Trial Outcomes & Findings for A Phase IIA FF/VI Study to Measure FeNO in Asthmatic Patients. (NCT NCT02712047)

NCT ID: NCT02712047

Last Updated: 2018-08-28

Results Overview

FeNO is non-invasive marker of airway inflammation in asthma participants. It was measured by the participants, using Niox Vero device at AM (pre-dose) and PM on Day -7 and all way through Day 29 of each TP. The FeNO measurements were done over time following stop of repeat dose treatment with FF/VI. Change from Baseline was measured as ratio of post-dose visit value to Baseline value. Baseline was defined as Day 1(Pre-dose). Subject level Baseline defined as the mean of Baseline across periods for each participant. Period level Baseline defined as the difference between the Baseline and subject level Baseline for each period and each participant. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Summary of ratio from Baseline for exhaled nitric oxide reported as Geometric mean and Geometric coefficient of Variation. NA indicates data was not available.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Baseline and up to Day 29 in each treatment period

Results posted on

2018-08-28

Participant Flow

This was a randomized, double blind, placebo-controlled, two-period, crossover repeat dose study in adult participants with asthma. The study was conducted from 29 April 2016 to 21 February 2017, at a single site in New Zealand.

Total 36 participants were screened, of which 8 participants were screen failures. Of the 28 participants who were enrolled in the study, 27 participants were randomized as 1 participant withdrew before randomization. The study had Run-in period of 7 days, which was followed by a Treatment period (TP) 1, a wash-out period of 21 days and TP2.

Participant milestones

Participant milestones
Measure	Fluticasone Furoate/Vilanterol (FF/VI) Followed by Placebo Participants were administered with FF/VI 100/25 microgram (mcg) during TP 1 followed by matching Placebo during TP 2 through a dry powder inhaler (DPI) once daily each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.	Placebo Followed by FF/VI Participants were administered with Placebo during TP 1 followed by FF/VI 100/25 mcg during TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.
Treatment Period 1 (35 Days) STARTED	14	13
Treatment Period 1 (35 Days) COMPLETED	14	13
Treatment Period 1 (35 Days) NOT COMPLETED	0	0
Washout Period (21 Days) STARTED	14	13
Washout Period (21 Days) COMPLETED	14	13
Washout Period (21 Days) NOT COMPLETED	0	0
Treatment Period 2 (35 Days) STARTED	14	13
Treatment Period 2 (35 Days) COMPLETED	14	13
Treatment Period 2 (35 Days) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase IIA FF/VI Study to Measure FeNO in Asthmatic Patients.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total (Placebo+FF/VI 100/25mcg) n=27 Participants In this two-period crossover study, participants received FF/VI 100/25 mcg or matching placebo through DPI once daily in each morning for 14 days either in TP 1 or TP 2 as per randomization schedule. There was a 21-days monitoring/washout period between two treatments during which participants were allowed to take rescue medication if required. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.
Age, Continuous	24.5 Years STANDARD_DEVIATION 8.14 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Race/Ethnicity, Customized White	21 Participants n=5 Participants
Race/Ethnicity, Customized Asian and White	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiin or other Pacific Islander and White	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and up to Day 29 in each treatment period

Population: The Pharmacodynamic (PD) Population consisted of all the participants from the All Subject population who had at least one PD assessment.

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Day 29 in each treatment period

Population: PD Population.

