after the usual period for recovery of viral infection of the nasal cavity (i.e., 10 days). Clinically the difference is based on the following criteria: symptoms are present at least 10 days but less than 4 weeks beyond the onset of upper respiratory symptoms OR symptoms worsen after 5 days from their onset.

In the primary care settings, ARS is often treated empirically with antibiotics although they are shown to provide limited benefit in the uncomplicated ARS population. Alternatively, the use of an intranasal corticosteroid (INS) to control symptoms of uncomplicated ARS is plausible based on clinically proven ability to reduce inflammation and mucosal swelling.

This study is a phase II study.

• Objective - The objective of this study is to evaluate the safety and efficacy of two doses of FFNS (110 mcg once daily and 110 mcg twice daily) compared to placebo as monotherapy in the treatment of adult and adolescent subjects 12 years of age and older with uncomplicated ARS.
• Study Design - This is a randomized, double-blind, placebo controlled, parallel group, multi-centre, 2-week treatment study. The study includes a 2-week post-treatment follow-up period.

Approximately 720 subjects will be randomized to one of three treatment groups for a period of 14 days: FFNS 110 mcg QD, FFNS 110 mcg BID, and placebo nasal spray.

• Study Type: Interventional
• Enrollment (Actual): 741
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Ruse, Bulgaria, 7000
    • GSK Investigational Site
  • Sofia, Bulgaria, 1606
    • GSK Investigational Site
  • Sofia, Bulgaria, 1527
    • GSK Investigational Site
  • Sofia, Bulgaria, 1000
    • GSK Investigational Site
  • Varna, Bulgaria, 9010
    • GSK Investigational Site
• Canada
  • Quebec, Canada, G1W 4R4
    • GSK Investigational Site
  • British Columbia
    • Chilliwack, British Columbia, Canada, V2P 4M9
      • GSK Investigational Site
    • Kelowna, British Columbia, Canada, V1Y 9L8
      • GSK Investigational Site
    • Surrey, British Columbia, Canada, V4H 2H9
      • GSK Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2V 4W3
      • GSK Investigational Site
    • Winnipeg, Manitoba, Canada, R3C 3J5
      • GSK Investigational Site
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • GSK Investigational Site
    • Brampton, Ontario, Canada, L6T 3T1
      • GSK Investigational Site
    • Hamilton, Ontario, Canada, L8N 3Z5
      • GSK Investigational Site
    • London, Ontario, Canada, N5W 6A2
      • GSK Investigational Site
    • Mississauga, Ontario, Canada, L5A 3V4
      • GSK Investigational Site
    • Newmarket, Ontario, Canada, L3Y 5G8
      • GSK Investigational Site
    • Oshawa, Ontario, Canada, L1H 7K4
      • GSK Investigational Site
    • Ottawa, Ontario, Canada, K1Y 4G2
      • GSK Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • GSK Investigational Site
    • Sudbury, Ontario, Canada, P3E 1H5
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M9W 4L6
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M3H 5S4
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M4P 1P2
      • GSK Investigational Site
    • Woodstock, Ontario, Canada, N4S 5P5
      • GSK Investigational Site
  • Quebec
    • Granby, Quebec, Canada, J2G 8Z9
      • GSK Investigational Site
    • Pointe-Claire, Quebec, Canada, H9R 4S3
      • GSK Investigational Site
    • Quebec City, Quebec, Canada, G1V 4M6
      • GSK Investigational Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 3H3
      • GSK Investigational Site
• Czechia
  • Benesov, Czechia, 256 30
    • GSK Investigational Site
  • Brno, Czechia, 662 63
    • GSK Investigational Site
  • Hradec Kralove, Czechia, 500 05
    • GSK Investigational Site
  • Pardubice, Czechia, 532 03
    • GSK Investigational Site
  • Praha 5, Czechia, 150 06
    • GSK Investigational Site
• Estonia
  • Tallinn, Estonia, 13619
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 12157
    • GSK Investigational Site
  • Berlin, Germany, 13057
