Fluticasone Furoate Nasal Spray Versus Oral Fexofenadine

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00435461
• Collaborator: (none)
• Enrollment: 1,000
• Locations: 6
• Duration (Months): 2.3
• Patients Per Site: 166.7
• Patients Per Site Per Month: 72.5

Study Details

Study Description

Brief Summary

The primary objective of this study is to compare the nighttime symptom relief of fluticasone furoate nasal spray and oral fexofenadine

Condition or Disease	Intervention/Treatment	Phase
Rhinitis, Allergic, Seasonal	Drug: Fluticasone furoate and fexofenadine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 1000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Primary Purpose: Treatment
• Official Title: A Comparison of Fluticasone Furoate Nasal Spray Versus Oral Fexofenadine in the Treatment of Seasonal Allergic Rhinitis
• Study Start Date: Dec 20, 2006
• Actual Primary Completion Date: Feb 1, 2007
• Actual Study Completion Date: Feb 28, 2007

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Symptoms Score (NSS) [Baseline (Day 1) and up to 2 Weeks]

   The NSS is a three-item questionnaire which assesses three aspects of allergic rhinitis symptoms at night which were rated using three 4-point scales, the sum of which comprises NSS. The total score ranged from 0 (best) to 9 (worst). The symptoms were: PM nasal congestion upon awakening (PMNCA) (0- None, 1- Mild, 2- Moderate, 3- Severe), difficulty in going to sleep due to nasal symptoms (DSNS) (0- Not at all, 1- Little, 2- Moderately, 3- Very), and nighttime awakenings due to nasal symptoms (NANS) (0- Not at all, 1- Once, 2- More than once, 3- I felt like I was awake all night). Each participant's Baseline NSS was defined as the average of the NSS calculated for the day of randomization and the three highest NSS scores calculated during the six days immediately prior to the day of randomization. Each participant's average change from Baseline NSS for Weeks 1-2 was the participant's average NSS over the treatment period minus the participant's Baseline NSS.

Secondary Outcome Measures

1. Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Nasal Symptom Scores (N-rTNSS) and Component Nasal Symptoms Score [Baseline (Day 1) and up to 2 Weeks]

   The nighttime reflective assessments were recorded each morning and assessed 4 nasal symptoms (rhinorrhea, nasal congestion, nasal itching, sneezing) at evening and night using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). Scores of each of the 4 symptoms were summed for each participant to create a N-rTNSS for each day. The total score ranged from 0 (best) to 12 (worst). Each participant's Baseline total score was average of nighttime total symptom score on day of randomization and 3 highest scores calculated for 6 days immediately prior to day of randomization. Each participant's average change from Baseline nighttime total symptom score for Weeks 1-2 was the participant's average Nighttime total symptom score over the treatment period minus the participant's Baseline score.

2. Mean Change From Baseline Over the Two-week Treatment Period in D-rTNSS [Baseline (Day 1) and up to 2 Weeks]

   The Daytime reflective assessments were recorded each evening and assessed 4 nasal symptoms (rhinorrhea, nasal congestion, nasal itching, and sneezing) at evening and night using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). The scores of each of the four Daytime symptoms were summed for each participant to create a D-rTNSS for each day. The total score ranged from 0 (best) to 12 (worst). Each participant's Baseline total symptom score was the average of the four highest total symptom score calculated for the seven days immediately prior to the day of randomization. Each participant's average change from Baseline Daytime total symptom score for Weeks 1-2 was the participant's average Daytime total symptom score over the treatment period minus the participants Baseline score.

3. Mean Change From Baseline Over the Two-week Treatment Period in 24-hour Reflective Total Nasal Symptom Scores (24-hour rTNSS) and Component Nasal Score [Baseline (Day 1) and up to 2 Weeks]

   Daily 24-hour rTNSS was calculated as the average of the corresponding N-rTNSS and D-rTNSS using a 4-point scale where, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). The total score ranged from 0 (best) to 12 (worst). The 24-hour total symptom score for a Day is the average of the daytime total symptom score for that Day and the nighttime score for (D+1). If either component of a given date's 24-hour total symptom score was missing, then the 24-hour total symptom score itself were to be set to missing. Each participant's average change from Baseline 24-hour total symptom score for Weeks 1-2 was the participants average 24-hour total symptom score over the treatment period minus the participant's Baseline score.

4. Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Ocular Symptom Scores (N-rTOSS) [Baseline (Day 1) and up to 2 Weeks]

   The nighttime reflective assessments were recorded each morning and assessed 3 ocular symptoms (tearing/watering, itching/burning, and redness) at evening and night using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). Scores of each of 3 Nighttime symptoms were summed for each participant to create a N-rTOSS for each day. The total score ranged from 0 (best) to 9 (worst). Each participants Baseline total score was average of nighttime total symptom score on day of randomization and the 3 highest scores calculated for 6 days immediately prior to the day of randomization. Each participant's average change from Baseline nighttime total symptom score for Weeks 1-2 was the participant's average Nighttime total symptom score over treatment period minus the participant's Baseline score.

5. Mean Change From Baseline Over the Two-week Treatment Period in Daytime Reflective Total Ocular Symptom Scores (D-rTOSS) [Baseline (Day 1) and up to 2 Weeks]

   The Daytime reflective assessments were recorded each evening and assessed the 3 nasal symptoms (tearing/watering, itching/burning, and redness) at evening and night using a 4-point scale where, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). The scores of each of the three Daytime symptoms were summed for each participant to create a D-rTOSS for each day. The total score ranged from 0 (best) to 9 (worst). Each participants Baseline total symptom score was the average of the four highest total symptom score calculated for the seven days immediately prior to the day of randomization. Each participant's average change from Baseline Daytime total symptom score for Weeks 1-2 was the participant's average Daytime total symptom score over the treatment period minus the participant's Baseline score.

6. Mean Change From Baseline Over the Two-week Treatment Period in 24-hour Reflective Total Ocular Symptom Scores (24-hour rTOSS) [Baseline (Day 1) and up to 2 Weeks]

   Daily 24-hour rTOSS was calculated as the average of the corresponding N-rTOSS and D-rTOSS using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). The total score ranged from 0 (best) to 9 (worst). The 24-hour total symptom score for a Day is the average of the daytime total symptom score for that Day and the nighttime score for (D+1). If either component of a given date's 24-hour total symptom score was missing, then the 24-hour total symptom score itself was to be set to missing. Each participant's average change from Baseline 24-hour total symptom score for Weeks 1-2 was the participant's average 24-hour total symptom score over the treatment period minus the participant's Baseline score. Baseline is the 4 highest scores calculated for the 7 days prior to Day 1.

7. Mean Change From Baseline Over the Two-week Treatment Period in Pre-dose Instantaneous Total Nasal Symptom Score (Pre-dose iTNSS) and Pre-dose Instantaneous Total Ocular Symptom Scores (Pre-dose iTOSS) [Baseline (Day 1) and up to 2 Weeks]

   Participants were instructed to score and document their symptoms in an instantaneous manner on a diary card. The instantaneous rating was performed once daily just prior to administering their morning dose. The scores of each of the instantaneous nasal symptoms (nasal congestion, itching, rhinorrhea, and sneezing) and ocular symptoms (tearing/watering, itching/burning, and redness) were summed for each participant to create a iTNSS and iTOSS, respectively using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). Total score ranged from 0 (best) to 12 (worst) for iTNSS and 0 (best) to 9 (worst) for iTOSS. Each participant's average change from Baseline iTNSS and iTOSS was participant's average iTNSS and iTOSS total score over the treatment period minus the participant's Baseline score.

8. Mean Change From Baseline Over the Two-week Treatment Period in Peak NasalIinspiratory Flow (PNIF) [Baseline (Day 1) and up to 2 Weeks]

   PNIF was measured by participants using an In-Check Nasal portable hand-held inspiratory flow meter and face mask. Participants recorded PNIF twice daily (in the morning prior to taking their study medication and in the evening). Three measurements were taken on each occasion and the highest measurement recorded on the electronic diary. Each participant's average change from Baseline PNIF was the participant's average PNIF over the treatment period minus the participant's baseline PNIF.

9. Mean Change From Baseline for Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) [Baseline (Day 1) and Day 15]

   The NRQLQ is a paper instrument administered on the day of randomization and at Visit 4/Early Withdrawal to assess nocturnal rhinitis-related quality of life. The NRQLQ is a 16-item, self-administered, disease-specific (allergic rhinitis), and quality of life instrument that measures the functional problems most troublesome to patients with nocturnal allergy symptoms over a one-week interval. Each question is scored from 0 to 6 with higher scores indicating more nocturnal impairment. Items are grouped into four domains: Sleep problems, Sleep time problems, Symptoms on waking in the morning and Practical problems. An overall score was calculated from the mean score of all items. Each participant's average change from Baseline NRQLQ score was the participant's average NRQLQ score over the treatment period minus the participant's baseline score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Informed consent.

