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

Sinusitis, Acute Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01018030
• Other study ID #: 113203
• Status: Completed
• Phase: Phase 2
• First received: November 19, 2009
• Last updated: March 21, 2017
• Start date: January 2010
• Est. completion date: July 2010

Study information

• Verified date: March 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 741
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sinusitis
• Sinusitis, Acute

Intervention

Drug:
• FFNS 110 mcg QD
Active Nasal Spray (AM) and Placebo Nasal Spray (PM)
• FFNS 110 mcg BID
Active Nasal Spray (AM) and Active Nasal Spray (PM)
• Placebo Nasal Spray
Placebo Nasal Spray (AM) and Placebo Nasal Spray (PM)

Locations

Country	Name	City	State
Bulgaria	GSK Investigational Site	Ruse
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Varna
Canada	GSK Investigational Site	Ajax	Ontario
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Chilliwack	British Columbia
Canada	GSK Investigational Site	Granby	Quebec
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	Kelowna	British Columbia
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Newmarket	Ontario
Canada	GSK Investigational Site	Oshawa	Ontario
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Pointe-Claire	Quebec
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Quebec City	Quebec
Canada	GSK Investigational Site	Sarnia	Ontario
Canada	GSK Investigational Site	Saskatoon	Saskatchewan
Canada	GSK Investigational Site	Sudbury	Ontario
Canada	GSK Investigational Site	Surrey	British Columbia
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Winnipeg	Manitoba
Canada	GSK Investigational Site	Winnipeg	Manitoba
Canada	GSK Investigational Site	Woodstock	Ontario
Czech Republic	GSK Investigational Site	Benesov
Czech Republic	GSK Investigational Site	Brno
Czech Republic	GSK Investigational Site	Hradec Kralove
Czech Republic	GSK Investigational Site	Pardubice
Czech Republic	GSK Investigational Site	Praha 5
Estonia	GSK Investigational Site	Tallinn
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Delitzsch	Sachsen
Germany	GSK Investigational Site	Duisburg	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Goch	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Ketzin	Brandenburg
Germany	GSK Investigational Site	Nuernberg	Bayern
Germany	GSK Investigational Site	Schmoelln	Thueringen
Germany	GSK Investigational Site	Weinheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Wiesbaden	Hessen
Netherlands	GSK Investigational Site	Almere
Netherlands	GSK Investigational Site	Beek
Netherlands	GSK Investigational Site	Etten-leur
Netherlands	GSK Investigational Site	Losser
Netherlands	GSK Investigational Site	Nijmegen
Netherlands	GSK Investigational Site	Woerden
Norway	GSK Investigational Site	Alesund
Norway	GSK Investigational Site	Bekkestua
Norway	GSK Investigational Site	Elverum
Norway	GSK Investigational Site	Hamar
Norway	GSK Investigational Site	Hønefoss
Norway	GSK Investigational Site	Nesttun
Norway	GSK Investigational Site	Stavanger
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Tarnow
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Zawadzkie
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Saint-Petersburg
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Benidorm/Alicante
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Oviedo
Spain	GSK Investigational Site	Petrer/Alicante
Spain	GSK Investigational Site	Talavera de la Reina (Toledo)
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Göteborg
Sweden	GSK Investigational Site	Lidingö
Sweden	GSK Investigational Site	Lund
Sweden	GSK Investigational Site	Stockholm
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Kyiv
Ukraine	GSK Investigational Site	Odesa
Ukraine	GSK Investigational Site	Symferopil
Ukraine	GSK Investigational Site	Zaporizhzhya

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Bulgaria,  Canada,  Czech Republic,  Estonia,  Germany,  Netherlands,  Norway,  Poland,  Russian Federation,  Spain,  Sweden,  Ukraine, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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