In participants with asthma the FeNO is a non-invasive marker of airway inflammation. The FeNO was measured by the participants AM (pre-dose) and PM on Day -7 and all the way through Day 29 of each treatment period. The measurements were recorded using Niox Vero device provided at the site. These FeNO measurements were done throughout the treatment period. Change from Baseline was measured by the value at post-dose visit minus the Baseline value. Baseline was defined as Day 1(Pre-dose). Subject level Baseline is defined as the mean of Baseline across periods for each participant. Period level Baseline is defined as the difference between the Baseline and subject level Baseline for each period and each participant. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data was not available.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Participants received matching Placebo in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.	FF/VI 100/25mcg n=27 Participants Participants received FF/VI 100/25 mcg in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 1, AM (n=27,27)	1.9 Parts per billion Standard Deviation 24.39	-63.3 Parts per billion Standard Deviation 45.47
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 1, PM (n=27,27)	-0.5 Parts per billion Standard Deviation 24.55	-68.5 Parts per billion Standard Deviation 49.07
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 2, AM (n=27,27)	1.3 Parts per billion Standard Deviation 27.67	-63.5 Parts per billion Standard Deviation 53.63
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 4, PM (n=27,27)	-11.6 Parts per billion Standard Deviation 17.93	-51.5 Parts per billion Standard Deviation 42.12
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 5, AM (n=27,27)	-15.3 Parts per billion Standard Deviation 22.49	-48.9 Parts per billion Standard Deviation 47.09
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 5, PM (n=26,26)	-22.1 Parts per billion Standard Deviation 19.45	-54.0 Parts per billion Standard Deviation 45.00
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 6, AM (n=26,26)	-17.6 Parts per billion Standard Deviation 24.37	-47.1 Parts per billion Standard Deviation 42.19
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 6, PM (n=24,26)	-19.4 Parts per billion Standard Deviation 25.76	-54.0 Parts per billion Standard Deviation 43.96
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 10, AM (n=24,26)	4.1 Parts per billion Standard Deviation 27.86	-31.6 Parts per billion Standard Deviation 31.50
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 11, AM (n=26,26)	12.8 Parts per billion Standard Deviation 31.82	-23.8 Parts per billion Standard Deviation 39.65
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 11, PM (n=27,27)	6.2 Parts per billion Standard Deviation 34.03	-26.4 Parts per billion Standard Deviation 41.33
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 12, AM (n=27,27)	3.1 Parts per billion Standard Deviation 24.79	-25.7 Parts per billion Standard Deviation 36.64
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 12, PM (n=27,27)	1.3 Parts per billion Standard Deviation 25.08	-29.4 Parts per billion Standard Deviation 37.19
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 13, AM (n=27,25)	8.3 Parts per billion Standard Deviation 35.47	-23.3 Parts per billion Standard Deviation 30.09
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 14, AM (n=26,27)	4.7 Parts per billion Standard Deviation 45.42	-23.5 Parts per billion Standard Deviation 38.84
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 15, AM (n=26,26)	-1.6 Parts per billion Standard Deviation 47.88	-25.8 Parts per billion Standard Deviation 37.76
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 17, AM (n=25,26)	6.1 Parts per billion Standard Deviation 42.81	-20.9 Parts per billion Standard Deviation 39.31
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 2, PM (n=27,27)	-3.1 Parts per billion Standard Deviation 24.64	-66.1 Parts per billion Standard Deviation 48.26
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 3, AM (n=27,27)	-0.8 Parts per billion Standard Deviation 25.07	-56.6 Parts per billion Standard Deviation 53.97
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 3, PM (n=27,27)	-7.9 Parts per billion Standard Deviation 21.18	-59.8 Parts per billion Standard Deviation 47.32
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 4, AM (n=27,27)	1.2 Parts per billion Standard Deviation 33.27	-48.6 Parts per billion Standard Deviation 50.54
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 7, AM (n=27,27)	-15.4 Parts per billion Standard Deviation 24.26	-50.0 Parts per billion Standard Deviation 43.19
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 7, PM (n=25,25)	-19.9 Parts per billion Standard Deviation 25.92	-46.4 Parts per billion Standard Deviation 42.73
