Trial Outcomes & Findings for Fluticasone Furoate Nasal Spray Versus Oral Fexofenadine (NCT NCT00435461)

NCT ID: NCT00435461

Last Updated: 2018-03-07

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 1000 participants
• Primary outcome timeframe: Baseline (Day 1) and up to 2 Weeks
• Results posted on: 2018-03-07

Participant Flow

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).

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.

Participant milestones

Measure	Placebo Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 Microgram (mcg) 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.	Fex 180 Milligram (mg) 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.
Overall Study STARTED	313	312	311
Overall Study COMPLETED	290	298	287
Overall Study NOT COMPLETED	23	14	24

Reasons for withdrawal

Measure	Placebo Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 Microgram (mcg) 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.	Fex 180 Milligram (mg) 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.
Overall Study Visit changed to EarlyWithdrawn Visit	1	0	0
Overall Study Protocol Violation	6	9	10
Overall Study Participant randomized(inadequate score)	1	0	0
Overall Study Compliance less than 80 percent	1	0	0
Overall Study In error, two study medications switched	1	0	0
Overall Study Lack of Efficacy	2	1	0
Overall Study Withdrawal by Subject	1	0	2
Overall Study Randomized in error	1	0	0
Overall Study Participant could not tolerate symptoms	0	0	1
Overall Study Participant could not swallow capsule	0	0	1
Overall Study Pregnancy	2	0	0
Overall Study Participant moved eDiary,studymedication	1	0	0
Overall Study Participant ended study one day early	1	0	0
Overall Study Noncompliance with study requirements	1	1	1
Overall Study Adverse Event	1	2	6
Overall Study Non-Compliance of diary	2	0	1
Overall Study Lost to Follow-up	1	1	2

Baseline Characteristics

Fluticasone Furoate Nasal Spray Versus Oral Fexofenadine

Baseline characteristics by cohort

Measure	Placebo n=313 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=311 Participants 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 n=936 Participants Total of all reporting groups
Age, Continuous	37.8 Years STANDARD_DEVIATION 14.39 • n=5 Participants	37.8 Years STANDARD_DEVIATION 13.95 • n=7 Participants	39.6 Years STANDARD_DEVIATION 14.63 • n=5 Participants	38.4 Years STANDARD_DEVIATION 14.34 • n=4 Participants
Sex: Female, Male Female	194 Participants n=5 Participants	209 Participants n=7 Participants	199 Participants n=5 Participants	602 Participants n=4 Participants
Sex: Female, Male Male	119 Participants n=5 Participants	103 Participants n=7 Participants	112 Participants n=5 Participants	334 Participants n=4 Participants
Race/Ethnicity, Customized African American/African Heritage	22 Participants n=5 Participants	26 Participants n=7 Participants	9 Participants n=5 Participants	57 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	7 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized White/Caucasian/European Heritage	270 Participants n=5 Participants	268 Participants n=7 Participants	286 Participants n=5 Participants	824 Participants n=4 Participants
Race/Ethnicity, Customized Mixed Race	6 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	18 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 2 Weeks

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

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.

Outcome measures

Measure	Placebo n=312 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=309 Participants 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.
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Symptoms Score (NSS) NSS, Week 1-2	-1.9 Scores on a scale Standard Error 0.1	-2.9 Scores on a scale Standard Error 0.1	-2.0 Scores on a scale Standard Error 0.09
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Symptoms Score (NSS) PMNCA, Week 1-2	-0.6 Scores on a scale Standard Error 0.03	-0.9 Scores on a scale Standard Error 0.03	-0.6 Scores on a scale Standard Error 0.03
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Symptoms Score (NSS) NANS, Week 1-2	-0.7 Scores on a scale Standard Error 0.04	-1.0 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.03
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Symptoms Score (NSS) DSNS, Week 1-2	-0.7 Scores on a scale Standard Error 0.04	-1.1 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 2 Weeks

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

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.

