Clinical trial NCT01018030: Dose Finding Study of Fluticasone Furoate Nasal Spray for Uncomplicated Acute Rhinosinusitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sinusitis, Acute
Keywords: uncomplicated acute rhinosinusitis
fluticasone furoate
sinusitis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-11-23
Enrollment: 741
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period (Weeks 1-2)
timeFrame: Baseline and entire treatment period (up to 2 weeks)
Secondary outcomes:
measure: First Time to Symptom Improvement
timeFrame: Entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in AM MSS
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in PM MSS
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in the Daily Nasal Congestion/Stuffiness Score
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in the AM Nasal Congestion/Stuffiness Score
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in the PM Nasal Congestion/Stuffiness Score
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in the Daily Sinus Headache/Pressure or Facial Pain/Pressure Score
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in the AM Sinus Headache/Pressure or Facial Pain/Pressure Score
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in the PM Sinus Headache/Pressure or Facial Pain/Pressure Score
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in the Daily Postnasal Drip Score
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in the AM Postnasal Drip Score
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Mean Change From Baseline Over the Entire Treatment Period in the PM Postnasal Drip Score
timeFrame: Baseline and entire treatment period (up to 2 weeks)
measure: Number of Participants Who Require the Use of an Antibiotic Due to the Development of Fulminant Bacterial Rhinosinusitis (FBRS)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Ruse
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Varna
country: Bulgaria
facility: GSK Investigational Site
city: Chilliwack
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Kelowna
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: GSK Investigational Site
state: Manitoba
city: Winnipeg
country: Canada
facility: GSK Investigational Site
state: Manitoba
city: Ajax
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Newmarket
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Oshawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Woodstock
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Granby
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: GSK Investigational Site
state: Saskatchewan
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Benesov
country: Czechia
facility: GSK Investigational Site
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
city: Pardubice
country: Czechia
facility: GSK Investigational Site
city: Praha 5
country: Czechia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Weinheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Nuernberg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Ketzin
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Duisburg
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Goch
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Delitzsch
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Schmoelln
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Almere
country: Netherlands
facility: GSK Investigational Site
city: Beek
country: Netherlands
facility: GSK Investigational Site
city: Etten-leur
country: Netherlands
facility: GSK Investigational Site
city: Losser
country: Netherlands
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Woerden
country: Netherlands
facility: GSK Investigational Site
city: Alesund
country: Norway
facility: GSK Investigational Site
city: Bekkestua
country: Norway
facility: GSK Investigational Site
city: Elverum
country: Norway
facility: GSK Investigational Site
city: Hamar
country: Norway
facility: GSK Investigational Site
city: Hønefoss
country: Norway
facility: GSK Investigational Site
city: Nesttun
country: Norway
facility: GSK Investigational Site
city: Stavanger
country: Norway
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Zawadzkie
country: Poland
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Benidorm/Alicante
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Oviedo
country: Spain
facility: GSK Investigational Site
city: Petrer/Alicante
country: Spain
facility: GSK Investigational Site
city: Talavera de la Reina (Toledo)
country: Spain
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Lidingö
country: Sweden
facility: GSK Investigational Site
city: Lund
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Odesa
country: Ukraine
facility: GSK Investigational Site
city: Symferopil
country: Ukraine
facility: GSK Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.