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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01018030

Enrollment

741

Registered

2009-11-23

Start date

2010-01-06

Completion date

2010-07-16

Last updated

2017-05-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sinusitis, Acute

Keywords

uncomplicated acute rhinosinusitis, fluticasone furoate, sinusitis

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.

Interventions

DRUGFFNS 110 mcg QD

Active Nasal Spray (AM) and Placebo Nasal Spray (PM)

DRUGFFNS 110 mcg BID

Active Nasal Spray (AM) and Active Nasal Spray (PM)

DRUGPlacebo Nasal Spray

Placebo Nasal Spray (AM) and Placebo Nasal Spray (PM)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

12 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period (Weeks 1-2)	Baseline and entire treatment period (up to 2 weeks)	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

Measure	Time frame	Description
Mean Change From Baseline Over the Entire Treatment Period in AM MSS	Baseline and entire treatment period (up to 2 weeks)	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	Baseline and entire treatment period (up to 2 weeks)	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	Baseline and entire treatment period (up to 2 weeks)	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	Baseline and entire treatment period (up to 2 weeks)	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	Baseline and entire treatment period (up to 2 weeks)	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	Baseline and entire treatment period (up to 2 weeks)	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).
First Time to Symptom Improvement	Entire treatment period (up to 2 weeks)	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 the PM Sinus Headache/Pressure or Facial Pain/Pressure Score	Baseline and entire treatment period (up to 2 weeks)	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	Baseline and entire treatment period (up to 2 weeks)	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	Baseline and entire treatment period (up to 2 weeks)	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	Baseline and entire treatment period (up to 2 weeks)	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)	4 weeks	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.
Mean Change From Baseline Over the Entire Treatment Period in the AM Sinus Headache/Pressure or Facial Pain/Pressure Score	Baseline and entire treatment period (up to 2 weeks)	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).

Countries

Bulgaria, Canada, Czechia, Estonia, Germany, Netherlands, Norway, Poland, Russia, Spain, Sweden, Ukraine

Participant flow

Recruitment details

Participants were randomized to a double-blind, placebo-controlled, parallel-group, 2-week treatment study to evaluate the safety and efficacy of fluticasone furoate nasal spray 110 micrograms (either once or twice daily) for the treatment of uncomplicated acute rhinosinusitis in adults and adolescent participants 12 years of age and older.

Participants by arm

Arm	Count
Placebo Vehicle Placebo Nasal Spray administered twice daily (BD) for 14 days	245
FFNS 110 mcg QD Fluticasone Furoate Nasal Spray (FFNS) 110 micrograms (mcg) administered once daily (QD) in the morning and vehicle placebo nasal spray administered in the evening for 14 days	240
FFNS 110 mcg BD FFNS 110 mcg administered BD for 14 days	252
Total	737

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	10	5	5
Overall Study	Did Not Receive Study Drug	1	3	0
Overall Study	Lack of Efficacy	1	0	0
Overall Study	Lost to Follow-up	2	0	3
Overall Study	Physician Decision	1	0	1
Overall Study	Protocol Violation	2	1	0
Overall Study	Withdrawal by Subject	2	2	4

Baseline characteristics

Characteristic	Placebo	FFNS 110 mcg QD	FFNS 110 mcg BD	Total
Age, Continuous	39.1 Years STANDARD_DEVIATION 14.81	39.7 Years STANDARD_DEVIATION 15.64	39.0 Years STANDARD_DEVIATION 16.02	39.3 Years STANDARD_DEVIATION 15.48
Race/Ethnicity, Customized Black	3 participants	0 participants	3 participants	6 participants
Race/Ethnicity, Customized Other (Other than White and Black)	4 participants	6 participants	5 participants	15 participants
Race/Ethnicity, Customized White	238 participants	234 participants	244 participants	716 participants
Sex: Female, Male Female	143 Participants	148 Participants	169 Participants	460 Participants
Sex: Female, Male Male	102 Participants	92 Participants	83 Participants	277 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	41 / 245	41 / 240	46 / 252
serious Total, serious adverse events	0 / 245	0 / 240	1 / 252

Outcome results

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).

Time frame: Baseline and entire treatment period (up to 2 weeks)

Population: Intent-to-Treat (ITT) Population: all randomized participants who received at least one dose of double-blind study drug. Participants with missing diary data at baseline or post-baseline were not included in this analysis.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period (Weeks 1-2)	-2.97 units on a scale	Standard Error 0.12
FFNS 110 mcg QD	Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period (Weeks 1-2)	-3.36 units on a scale	Standard Error 0.13
FFNS 110 mcg BD	Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period (Weeks 1-2)	-3.33 units on a scale	Standard Error 0.13

p-value: 0.00895% CI: [-0.67, -0.1]ANCOVA

p-value: 0.01495% CI: [-0.64, -0.07]ANCOVA

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.

Time frame: Entire treatment period (up to 2 weeks)