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 8, AM (n=25,27)	-14.2 Parts per billion Standard Deviation 30.00	-42.7 Parts per billion Standard Deviation 44.14
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 8, PM (n=27,26)	-15.3 Parts per billion Standard Deviation 24.70	-46.1 Parts per billion Standard Deviation 40.39
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 9, AM (n=27,27)	-5.7 Parts per billion Standard Deviation 29.23	-40.1 Parts per billion Standard Deviation 37.45
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 9, PM (n=27,27)	-5.3 Parts per billion Standard Deviation 23.53	-38.7 Parts per billion Standard Deviation 40.36
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 10, PM (n=27,27)	3.8 Parts per billion Standard Deviation 28.99	-32.8 Parts per billion Standard Deviation 37.47
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 13, PM (n=25,25)	-1.6 Parts per billion Standard Deviation 38.12	-26.2 Parts per billion Standard Deviation 39.97
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 14, PM (n=25,26)	-3.4 Parts per billion Standard Deviation 42.26	-30.9 Parts per billion Standard Deviation 43.69
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 15, PM (n=25,25)	-3.7 Parts per billion Standard Deviation 49.33	-27.9 Parts per billion Standard Deviation 43.14
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 16, AM (n=26,27)	3.7 Parts per billion Standard Deviation 48.00	-26.7 Parts per billion Standard Deviation 43.16
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 16, PM (n=26,27)	4.5 Parts per billion Standard Deviation 37.40	-26.6 Parts per billion Standard Deviation 43.37
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 17, PM (n=18,16)	-8.5 Parts per billion Standard Deviation 29.54	-19.6 Parts per billion Standard Deviation 48.58
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 18, AM (n=17,14)	-7.5 Parts per billion Standard Deviation 32.10	-27.3 Parts per billion Standard Deviation 44.36
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 18, PM (n=14,10)	-6.2 Parts per billion Standard Deviation 23.93	-38.3 Parts per billion Standard Deviation 42.90
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 19, AM (n=14,10)	-2.8 Parts per billion Standard Deviation 27.47	-30.7 Parts per billion Standard Deviation 50.03
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 19, PM (n=12,6)	-9.3 Parts per billion Standard Deviation 24.19	-52.2 Parts per billion Standard Deviation 49.82
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 20, AM (n=12,6)	0.1 Parts per billion Standard Deviation 27.71	-40.2 Parts per billion Standard Deviation 46.27
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 20, PM (n=7,5)	-8.7 Parts per billion Standard Deviation 21.68	-59.0 Parts per billion Standard Deviation 63.82
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 21, AM (n=7,6)	-6.6 Parts per billion Standard Deviation 24.08	-32.7 Parts per billion Standard Deviation 56.23
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 21, PM (n=7,5)	-3.0 Parts per billion Standard Deviation 25.83	-51.2 Parts per billion Standard Deviation 58.37
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 22, AM (n=6,5)	-7.5 Parts per billion Standard Deviation 27.54	-37.0 Parts per billion Standard Deviation 66.25
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 22, PM (n=6,5)	-11.5 Parts per billion Standard Deviation 27.52	-51.8 Parts per billion Standard Deviation 63.96
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 23, AM (n=7,5)	-0.6 Parts per billion Standard Deviation 29.53	-37.0 Parts per billion Standard Deviation 71.04
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 23, PM (n=2,1)	-0.5 Parts per billion Standard Deviation 54.45	0.0 Parts per billion Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 24, AM (n=2,1)	2.0 Parts per billion Standard Deviation 59.40	13.0 Parts per billion Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 24, PM (n=1,1)	-24.0 Parts per billion Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.	-8.0 Parts per billion Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 25, AM (n=1,0)	-33.0 Parts per billion Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.	—
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 26, PM (n=0,1)	—	-1.0 Parts per billion Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 28, AM (n=0,1)	—	4.0 Parts per billion Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 28, PM (n=0,1)	—	-21.0 Parts per billion Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.
Change From Baseline in FeNO Over the FF/VI Treatment Period Day 29, AM (n=0,1)	—	-8.0 Parts per billion Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.