• Outpatient.

• Females of child-bearing potential must use appropriate contraception.

• Diagnosis of seasonal allergic rhinitis to mountain cedar.

• Adequate exposure to allergen.

• Able to comply with study procedures.

• Literate.

Exclusion criteria:

• Significant concomitant medical condition.

• Use of corticosteroids, allergy medications, or other medication that affect allergic rhinitis

• Positive pregnancy test.

• Allergy to any component of the investigational product.

• Tobacco use

• Contact lens use

• Has chickenpox or measles or recent exposure

• Other clinical trial drug exposure in last 30 days

• Affiliation with clinic site

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Austin	Texas	United States	78731
2	GSK Investigational Site	Austin	Texas	United States	78750
3	GSK Investigational Site	Kerrville	Texas	United States	78028
4	GSK Investigational Site	New Braunfels	Texas	United States	78130
5	GSK Investigational Site	San Antonio	Texas	United States	78205
6	GSK Investigational Site	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Andrews C, Martin B, Jacobs R, Toler T, Prillaman B, Philpot E. Efficacy of fluticasone furoate nasal spray versus oral fexofenadine on nighttime sleep disturbance caused by seasonal allergic rhinitis (SAR) nasal symptoms. Ann Allergy Asthma Immunol 2008; 100(1) (Supplement 1):A6 (abstract)
• Andrews CP, Martin BG, Jacobs RL, Diaz J, Toler WT, Prillaman BA, Dalal AA, Philpot EE. Once-daily fluticasone furoate nasal spray showed greater improvement in nocturnal quality of life in subjects with seasonal allergic rhinitis compared with oral fexofenadine. J Allergy Clin Immunol 2008;121(2) (Supplement 1): S53 (abstract)
• Andrews CP, Martin BG, Jacobs RL, Mohar DE, Diaz JD, Amar NJ, Kaiser HB, Vandewalker ML, Bernstein J, Toler WT, Prillaman BA, Dalal AA, Lee LA, Philpot EE. Fluticasone furoate nasal spray is more effective than fexofenadine for nighttime symptoms of seasonal allergy. Allergy Asthma Proc. 2009 Mar-Apr;30(2):128-38. doi: 10.2500/aap.2009.30.3204.
• Martin BG, Andrews CP, Jacobs R, Mohar D, Toler WT, Prillaman BA, Philpot EE. Once-daily fluticasone furoate nasal spray showed greater improvements in relieving nighttime nasal symptoms and increasing peak nasal inspiratory flow versus oral fexofenadine in subjects with seasonal allergic rhinitis (SAR) J Allergy Clin Immunol 2008;121(2) (Supplement 1): S54-S55 (abstract)

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00435461
• Other Study ID Numbers: FFU109045
• First Posted: Feb 15, 2007
• Last Update Posted: Mar 7, 2018
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: once daily; mountain cedar; fexofenadine; allergic rhinitis; fluticasone furoate
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Fluticasone; Xhance; Fexofenadine

Study Results

Participant Flow

Recruitment Details	The study included 5-21 days of screening period followed by two weeks of treatment period and a Follow-up. Participants had to meet five symptom assessment criteria before randomization. Two of these were based on average Nasal Symptom Score assessment and three criteria's were based on the Daytime reflective Nasal Symptom Score (D-rTNSS).
Pre-assignment Detail	Total of 1360 participants were planned for enrollment so as to have 951 evaluable participants. A total of 1338 participants were screened and 936 were randomized.