    • GSK Investigational Site
  • Hamburg, Germany, 22143
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Weinheim, Baden-Wuerttemberg, Germany, 69469
      • GSK Investigational Site
  • Bayern
    • Nuernberg, Bayern, Germany, 90443
      • GSK Investigational Site
  • Brandenburg
    • Ketzin, Brandenburg, Germany, 14669
      • GSK Investigational Site
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • GSK Investigational Site
    • Wiesbaden, Hessen, Germany, 65183
      • GSK Investigational Site
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Duisburg, Nordrhein-Westfalen, Germany, 47051
      • GSK Investigational Site
    • Essen, Nordrhein-Westfalen, Germany, 45359
      • GSK Investigational Site
    • Goch, Nordrhein-Westfalen, Germany, 47574
      • GSK Investigational Site
  • Sachsen
    • Delitzsch, Sachsen, Germany, 04509
      • GSK Investigational Site
  • Thueringen
    • Schmoelln, Thueringen, Germany, 04626
      • GSK Investigational Site
• Netherlands
  • Almere, Netherlands, 1311 RL
    • GSK Investigational Site
  • Beek, Netherlands, 6191 JW
    • GSK Investigational Site
  • Etten-leur, Netherlands, 4872 LA
    • GSK Investigational Site
  • Losser, Netherlands, 7581 BV
    • GSK Investigational Site
  • Nijmegen, Netherlands, 6525 EC
    • GSK Investigational Site
  • Woerden, Netherlands, 3443 GG
    • GSK Investigational Site
• Norway
  • Alesund, Norway
    • GSK Investigational Site
  • Bekkestua, Norway, 1319
    • GSK Investigational Site
  • Elverum, Norway, 2408
    • GSK Investigational Site
  • Hamar, Norway, 2317
    • GSK Investigational Site
  • Hønefoss, Norway, N-3515
    • GSK Investigational Site
  • Nesttun, Norway, N-5227
    • GSK Investigational Site
  • Stavanger, Norway, 4011
    • GSK Investigational Site
• Poland
  • Lublin, Poland, 20-637
    • GSK Investigational Site
  • Tarnow, Poland, 33-100
    • GSK Investigational Site
  • Wroclaw, Poland, 50-556
    • GSK Investigational Site
  • Wroclaw, Poland, 53-146
    • GSK Investigational Site
  • Zawadzkie, Poland, 47-120
    • GSK Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 123095
    • GSK Investigational Site
  • Moscow, Russian Federation, 119881
    • GSK Investigational Site
  • Moscow, Russian Federation, 129010
    • GSK Investigational Site
  • Saint-Petersburg, Russian Federation, 190013
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08036
    • GSK Investigational Site
  • Benidorm/Alicante, Spain, 03503
    • GSK Investigational Site
  • Madrid, Spain, 28040
    • GSK Investigational Site
  • Oviedo, Spain
    • GSK Investigational Site
  • Petrer/Alicante, Spain, 03610
    • GSK Investigational Site
  • Talavera de la Reina (Toledo), Spain, 45600
    • GSK Investigational Site
• Sweden
  • Göteborg, Sweden, SE-402 76
    • GSK Investigational Site
  • Göteborg, Sweden, SE-411 21
    • GSK Investigational Site
  • Lidingö, Sweden, SE-181 58
    • GSK Investigational Site
  • Lund, Sweden, SE-221 85
    • GSK Investigational Site
  • Stockholm, Sweden, SE-141 86
    • GSK Investigational Site
• Ukraine
  • Kyiv, Ukraine, 01103
    • GSK Investigational Site
  • Kyiv, Ukraine, 03057
    • GSK Investigational Site
  • Odesa, Ukraine, 65009
    • GSK Investigational Site
  • Symferopil, Ukraine, 95017
    • GSK Investigational Site
  • Zaporizhzhya, Ukraine, 69000
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent
2. Outpatient
3. Age (>= 18 years at Visit 1 for Russia, Ukraine, and Germany; >= 12 years at Visit 2 for all other countries)
4. Diagnosis of uncomplicated acute rhinosinusitis
5. Ability and willingness to comply with study procedures and restrictions.
6. Male or eligible female - Female subjects should not be enrolled if they plan to become pregnant during the time of study participation; To be eligible for entry into the study, females of childbearing potential must commit to the consistent and correct use of an acceptable method of birth control.
7. Literate