SECONDARY outcome

Timeframe: Baseline and up to Day 29 in TP1; Baseline and up to follow up (Day 29) in TP2

Population: PD population.

The PEF is a lung function evaluation assessed using a PEF meter. It was defined as the maximum amount of air exhaled during forced exhalation with lungs fully inflated. For PEF measurements the best of the 3 recordings were recorded AM and PM (i.e every 12 hours), from Day-7 through to Day 29 of TP1, and then from Day 1 of TP2 through to the (29). Change from Baseline was measured by the value at post-dose visit minus the Baseline value. Baseline was defined as Day 1(Pre-dose). Subject level Baseline is defined as the mean of Baseline across periods for each participant. Period level Baseline is defined as the difference between the Baseline and subject level Baseline for each period and each participant. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data was not available.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Participants received matching Placebo in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.	FF/VI 100/25mcg n=27 Participants Participants received FF/VI 100/25 mcg in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 17, PM (n=18,16)	10.6 Liter per minute Standard Deviation 86.60	8.7 Liter per minute Standard Deviation 62.33
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 18, AM (n=17,14)	-14.2 Liter per minute Standard Deviation 79.96	3.8 Liter per minute Standard Deviation 71.50
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 18, PM (n=14,10)	-8.9 Liter per minute Standard Deviation 90.25	29.6 Liter per minute Standard Deviation 64.62
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 19, AM (n=14,10)	-11.4 Liter per minute Standard Deviation 91.61	-0.1 Liter per minute Standard Deviation 70.24
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 19, PM (n=12,6)	2.3 Liter per minute Standard Deviation 102.76	27.7 Liter per minute Standard Deviation 61.49
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 20, AM (n=12,6)	-8.5 Liter per minute Standard Deviation 81.09	-10.5 Liter per minute Standard Deviation 71.92
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 20, PM (n=7,5)	-27.7 Liter per minute Standard Deviation 46.03	26.6 Liter per minute Standard Deviation 49.22
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 21, AM (n=7,6)	-43.3 Liter per minute Standard Deviation 56.85	17.8 Liter per minute Standard Deviation 78.20
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 21, PM (n=6,4)	-16.7 Liter per minute Standard Deviation 73.86	-19.8 Liter per minute Standard Deviation 32.62
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 22, AM (n=5,5)	-48.4 Liter per minute Standard Deviation 40.28	-11.0 Liter per minute Standard Deviation 103.22
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 22, PM (n=6,5)	-56.8 Liter per minute Standard Deviation 46.23	-2.0 Liter per minute Standard Deviation 91.29
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 23, AM (n=6,5)	-15.0 Liter per minute Standard Deviation 50.62	11.4 Liter per minute Standard Deviation 53.62
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 23, PM (n=2,1)	-53.0 Liter per minute Standard Deviation 1.41	1.0 Liter per minute Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 24, AM (n=2,1)	-23.0 Liter per minute Standard Deviation 25.46	74.0 Liter per minute Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 24, PM (n=1,1)	-50.0 Liter per minute Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed	15.0 Liter per minute Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 25, AM (n=1,0)	-31.0 Liter per minute Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed	—
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 26, PM (n=0,1)	—	-62.0 Liter per minute Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 27, AM (n=0,1)	—	82.0 Liter per minute Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 28, AM (n=0,1)	—	-42.0 Liter per minute Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 29, AM (n=0,1)	—	6.0 Liter per minute Standard Deviation NA Standard deviation could not be computed as a single participant was analyzed.
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 6, PM (n=24,26)	11.3 Liter per minute Standard Deviation 75.26	28.5 Liter per minute Standard Deviation 52.75
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 1, AM (n=27,27)	-1.0 Liter per minute Standard Deviation 67.11	44.6 Liter per minute Standard Deviation 55.54
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 1, PM (n=27,27)	17.4 Liter per minute Standard Deviation 69.59	54.5 Liter per minute Standard Deviation 63.23
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 2, AM (n=27,27)	5.1 Liter per minute Standard Deviation 61.50	32.4 Liter per minute Standard Deviation 55.35