Arm/Group Title	Placebo	FFNS 110 Microgram (mcg)	Fex 180 Milligram (mg)
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received fluticasone furoate nasal spray (FFNS) 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated fexofenadine [Fex] 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Period Title: Overall Study
STARTED	313	312	311
COMPLETED	290	298	287
NOT COMPLETED	23	14	24

Baseline Characteristics

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg	Total
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.	Total of all reporting groups
Overall Participants	313	312	311	936
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	37.8 (14.39)	37.8 (13.95)	39.6 (14.63)	38.4 (14.34)
Sex: Female, Male (Count of Participants)
Female	194 62%	209 67%	199 64%	602 64.3%
Male	119 38%	103 33%	112 36%	334 35.7%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	22 7%	26 8.3%	9 2.9%	57 6.1%
American Indian or Alaska Native	7 2.2%	5 1.6%	6 1.9%	18 1.9%
Asian - Central/South Asian Heritage	3 1%	1 0.3%	1 0.3%	5 0.5%
Asian - East Asian Heritage	1 0.3%	2 0.6%	0 0%	3 0.3%
Asian - Japanese Heritage	0 0%	1 0.3%	0 0%	1 0.1%
Asian - South East Asian Heritage	2 0.6%	1 0.3%	2 0.6%	5 0.5%
Native Hawaiian or other Pacific Islander	2 0.6%	1 0.3%	2 0.6%	5 0.5%
White/Caucasian/European Heritage	270 86.3%	268 85.9%	286 92%	824 88%
Mixed Race	6 1.9%	7 2.2%	5 1.6%	18 1.9%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Symptoms Score (NSS)
Description	The NSS is a three-item questionnaire which assesses three aspects of allergic rhinitis symptoms at night which were rated using three 4-point scales, the sum of which comprises NSS. The total score ranged from 0 (best) to 9 (worst). The symptoms were: PM nasal congestion upon awakening (PMNCA) (0- None, 1- Mild, 2- Moderate, 3- Severe), difficulty in going to sleep due to nasal symptoms (DSNS) (0- Not at all, 1- Little, 2- Moderately, 3- Very), and nighttime awakenings due to nasal symptoms (NANS) (0- Not at all, 1- Once, 2- More than once, 3- I felt like I was awake all night). Each participant's Baseline NSS was defined as the average of the NSS calculated for the day of randomization and the three highest NSS scores calculated during the six days immediately prior to the day of randomization. Each participant's average change from Baseline NSS for Weeks 1-2 was the participant's average NSS over the treatment period minus the participant's Baseline NSS.
Time Frame	Baseline (Day 1) and up to 2 Weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all participants randomized to double-blind treatment. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	312	312	309
NSS, Week 1-2	-1.9 (0.1)	-2.9 (0.1)	-2.0 (0.09)
PMNCA, Week 1-2	-0.6 (0.03)	-0.9 (0.03)	-0.6 (0.03)
NANS, Week 1-2	-0.7 (0.04)	-1.0 (0.04)	-0.7 (0.03)
DSNS, Week 1-2	-0.7 (0.04)	-1.1 (0.04)	-0.8 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.816
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

2. Secondary Outcome

Title	Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Nasal Symptom Scores (N-rTNSS) and Component Nasal Symptoms Score
Description	The nighttime reflective assessments were recorded each morning and assessed 4 nasal symptoms (rhinorrhea, nasal congestion, nasal itching, sneezing) at evening and night using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). Scores of each of the 4 symptoms were summed for each participant to create a N-rTNSS for each day. The total score ranged from 0 (best) to 12 (worst). Each participant's Baseline total score was average of nighttime total symptom score on day of randomization and 3 highest scores calculated for 6 days immediately prior to day of randomization. Each participant's average change from Baseline nighttime total symptom score for Weeks 1-2 was the participant's average Nighttime total symptom score over the treatment period minus the participant's Baseline score.
Time Frame	Baseline (Day 1) and up to 2 Weeks

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	312	312	309
TNSS	-2.5 (0.13)	-3.7 (0.14)	-2.7 (0.13)
Nasal congestion	-0.6 (0.03)	-0.9 (0.04)	-0.7 (0.03)
Itchy nose	-0.7 (0.04)	-0.9 (0.04)	-0.7 (0.04)
Runny nose	-0.6 (0.04)	-0.9 (0.04)	-0.7 (0.03)
Sneezing	-0.7 (0.04)	-1.0 (0.04)	-0.7 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -1.6 to -0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.136
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

3. Secondary Outcome

Title	Mean Change From Baseline Over the Two-week Treatment Period in D-rTNSS
Description	The Daytime reflective assessments were recorded each evening and assessed 4 nasal symptoms (rhinorrhea, nasal congestion, nasal itching, and sneezing) at evening and night using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). The scores of each of the four Daytime symptoms were summed for each participant to create a D-rTNSS for each day. The total score ranged from 0 (best) to 12 (worst). Each participant's Baseline total symptom score was the average of the four highest total symptom score calculated for the seven days immediately prior to the day of randomization. Each participant's average change from Baseline Daytime total symptom score for Weeks 1-2 was the participant's average Daytime total symptom score over the treatment period minus the participants Baseline score.
Time Frame	Baseline (Day 1) and up to 2 Weeks