Outcome measures

Measure	Placebo n=312 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=309 Participants 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.
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Nasal Symptom Scores (N-rTNSS) and Component Nasal Symptoms Score TNSS	-2.5 Scores on a scale Standard Error 0.13	-3.7 Scores on a scale Standard Error 0.14	-2.7 Scores on a scale Standard Error 0.13
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Nasal Symptom Scores (N-rTNSS) and Component Nasal Symptoms Score Nasal congestion	-0.6 Scores on a scale Standard Error 0.03	-0.9 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.03
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Nasal Symptom Scores (N-rTNSS) and Component Nasal Symptoms Score Itchy nose	-0.7 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.04
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Nasal Symptom Scores (N-rTNSS) and Component Nasal Symptoms Score Runny nose	-0.6 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.03
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Nasal Symptom Scores (N-rTNSS) and Component Nasal Symptoms Score Sneezing	-0.7 Scores on a scale Standard Error 0.04	-1.0 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 2 Weeks

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

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.

Outcome measures

Measure	Placebo n=312 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=309 Participants 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.
Mean Change From Baseline Over the Two-week Treatment Period in D-rTNSS TNSS	-2.6 Scores on a scale Standard Error 0.13	-3.7 Scores on a scale Standard Error 0.14	-3.0 Scores on a scale Standard Error 0.13
Mean Change From Baseline Over the Two-week Treatment Period in D-rTNSS Nasal congestion	-0.7 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.03
Mean Change From Baseline Over the Two-week Treatment Period in D-rTNSS Itchy nose	-0.7 Scores on a scale Standard Error 0.04	-1.0 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04
Mean Change From Baseline Over the Two-week Treatment Period in D-rTNSS Runny nose	-0.6 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.03
Mean Change From Baseline Over the Two-week Treatment Period in D-rTNSS Sneezing	-0.7 Scores on a scale Standard Error 0.04	-1.1 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 2 Weeks

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

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.

Outcome measures

Measure	Placebo n=312 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=308 Participants 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.
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 TNSS	-2.5 Scores on a scale Standard Error 0.13	-3.6 Scores on a scale Standard Error 0.14	-2.8 Scores on a scale Standard Error 0.13
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 Nasal congestion	-0.6 Scores on a scale Standard Error 0.03	-0.9 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.03
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 Itchy nose	-0.7 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04
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 Runny nose	-0.6 Scores on a scale Standard Error 0.03	-0.9 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.03
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 Sneezing	-0.7 Scores on a scale Standard Error 0.04	-1.0 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 2 Weeks

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

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.

Outcome measures

Measure	Placebo n=312 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=309 Participants 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.
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Ocular Symptom Scores (N-rTOSS) TOSS	-2 Scores on a scale Standard Error 0.11	-2.5 Scores on a scale Standard Error 0.11	-2.2 Scores on a scale Standard Error 0.11
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Ocular Symptom Scores (N-rTOSS) Eye tearing	-0.7 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Ocular Symptom Scores (N-rTOSS) Eye itching	-0.7 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04
Mean Change From Baseline Over the Two-week Treatment Period in Nighttime Reflective Total Ocular Symptom Scores (N-rTOSS) Eye redness	-0.6 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 2 Weeks

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

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.

Outcome measures

Measure	Placebo n=312 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=309 Participants 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.
Mean Change From Baseline Over the Two-week Treatment Period in Daytime Reflective Total Ocular Symptom Scores (D-rTOSS) TOSS	-2.2 Scores on a scale Standard Error 0.11	-2.6 Scores on a scale Standard Error 0.11	-2.4 Scores on a scale Standard Error 0.11
Mean Change From Baseline Over the Two-week Treatment Period in Daytime Reflective Total Ocular Symptom Scores (D-rTOSS) Eye tearing	-0.8 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04
Mean Change From Baseline Over the Two-week Treatment Period in Daytime Reflective Total Ocular Symptom Scores (D-rTOSS) Eye itching	-0.8 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04
Mean Change From Baseline Over the Two-week Treatment Period in Daytime Reflective Total Ocular Symptom Scores (D-rTOSS) Eye redness	-0.7 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 2 Weeks

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

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.