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 2, PM (n=27,27)	16.6 Liter per minute Standard Deviation 74.02	37.2 Liter per minute Standard Deviation 53.42
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 3, AM (n=27,27)	9.0 Liter per minute Standard Deviation 58.49	24.3 Liter per minute Standard Deviation 58.56
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 3, PM (n=27,27)	20.4 Liter per minute Standard Deviation 69.10	47.3 Liter per minute Standard Deviation 52.80
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 4, AM (n=26,26)	18.3 Liter per minute Standard Deviation 61.63	28.8 Liter per minute Standard Deviation 54.42
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 4, PM (n=27,27)	36.0 Liter per minute Standard Deviation 85.62	43.9 Liter per minute Standard Deviation 56.01
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 5, AM (n=27,26)	19.7 Liter per minute Standard Deviation 61.28	25.4 Liter per minute Standard Deviation 49.86
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 5, PM (n=26,27)	21.5 Liter per minute Standard Deviation 75.94	30.9 Liter per minute Standard Deviation 49.67
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 6, AM (n=25,26)	-0.4 Liter per minute Standard Deviation 69.89	4.1 Liter per minute Standard Deviation 61.63
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 7, AM (n=27,27)	11.5 Liter per minute Standard Deviation 71.97	17.0 Liter per minute Standard Deviation 55.89
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 7, PM (n=24,26)	11.8 Liter per minute Standard Deviation 75.33	21.8 Liter per minute Standard Deviation 55.70
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 8, AM (n=27,27)	-1.6 Liter per minute Standard Deviation 73.80	2.6 Liter per minute Standard Deviation 51.94
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 8, PM (n=27,27)	13.1 Liter per minute Standard Deviation 61.79	9.1 Liter per minute Standard Deviation 56.68
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 9, AM (n=27,26)	-7.2 Liter per minute Standard Deviation 80.69	-14.7 Liter per minute Standard Deviation 74.06
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 9, PM (n=27,27)	9.1 Liter per minute Standard Deviation 73.71	-1.7 Liter per minute Standard Deviation 58.12
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 10, AM (n=26,26)	-19.6 Liter per minute Standard Deviation 76.63	-19.9 Liter per minute Standard Deviation 68.55
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 10, PM (n=27,26)	-1.7 Liter per minute Standard Deviation 84.64	12.6 Liter per minute Standard Deviation 52.16
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 11, AM (n=26,27)	-12.8 Liter per minute Standard Deviation 74.84	-12.3 Liter per minute Standard Deviation 56.24
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 11, PM (n=27,27)	15.8 Liter per minute Standard Deviation 76.76	-7.3 Liter per minute Standard Deviation 63.12
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 12, AM (n=24,26)	-11.0 Liter per minute Standard Deviation 83.14	-23.5 Liter per minute Standard Deviation 64.35
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 12, PM (n=26,27)	-2.4 Liter per minute Standard Deviation 71.17	-5.9 Liter per minute Standard Deviation 66.19
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 13, AM (n=27,26)	-20.6 Liter per minute Standard Deviation 77.50	-35.1 Liter per minute Standard Deviation 67.19
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 13, PM (n=25,26)	17.0 Liter per minute Standard Deviation 104.76	-13.0 Liter per minute Standard Deviation 61.78
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 14, AM (n=25,25)	-31.5 Liter per minute Standard Deviation 77.48	-13.6 Liter per minute Standard Deviation 65.25
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 14, PM (n=25,27)	-0.8 Liter per minute Standard Deviation 76.69	-1.6 Liter per minute Standard Deviation 58.26
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 15, AM (n=25,27)	-17.4 Liter per minute Standard Deviation 59.88	-20.4 Liter per minute Standard Deviation 58.86
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 15, PM (n=25,25)	-15.0 Liter per minute Standard Deviation 67.65	-7.8 Liter per minute Standard Deviation 64.72
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 16, AM (n=25,26)	-27.0 Liter per minute Standard Deviation 66.70	-30.2 Liter per minute Standard Deviation 75.78
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 16, PM (n=26,26)	-8.1 Liter per minute Standard Deviation 74.86	0.7 Liter per minute Standard Deviation 60.72
Change From Baseline in Peak Expiratory Flow (PEF) During Treatment and Following Cessation of Repeat Dose Treatment With FF/VI Day 17, AM (n=26,26)	-23.4 Liter per minute Standard Deviation 73.32	-4.7 Liter per minute Standard Deviation 65.85