Exclusion Criteria:

1. Based on the investigator's clinical judgement, subject has fulminant bacterial rhinosinusitis during the screening period including Visits 1 and 2.
2. A history of acute rhinosinusitis within 12 weeks prior to the current episode as determined by the investigator
3. Current or a history of other sinonasal conditions (e.g., chronic or recurrent rhinosinusitis, non-allergic rhinitis) within 3 years prior to Visit 1 as determined by the investigator
4. Symptomatic perennial or seasonal allergic rhinitis prior to ARS episode, or allergy to seasonal allergens likely to be present during the study period (as determined by documented skin prick test or in vitro blood test).
5. Significant concomitant medical conditions
6. Subjects with planned elective surgery, vacation or other event during the study period which could prevent the subject from participating in the study according to protocol specifications
7. Use of antibiotics within 30 days prior to Visit 1 for sinopulmonary infections.
8. Use of antiviral medications such as zanamivir and oseltamivir within 30 days prior to Visit 1
9. Use of analgesics or antipyretics within 1 day prior to Visit 1
10. Known hypersensitivity or allergy to corticosteroids or any excipients in the product
11. Use of corticosteroids, defined as:
12. Use of any other medications that may affect nasal symptoms
13. Use of immunosuppressive medications eight weeks prior to screening and during the study
14. Immunotherapy
15. Use of any medications that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazole
16. Clinical trial/experimental medication experience
17. Positive pregnancy test or inconclusive pregnancy test or female who is breastfeeding
18. Affiliation with investigational site
19. Current tobacco use
20. Chicken pox or measles