Outcome measures

Measure	Placebo n=312 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=308 Participants 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.
Mean Change From Baseline Over the Two-week Treatment Period in 24-hour Reflective Total Ocular Symptom Scores (24-hour rTOSS) TOSS	-2.0 Scores on a scale Standard Error 0.11	-2.5 Scores on a scale Standard Error 0.11	-2.2 Scores on a scale Standard Error 0.11
Mean Change From Baseline Over the Two-week Treatment Period in 24-hour Reflective Total Ocular Symptom Scores (24-hour rTOSS) Eye tearing	-0.7 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04
Mean Change From Baseline Over the Two-week Treatment Period in 24-hour Reflective Total Ocular Symptom Scores (24-hour rTOSS) Eye itching	-0.7 Scores on a scale Standard Error 0.04	-0.9 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04
Mean Change From Baseline Over the Two-week Treatment Period in 24-hour Reflective Total Ocular Symptom Scores (24-hour rTOSS) Eye redness	-0.7 Scores on a scale Standard Error 0.04	-0.8 Scores on a scale Standard Error 0.04	-0.7 Scores on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 2 Weeks

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

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 2 Weeks

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

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.

Outcome measures

Measure	Placebo n=313 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=311 Participants 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.
Mean Change From Baseline Over the Two-week Treatment Period in Peak NasalIinspiratory Flow (PNIF) Morning PNIF	1.7 Liter(L)/minute (min) Standard Error 0.99	9.9 Liter(L)/minute (min) Standard Error 1.28	1.4 Liter(L)/minute (min) Standard Error 1.18
Mean Change From Baseline Over the Two-week Treatment Period in Peak NasalIinspiratory Flow (PNIF) Evening PNIF	0.2 Liter(L)/minute (min) Standard Error 1.12	7.1 Liter(L)/minute (min) Standard Error 1.31	1.3 Liter(L)/minute (min) Standard Error 1.23

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 15

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

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.

Outcome measures

Measure	Placebo n=313 Participants Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 Participants Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=311 Participants 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.
Mean Change From Baseline for Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) Overall score	-1.3 Scores on a scale Standard Error 0.08	-1.9 Scores on a scale Standard Error 0.09	-1.5 Scores on a scale Standard Error 0.08
Mean Change From Baseline for Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) Sleep problems	-1.2 Scores on a scale Standard Error 0.09	-1.9 Scores on a scale Standard Error 0.09	-1.5 Scores on a scale Standard Error 0.09
Mean Change From Baseline for Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) Sleep time problems	-1.3 Scores on a scale Standard Error 0.09	-1.9 Scores on a scale Standard Error 0.09	-1.5 Scores on a scale Standard Error 0.09
Mean Change From Baseline for Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) Symptoms on waking	-1.4 Scores on a scale Standard Error 0.09	-2 Scores on a scale Standard Error 0.1	-1.5 Scores on a scale Standard Error 0.09
Mean Change From Baseline for Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) Practical problems	-1.2 Scores on a scale Standard Error 0.09	-1.9 Scores on a scale Standard Error 0.1	-1.6 Scores on a scale Standard Error 0.1

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

FFNS 110 mcg

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Fex 180 mg

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=313 participants at risk Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 participants at risk Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=311 participants at risk 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.
Hepatobiliary disorders Cholecystitis	0.00% 0/313 • 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) SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants randomized to double-blind treatment.	0.00% 0/312 • 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) SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants randomized to double-blind treatment.	0.32% 1/311 • 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) SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants randomized to double-blind treatment.

Other adverse events

Measure	Placebo n=313 participants at risk Participants received vehicle placebo nasal spray and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	FFNS 110 mcg n=312 participants at risk Participants received FFNS 110 mcg and oral placebo capsule each morning once daily for two weeks following pre-dose symptom assessment.	Fex 180 mg n=311 participants at risk 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.
Nervous system disorders Headache	3.5% 11/313 • 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) SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants randomized to double-blind treatment.	3.8% 12/312 • 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) SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants randomized to double-blind treatment.	3.2% 10/311 • 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) SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants randomized to double-blind treatment.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER