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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01018030
First received: November 19, 2009
Last updated: June 20, 2013
Last verified: April 2011
  Purpose

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).


Condition Intervention Phase
Sinusitis, Acute
Drug: FFNS 110 mcg QD
Drug: FFNS 110 mcg BID
Drug: Placebo Nasal Spray
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period (Weeks 1-2) [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • First Time to Symptom Improvement [ Time Frame: Entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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.

  • Mean Change From Baseline Over the Entire Treatment Period in AM MSS [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in PM MSS [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in the Daily Nasal Congestion/Stuffiness Score [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in the AM Nasal Congestion/Stuffiness Score [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in the PM Nasal Congestion/Stuffiness Score [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in the Daily Sinus Headache/Pressure or Facial Pain/Pressure Score [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in the AM Sinus Headache/Pressure or Facial Pain/Pressure Score [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in the PM Sinus Headache/Pressure or Facial Pain/Pressure Score [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in the Daily Postnasal Drip Score [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in the AM Postnasal Drip Score [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Mean Change From Baseline Over the Entire Treatment Period in the PM Postnasal Drip Score [ Time Frame: Baseline and entire treatment period (up to 2 weeks) ] [ Designated as safety issue: No ]
    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).

  • Number of Participants Who Require the Use of an Antibiotic Due to the Development of Fulminant Bacterial Rhinosinusitis (FBRS) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 741
Study Start Date: January 2010
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Placebo Comparator: Placebo Nasal Spray Drug: Placebo Nasal Spray
Placebo Nasal Spray (AM) and Placebo Nasal Spray (PM)

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

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01018030

Locations
Czech Republic
GSK Investigational Site
Benesov, Czech Republic, 256 30
GSK Investigational Site
Brno, Czech Republic, 662 63
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 05
GSK Investigational Site
Pardubice, Czech Republic, 532 03
GSK Investigational Site
Praha 5, Czech Republic, 150 06
Netherlands
GSK Investigational Site
Almere, Netherlands, 1311 RL
GSK Investigational Site
Beek, Netherlands, 6191 JW
Norway
GSK Investigational Site
Alesund, Norway
GSK Investigational Site
Bekkestua, Norway, N-1357
GSK Investigational Site
Elverum, Norway, 2408
GSK Investigational Site
Hamar, Norway, 2317
GSK Investigational Site
Nesttun, Norway, N-5227
GSK Investigational Site
Stavanger, Norway, 4011
Sweden
GSK Investigational Site
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
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01018030     History of Changes
Other Study ID Numbers: 113203
Study First Received: November 19, 2009
Results First Received: March 17, 2011
Last Updated: June 20, 2013
Health Authority: Estonia: State Agency of Medicines
Spain: Agencia Española del Medicamento y Productos Sanitarios
Germany: Land Authority for Health and Social Issues
Poland: URZAD REJESTRACJI PRODUKTOW LECZNICZYCH, WYROBOW MEDYCZNYCH I PRODUKTOW BIOBOJCZYCH
Ukraine: The Central Ethics Committee of Ministry of Health of Ukraine
Russia: Federal Service of Surveillance in Healthcare and Social development of Russian federation
Ukraine: State Pharmacological Center of Ministry of Health of Ukraine
Canada: Health Canada
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Norway: National Health Services
Sweden: Medical Products Agency
Czech: State Institute for Drug Control
Bulgaria: Bulgarian Drug Agency (BDA)
Europe: European Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by GlaxoSmithKline:
uncomplicated acute rhinosinusitis
fluticasone furoate
sinusitis

Additional relevant MeSH terms:
Sinusitis
Paranasal Sinus Diseases
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Fluticasone
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 24, 2014