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Nasal Spray	Drug: Placebo Nasal Spray; Placebo Nasal Spray (AM) and Placebo Nasal Spray (PM)
Experimental: FFNS 110 mcg QD	Drug: FFNS 110 mcg QD; Active Nasal Spray (AM) and Placebo Nasal Spray (PM)
Experimental: FFNS 110 mcg BID	Drug: FFNS 110 mcg BID; Active Nasal Spray (AM) and Active Nasal Spray (PM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period (Weeks 1-2)	The MSS was calculated as the sum of 3 individual symptom scores for nasal congestion/stuffiness, sinus headache/pressure or facial pain/pressure, and postnasal drip. Daily MSS was calculated as the average of the morning (AM) and evening (PM) MSS. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The total score ranged from 0 to 9. Change from baseline was calculated as the daily MSS averaged over the entire treatment period minus daily MSS over the baseline period (defined as the average daily MSS over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First Time to Symptom Improvement	Symptom improvement was defined as symptom scores less than or equal to 1 (i.e., mild or no symptoms) for all three major symptoms (nasal congestion/stuffiness, sinus headache/pressure or facial pain/pressure, and postnasal drip) on 2 consecutive 12-hour assessments. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe.	Entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in AM MSS	Mean change from baseline in MSS for nasal congestion/stuffiness, sinus headache/pressure or facial pain/pressure, and postnasal drip as measured in the morning (AM) was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The total score ranged from 0 to 9. Change from baseline in AM MSS was calculated as the AM MSS averaged over the entire treatment period minus the AM MSS over the baseline period (defined as the average AM MSS over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in PM MSS	Mean change from baseline in MSS for nasal congestion/stuffiness, sinus headache/pressure or facial pain/pressure, and postnasal drip as measured in the evening (PM) was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The total score ranged from 0 to 9. Change from baseline in PM MSS was calculated as the PM MSS averaged over the entire treatment period minus the PM MSS over the baseline period (defined as the average PM MSS over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in the Daily Nasal Congestion/Stuffiness Score	Mean change from baseline was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The score ranged from 0 to 3. Change from baseline in the daily nasal congestion/stuffiness score was calculated as the daily score averaged over the entire treatment period minus the daily score over the baseline period (defined as the average daily score over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in the AM Nasal Congestion/Stuffiness Score	Mean change from baseline was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The score ranged from 0 to 3. Change from baseline in the AM nasal congestion/stuffiness score was calculated as the AM score averaged over the entire treatment period minus the AM score over the baseline period (defined as the average AM score over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in the PM Nasal Congestion/Stuffiness Score	Mean change from baseline was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The score ranged from 0 to 3. Change from baseline in the PM nasal congestion/stuffiness score was calculated as the PM score averaged over the entire treatment period minus the PM score over the baseline period (defined as the average PM score over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in the Daily Sinus Headache/Pressure or Facial Pain/Pressure Score	Mean change from baseline was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The score ranged from 0 to 3. Change from baseline in the daily sinus headache/pressure or facial pain/pressure score was calculated as the daily score averaged over the entire treatment period minus the daily score over the baseline period (defined as the average daily score over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in the AM Sinus Headache/Pressure or Facial Pain/Pressure Score	Mean change from baseline was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The score ranged from 0 to 3. Change from baseline in the AM sinus headache/pressure or facial pain/pressure score was calculated as the AM score averaged over the entire treatment period minus the AM score over the baseline period (defined as the average AM score over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in the PM Sinus Headache/Pressure or Facial Pain/Pressure Score	Mean change from baseline was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The score ranged from 0 to 3. Change from baseline in the PM sinus headache/pressure or facial pain/pressure score was calculated as the PM score averaged over the entire treatment period minus the PM score over the baseline period (defined as the average PM score over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in the Daily Postnasal Drip Score	Mean change from baseline was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The score ranged from 0 to 3. Change from baseline in the daily postnasal drip score was calculated as the daily postnasal drip score averaged over the entire treatment period minus the daily postnasal drip score over the baseline period (defined as the average daily postnasal drip score over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in the AM Postnasal Drip Score	Mean change from baseline was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The score ranged from 0 to 3. Change from baseline in the AM postnasal drip score was calculated as the AM postnasal drip score averaged over the entire treatment period minus the AM postnasal drip score over the baseline period (defined as the average AM postnasal drip score over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Mean Change From Baseline Over the Entire Treatment Period in the PM Postnasal Drip Score	Mean change from baseline was calculated as the Week 1-2 value minus the baseline value. Each individual symptom was scored on a scale of 0 to 3: 0=none; 1=mild; 2=moderate; 3=severe. The score ranged from 0 to 3. Change from baseline in the PM postnasal drip score was calculated as the PM postnasal drip score averaged over the entire treatment period minus the PM postnasal drip score over the baseline period (defined as the average PM postnasal drip score over the last 3 days prior to randomization).	Baseline and entire treatment period (up to 2 weeks)
Number of Participants Who Require the Use of an Antibiotic Due to the Development of Fulminant Bacterial Rhinosinusitis (FBRS)	Participants who required the use of an antibiotic due to the development of FBRS during the 2-week treatment period and the 2-week follow-up period were included in the analysis.	4 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Keith PK, Dymek A, Pfaar O, Fokkens W, Yun Kirby S, Wu W, Garris C, Topors N, Lee LA. Fluticasone furoate nasal spray reduces symptoms of uncomplicated acute rhinosinusitis: a randomised placebo-controlled study. Prim Care Respir J. 2012 Sep;21(3):267-75. doi: 10.4104/pcrj.2012.00039.

Study record dates

Study Major Dates

• Study Start: January 6, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 16, 2010

Study Registration Dates

• First Submitted: November 19, 2009
• First Submitted That Met QC Criteria: November 19, 2009
• First Posted (Estimate): November 23, 2009

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: April 20, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: sinusitis; fluticasone furoate; uncomplicated acute rhinosinusitis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Nose Diseases; Sinusitis
• Other Study ID Numbers: 113203