SECONDARY outcome

Timeframe: Baseline every morning and evening until Day 21 of each treatment period

Population: PD Population

FEV1 is defined as the maximal amount of air which can be exhaled forcefully in one second. Three technically acceptable FEV1 measurements were made using a spirometer, and were measured on pre-dose on Day 1, taken pre-dose on Day 14 and every morning and evening until Day 19, and in the morning on Day 21. Change from Baseline was measured by the value at post-dose visit minus the Baseline value. Baseline was defined as Day 1(Pre-dose). Subject level Baseline is defined as the mean of Baseline across periods for each participant. Period level Baseline is defined as the difference between the Baseline and subject level Baseline for each period and each participant.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Participants received matching Placebo in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.	FF/VI 100/25mcg n=27 Participants Participants received FF/VI 100/25 mcg in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 1, AM	0.036 Liter Standard Deviation 0.4169	0.361 Liter Standard Deviation 0.3135
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 1, PM	0.180 Liter Standard Deviation 0.3105	0.383 Liter Standard Deviation 0.3151
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 2, AM	0.073 Liter Standard Deviation 0.3953	0.331 Liter Standard Deviation 0.2739
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 2,PM	0.200 Liter Standard Deviation 0.3902	0.369 Liter Standard Deviation 0.3166
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 3,AM	0.084 Liter Standard Deviation 0.3668	0.271 Liter Standard Deviation 0.2967
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 3,PM	0.213 Liter Standard Deviation 0.3840	0.319 Liter Standard Deviation 0.3256
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 4, AM	0.092 Liter Standard Deviation 0.3870	0.241 Liter Standard Deviation 0.2913
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 4, PM	0.221 Liter Standard Deviation 0.4187	0.301 Liter Standard Deviation 0.3163
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 5, AM	0.197 Liter Standard Deviation 0.3375	0.207 Liter Standard Deviation 0.2498
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 7, AM	0.124 Liter Standard Deviation 0.3753	0.102 Liter Standard Deviation 0.3317
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Pre-treatment and for up to 7 Days After Cessation of Repeat Dose Treatment With FF/VI Day 21, AM	0.082 Liter Standard Deviation 0.3210	0.004 Liter Standard Deviation 0.2670

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

FF/VI 100/25mcg

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

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

Measure	Placebo n=27 Participants Participants received matching Placebo in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.	FF/VI 100/25mcg n=27 Participants Participants received FF/VI 100/25 mcg in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 7, PM (n=25,25)	0.774 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 32.7473	0.487 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 49.9617
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 13, AM (n=27,25)	1.068 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 34.0090	0.744 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 38.4939
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 13, PM (n=25,25)	0.955 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 40.2945	0.739 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 39.5506
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 14, AM (n=26,27)	1.008 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 45.5319	0.770 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 43.7613
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 15, PM (n=25,25)	0.940 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 42.3660	0.700 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 48.1949
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 16, PM (n=26,27)	1.019 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 38.1690	0.718 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 50.7656
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 18, PM (n=14,10)	0.926 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 39.2470	0.619 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 58.6249
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 19, AM (n=14,10)	1.015 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 42.2250	0.722 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 51.2962
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 21, AM (n=7,6)	0.892 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 35.8531	0.743 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 54.8750
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 21, PM (n=7,5)	0.934 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 40.4076	0.637 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 63.2223
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 24, AM (n=2,1)	0.914 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 130.0375	1.144 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation NA Standard deviation could not be computed as a single participant was analyzed.
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 25, AM (n=1,0)	0.548 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation NA Standard deviation could not be computed as a single participant was analyzed	—
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 26, PM (n=0,1)	—	0.989 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 19, PM (n=12,6)	0.911 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 30.6911	0.571 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 48.1910
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 20, AM (n=12,6)	0.958 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 43.0056	0.667 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 45.5449
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 20, PM (n=7,5)	0.828 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 39.6562	0.588 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 54.7676
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 1, AM (n=27,27)	1.042 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 31.5499	0.371 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 47.3672
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 1, PM (n=27,27)	0.985 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 26.4785	0.321 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 51.5233
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 2, AM (n=27,27)	1.012 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 27.3017	0.373 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 71.6824
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 2, PM (n=27,27)	0.957 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 26.3328	0.346 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 52.6225
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 3, AM (n=27,27)	0.987 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 24.6102	0.442 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 60.8203
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 3, PM (n=27,27)	0.922 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 23.6705	0.417 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 51.1903
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 4, AM (n=27,27)	1.007 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 34.9235	0.536 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 60.5532
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 4, PM (n=27,27)	0.857 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 23.7972	0.484 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 48.1593
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 5, AM (n=27,27)	0.834 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 24.4572	0.515 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 53.5926
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 5, PM (n=26,26)	0.734 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 27.1308	0.473 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 46.6144
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 6, AM (n=26,26)	0.794 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 31.5924	0.525 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 50.7361
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 6, PM (n=24,26)	0.783 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 30.8200	0.470 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 43.8128
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 7, AM (n=27,27)	0.826 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 31.4676	0.484 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 49.0454
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 8, AM (n=25,27)	0.830 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 40.7773	0.554 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 47.5854
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 8, PM (n=27,26)	0.834 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 30.4030	0.545 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 42.1101
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 9, AM (n=27,27)	0.935 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 35.7583	0.594 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 45.0429
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 9, PM (n=27,27)	0.924 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 32.1314	0.607 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 46.3872
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 10, AM (n=24,26)	1.022 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 34.4740	0.658 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 41.3710
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 10, PM (n=27,27)	0.989 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 35.1066	0.660 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 41.4832
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 11, AM (n=26,26)	1.092 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 37.7142	0.756 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 40.9942
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 11, PM (n=27,27)	1.029 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 28.6618	0.723 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 45.9281
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 12, AM (n=27,27)	1.028 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 29.9667	0.717 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 42.8654
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 12, PM (n=27,27)	1.004 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 28.5673	0.691 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 43.1839
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 14, PM (n=25,26)	0.955 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 45.5768	0.634 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 76.0516
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 15, AM (n=26,26)	0.977 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 51.5523	0.731 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 40.4602
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 16, AM (n=26,27)	1.029 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 51.1876	0.727 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 44.7703
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 17, AM (n=25,26)	1.049 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 40.1495	0.770 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 44.3320
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 17, PM (n=18,16)	0.967 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 38.4731	0.765 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 59.4286
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 18, AM (n=17,14)	0.935 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 39.0474	0.724 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 54.2082
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 22, AM (n=6,5)	0.845 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 45.8754	0.705 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 82.0353
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 22, PM (n=6,5)	0.822 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 43.0801	0.622 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 75.8988
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 23, AM (n=7,5)	0.925 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 51.4896	0.749 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 76.0176
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 23, PM (n=2,1)	0.898 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation 116.9108	1.000 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 24, PM (n=1,1)	0.671 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation NA Standard deviation could not be computed as a single participant was analyzed	0.911 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 28, AM (n=0,1)	—	1.044 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 28, PM (n=0,1)	—	0.767 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation NA Standard deviation could not be computed as a single participant was analyzed
Change From Baseline in Fraction of Exhaled Nitric Oxide (FeNO) Over Time Following the Cessation of Repeat Dose Treatment With FF/VI Day 29, AM (n=0,1)	—	0.911 Ratio of exhaled Nitric Oxide Geometric Coefficient of Variation NA Standard deviation could not be computed as a single participant was analyzed

Measure	Placebo n=27 participants at risk Participants received matching Placebo in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.	FF/VI 100/25mcg n=27 participants at risk Participants received FF/VI 100/25 mcg in either of TP 1 or TP 2 through DPI once daily in each morning for 14 days. There was a 21-day monitoring/washout period between two treatments in this two-period crossover study. Participants with any upper respiratory disorders including allergic rhinitis (both seasonal and perennial) and chronic rhinosinusitis (with or without nasal polyps), any participant who was on chronic maintenance therapies for these conditions were continued on their current standard of care medications (intranasal corticosteroids, antihistamines, cromones) throughout the entire duration of the study.
Infections and infestations Viral upper respiratory tract infection	18.5% 5/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	25.9% 7/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Infections and infestations Orchitis	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Infections and infestations Urinary tract infection	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Infections and infestations Viral pharyngitis	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Musculoskeletal and connective tissue disorders Back pain	7.4% 2/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	7.4% 2/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	7.4% 2/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Gastrointestinal disorders Food poisoning	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Gastrointestinal disorders Gingival pain	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Gastrointestinal disorders Nausea	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
General disorders Influenza like illness	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
General disorders Vessel puncture site pain	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Immune system disorders Food allergy	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Psychiatric disorders Insomnia	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.
Skin and subcutaneous tissue disorders Rash	0.00% 0/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.	3.7% 1/27 • All the Serious adverse events (SAEs) and Adverse events (AEs) from Day 1 to upto Day 35 in each period (Total 70 days) The 'All Subjects' population comprised of all participants randomized to the treatment who received at least one dose of study treatment, was used to assess the AEs and SAEs.