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	312	312	309
TNSS	-2.6 (0.13)	-3.7 (0.14)	-3.0 (0.13)
Nasal congestion	-0.7 (0.04)	-0.9 (0.04)	-0.8 (0.03)
Itchy nose	-0.7 (0.04)	-1.0 (0.04)	-0.8 (0.04)
Runny nose	-0.6 (0.04)	-0.9 (0.04)	-0.7 (0.03)
Sneezing	-0.7 (0.04)	-1.1 (0.04)	-0.9 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -1.5 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.136
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

4. Secondary Outcome

Title	Mean Change From Baseline Over the Two-week Treatment Period in 24-hour Reflective Total Nasal Symptom Scores (24-hour rTNSS) and Component Nasal Score
Description	Daily 24-hour rTNSS was calculated as the average of the corresponding N-rTNSS and D-rTNSS using a 4-point scale where, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). The total score ranged from 0 (best) to 12 (worst). The 24-hour total symptom score for a Day is the average of the daytime total symptom score for that Day and the nighttime score for (D+1). If either component of a given date's 24-hour total symptom score was missing, then the 24-hour total symptom score itself were to be set to missing. Each participant's average change from Baseline 24-hour total symptom score for Weeks 1-2 was the participants average 24-hour total symptom score over the treatment period minus the participant's Baseline score.
Time Frame	Baseline (Day 1) and up to 2 Weeks

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	312	312	308
TNSS	-2.5 (0.13)	-3.6 (0.14)	-2.8 (0.13)
Nasal congestion	-0.6 (0.03)	-0.9 (0.04)	-0.7 (0.03)
Itchy nose	-0.7 (0.04)	-0.9 (0.04)	-0.8 (0.04)
Runny nose	-0.6 (0.03)	-0.9 (0.04)	-0.7 (0.03)
Sneezing	-0.7 (0.04)	-1.0 (0.04)	-0.8 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -1.6 to -0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -1.3 to -0.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.136
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

5. Secondary Outcome

Title	Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Ocular Symptom Scores (N-rTOSS)
Description	The nighttime reflective assessments were recorded each morning and assessed 3 ocular symptoms (tearing/watering, itching/burning, and redness) at evening and night using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). Scores of each of 3 Nighttime symptoms were summed for each participant to create a N-rTOSS for each day. The total score ranged from 0 (best) to 9 (worst). Each participants Baseline total score was average of nighttime total symptom score on day of randomization and the 3 highest scores calculated for 6 days immediately prior to the day of randomization. Each participant's average change from Baseline nighttime total symptom score for Weeks 1-2 was the participant's average Nighttime total symptom score over treatment period minus the participant's Baseline score.
Time Frame	Baseline (Day 1) and up to 2 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	312	312	309
TOSS	-2 (0.11)	-2.5 (0.11)	-2.2 (0.11)
Eye tearing	-0.7 (0.04)	-0.9 (0.04)	-0.8 (0.04)
Eye itching	-0.7 (0.04)	-0.9 (0.04)	-0.8 (0.04)
Eye redness	-0.6 (0.04)	-0.8 (0.04)	-0.7 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.8 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.106
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.286
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

6. Secondary Outcome

Title	Mean Change From Baseline Over the Two-week Treatment Period in Daytime Reflective Total Ocular Symptom Scores (D-rTOSS)
Description	The Daytime reflective assessments were recorded each evening and assessed the 3 nasal symptoms (tearing/watering, itching/burning, and redness) at evening and night using a 4-point scale where, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). The scores of each of the three Daytime symptoms were summed for each participant to create a D-rTOSS for each day. The total score ranged from 0 (best) to 9 (worst). Each participants Baseline total symptom score was the average of the four highest total symptom score calculated for the seven days immediately prior to the day of randomization. Each participant's average change from Baseline Daytime total symptom score for Weeks 1-2 was the participant's average Daytime total symptom score over the treatment period minus the participant's Baseline score.
Time Frame	Baseline (Day 1) and up to 2 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	312	312	309
TOSS	-2.2 (0.11)	-2.6 (0.11)	-2.4 (0.11)
Eye tearing	-0.8 (0.04)	-0.9 (0.04)	-0.8 (0.04)
Eye itching	-0.8 (0.04)	-0.9 (0.04)	-0.9 (0.04)
Eye redness	-0.7 (0.04)	-0.8 (0.04)	-0.7 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -0.7 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.286
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.106
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

7. Secondary Outcome

Title	Mean Change From Baseline Over the Two-week Treatment Period in 24-hour Reflective Total Ocular Symptom Scores (24-hour rTOSS)
Description	Daily 24-hour rTOSS was calculated as the average of the corresponding N-rTOSS and D-rTOSS using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). The total score ranged from 0 (best) to 9 (worst). The 24-hour total symptom score for a Day is the average of the daytime total symptom score for that Day and the nighttime score for (D+1). If either component of a given date's 24-hour total symptom score was missing, then the 24-hour total symptom score itself was to be set to missing. Each participant's average change from Baseline 24-hour total symptom score for Weeks 1-2 was the participant's average 24-hour total symptom score over the treatment period minus the participant's Baseline score. Baseline is the 4 highest scores calculated for the 7 days prior to Day 1.
Time Frame	Baseline (Day 1) and up to 2 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	312	312	308
TOSS	-2.0 (0.11)	-2.5 (0.11)	-2.2 (0.11)
Eye tearing	-0.7 (0.04)	-0.9 (0.04)	-0.8 (0.04)
Eye itching	-0.7 (0.04)	-0.9 (0.04)	-0.8 (0.04)
Eye redness	-0.7 (0.04)	-0.8 (0.04)	-0.7 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.7 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.286
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.106
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

8. Secondary Outcome

Title	Mean Change From Baseline Over the Two-week Treatment Period in Pre-dose Instantaneous Total Nasal Symptom Score (Pre-dose iTNSS) and Pre-dose Instantaneous Total Ocular Symptom Scores (Pre-dose iTOSS)
Description	Participants were instructed to score and document their symptoms in an instantaneous manner on a diary card. The instantaneous rating was performed once daily just prior to administering their morning dose. The scores of each of the instantaneous nasal symptoms (nasal congestion, itching, rhinorrhea, and sneezing) and ocular symptoms (tearing/watering, itching/burning, and redness) were summed for each participant to create a iTNSS and iTOSS, respectively using a 4-point scale, 0- 'None' (symptom is not present), 1- 'Mild' (sign/symptom present; easily tolerated), 2- 'Moderate' (sign/symptom bothersome but tolerable), 3- 'Severe' (sign/symptom hard to tolerate; interference with activities of daily living). Total score ranged from 0 (best) to 12 (worst) for iTNSS and 0 (best) to 9 (worst) for iTOSS. Each participant's average change from Baseline iTNSS and iTOSS was participant's average iTNSS and iTOSS total score over the treatment period minus the participant's Baseline score.
Time Frame	Baseline (Day 1) and up to 2 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	312	312	309
TNSS	-2.3 (0.13)	-3.6 (0.14)	-2.6 (0.12)
Pre-dose iTNSS, Nasal congestion	-0.6 (0.03)	-0.8 (0.03)	-0.6 (0.03)
Pre-dose iTNSS, Itchy nose	-0.7 (0.04)	-1.0 (0.04)	-0.7 (0.04)
Pre-dose iTNSS, Runny nose	-0.6 (0.04)	-0.9 (0.04)	-0.6 (0.04)
Pre-dose iTNSS, Sneezing	-0.7 (0.04)	-1.0 (0.04)	-0.7 (0.04)
TOSS	-1.9 (0.11)	-2.4 (0.12)	-2.2 (0.1)
Pre-dose iTOSS, Eye tearing	-0.7 (0.04)	-0.9 (0.04)	-0.8 (0.04)
Pre-dose iTOSS, Eye itching	-0.7 (0.04)	-0.9 (0.04)	-0.8 (0.04)
Pre-dose iTOSS, Eye redness	-0.6 (0.04)	-0.8 (0.04)	-0.7 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments	Pre-dose iTNSS
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -1.7 to -1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments	Pre-dose iTNSS
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -1.4 to -0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments	Pre-dose iTNSS
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.193
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments	Pre-dose iTOSS
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.8 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments	Pre-dose iTOSS
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.058
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments	Pre-dose iTOSS
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.5 to 0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

9. Secondary Outcome

Title	Mean Change From Baseline Over the Two-week Treatment Period in Peak NasalIinspiratory Flow (PNIF)
Description	PNIF was measured by participants using an In-Check Nasal portable hand-held inspiratory flow meter and face mask. Participants recorded PNIF twice daily (in the morning prior to taking their study medication and in the evening). Three measurements were taken on each occasion and the highest measurement recorded on the electronic diary. Each participant's average change from Baseline PNIF was the participant's average PNIF over the treatment period minus the participant's baseline PNIF.
Time Frame	Baseline (Day 1) and up to 2 Weeks

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	313	312	311
Morning PNIF	1.7 (0.99)	9.9 (1.28)	1.4 (1.18)
Evening PNIF	0.2 (1.12)	7.1 (1.31)	1.3 (1.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments	Morning assessment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.8
	Confidence Interval	(2-Sided) 95%; 5.7 to 11.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.59
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments	Morning assessment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	8.4
	Confidence Interval	(2-Sided) 95%; 5.3 to 11.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.59
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments	Morning assessment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.779
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -3.6 to 2.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.59
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments	Evening assessment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.3
	Confidence Interval	(2-Sided) 95%; 3.1 to 9.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.65
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments	Evening assessment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7
	Confidence Interval	(2-Sided) 95%; 3.8 to 10.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.65
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments	Evening assessment
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.662
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -2.5 to 4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.65
	Estimation Comments

10. Secondary Outcome

Title	Mean Change From Baseline for Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ)
Description	The NRQLQ is a paper instrument administered on the day of randomization and at Visit 4/Early Withdrawal to assess nocturnal rhinitis-related quality of life. The NRQLQ is a 16-item, self-administered, disease-specific (allergic rhinitis), and quality of life instrument that measures the functional problems most troublesome to patients with nocturnal allergy symptoms over a one-week interval. Each question is scored from 0 to 6 with higher scores indicating more nocturnal impairment. Items are grouped into four domains: Sleep problems, Sleep time problems, Symptoms on waking in the morning and Practical problems. An overall score was calculated from the mean score of all items. Each participant's average change from Baseline NRQLQ score was the participant's average NRQLQ score over the treatment period minus the participant's baseline score.
Time Frame	Baseline (Day 1) and Day 15

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	Placebo	FFNS 110 mcg	Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
Measure Participants	313	312	311
Overall score	-1.3 (0.08)	-1.9 (0.09)	-1.5 (0.08)
Sleep problems	-1.2 (0.09)	-1.9 (0.09)	-1.5 (0.09)
Sleep time problems	-1.3 (0.09)	-1.9 (0.09)	-1.5 (0.09)
Symptoms on waking	-1.4 (0.09)	-2 (0.1)	-1.5 (0.09)
Practical problems	-1.2 (0.09)	-1.9 (0.1)	-1.6 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FFNS 110 mcg, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.7 to -0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Fex 180 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.203
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, FFNS 110 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -0.8 to -0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Adverse Events

Time Frame	Adverse events (AEs) and Serious adverse events (SAEs) were collected from the time the first dose of study medication until the follow up contact (Up to Day 20)
Adverse Event Reporting Description	SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants randomized to double-blind treatment.
Arm/Group Title	Placebo		FFNS 110 mcg		Fex 180 mg
Arm/Group Description	Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.		Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.		Participants received oral capsule (overencapsulated Fex 180 mg oral tablet) and vehicle placebo nasal spray each morning once daily for two weeks following pre-dose symptom assessment.
All Cause Mortality
	Placebo		FFNS 110 mcg		Fex 180 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/313 (0%)		0/312 (0%)		0/311 (0%)
Serious Adverse Events
	Placebo		FFNS 110 mcg		Fex 180 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/313 (0%)		0/312 (0%)		1/311 (0.3%)
Hepatobiliary disorders
Cholecystitis	0/313 (0%)		0/312 (0%)		1/311 (0.3%)
Other (Not Including Serious) Adverse Events
	Placebo		FFNS 110 mcg		Fex 180 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/313 (3.5%)		12/312 (3.8%)		10/311 (3.2%)
Nervous system disorders
Headache	11/313 (3.5%)		12/312 (3.8%)		10/311 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.