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Clinical Trial Results:
An escalating dose, randomized, placebo-controlled incomplete block, 2-period cross-over study to assess the dose response for topical efficacy via airway responsiveness to adenosine-5'-monophosphate (AMP) challenge and the dose response for systemic activity via 24h plasma cortisol suppression and thereby the relative therapeutic index for fluticasone furoate (FF), fluticasone propionate (FP) and budesonide (BUD) in asthmatic participants.

Summary
EudraCT number	2016-003002-14
Trial protocol	GB   DE
Global end of trial date	20 Dec 2018
Results information
Results version number	v1(current)
This version publication date	19 Feb 2020
First version publication date	19 Feb 2020
Other versions

Trial information Top of page
Trial identification
Sponsor protocol code	203162
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	GlaxoSmithKline
Sponsor organisation address	980 Great West Road, Brentford, United Kingdom,
Public contact	GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
Scientific contact	GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	23 Apr 2019
Is this the analysis of the primary completion data?	No
Global end of trial reached?	Yes
Global end of trial date	20 Dec 2018
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To assess the dose response and relative potency for increasing doses of Fluticasone Furoate (FF), Fluticasone Propionate (FP) and Budesonide (BUD) in the adenosine monophosphate (AMP) challenge model at 12 hours after the last dose on Day 7. - To assess the dose response and relative potency for FF, FP and BUD on 24 hour plasma cortisol suppression on treatment from pre-dose PM dose on Day 6 to pre-dose PM dose Day 7 - To assess the therapeutic index for FF, FP and BUD.
Protection of trial subjects	Not applicable
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	09 Feb 2017
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	United Kingdom: 46
Country: Number of subjects enrolled	Germany: 10
Worldwide total number of subjects	56
EEA total number of subjects	56
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	55
From 65 to 84 years	1
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	A total of 56 participants were enrolled across 1 center in Germany and 2 centers in the United Kingdom.
Pre-assignment
Screening details	A total of 165 participants were screened of which 109 failed screening and 56 participants were enrolled in the study. Of the 56 participants enrolled, only 54 were randomized and received at least one dose of study medication.
Period 1
Period 1 title	Overall Study (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Not blinded
Arms
Arm title	Total
Arm description	Participants received Fluticasone Furoate (FF) Fluticasone Propionate, Budesonide (BUD), Placebo via inhalers ELLIPTA and DISKUS as morning (AM) and evening (PM) dose for treatment Period 1 and treatment period 2 of the study period. Washout was be a minimum of 25 days to maximum of 42 days between the two treatment periods.
Arm type	Experimental
Investigational medicinal product name	Fluticasone Propionate (FP)
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	Dry Inhalation powder 50 mcg, 100 mcg, 250 mcg, and 500 mcg per blister strip was administered using DISKUS dry powder inhaler (DPI) in both treatment periods.
Investigational medicinal product name	Fluticasone Furoate (FF)
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	Dry inhalation powder 25 mcg, 100 mcg, and 200 mcg per blister strip was administered using ELLIPTA dry powder inhaler (DPI) in both treatment periods.
Investigational medicinal product name	Budesonide (BUD)
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	Budesonide was available as white to off-white rounded granules, which disintegrated to a fine powder upon slight pressure and was administered using Turbuhaler in both treatment periods.
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Inhalation powder
Routes of administration	Inhalation use
Dosage and administration details	Lactose dry powder was administered using ELLIPTA or DISKUS in both treatment periods.
Number of subjects in period 1 [1] Total Started 54 Completed 45 Not completed 9      Consent withdrawn by subject 7      Poor Spirometry efforts 1      Lost to follow-up 1
Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Of the 56 participants enrolled, only 54 were randomized and received at least one dose of study medication.

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Overall Study
Reporting group description	-
Reporting group values Overall Study Total Number of subjects 54 54 Age Categorical Units: Participants     Total Participants 54 54 Age continuous Units: years     arithmetic mean (standard deviation) 37.9 ± 13.96 - Sex: Female, Male Units: Participants     Female 13 13     Male 41 41 Race/Ethnicity, Customized Units: Subjects     ASIAN - EAST ASIAN HERITAGE 1 1     BLACK OR AFRICAN AMERICAN 7 7     WHITE - ARABIC/NORTH AFRICAN HERITAGE 1 1     MULTIPLE 2 2     WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE 39 39     ASIAN - CENTRAL/SOUTH ASIAN HERITAGE 4 4
Subject analysis sets
Subject analysis set title	All Participants
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants in this arm received FF, FP, BUD and Placebo during the study period.
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff as total daily dose for 7 days.
Subject analysis set title	FF 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	FF 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 4 puffs PM as total daily dose for 7 days.
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 50 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 100 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 250mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 1600 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	FF 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 4 puffs PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	Fluticasone Furoate (FF)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg, 100 mcg, 200 mcg, 400 mcg, 800 mcg for 7 days.
Subject analysis set title	Fluticasone Propionate (FP)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 100 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff as total daily dose for 7 days.
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 50 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 250mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FF 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 2 puff PM as total daily dose for 7 days
Subject analysis set title	FF 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 4 puff PM as total daily dose for 7 days
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 400 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 100 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 250 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 250 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 500 mcg 2 puffs AM and 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 500 mcg 2 puffs AM and 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 1600 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 1600 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff as total daily dose for 7 days.
Subject analysis set title	FF 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	FF 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 4 puffs PM as total daily dose for 7 days.
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 50 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 100 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 250mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 1600 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	Fluticasone furoate (FF)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg, 100 mcg, 200 mcg, 400 mcg, 800 mcg PM as total daily dose for 7 days.
Subject analysis set title	Fluticasone Furoate (FF)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg, 100 mcg, 200 mcg, 400 mcg, 800 mcg PM as total daily dose for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	Fluticasone furoate (FF)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg, 100 mcg, 200 mcg, 400 mcg, 800 mcg PM as total daily dose for 7 days.
Subject analysis set title	Fluticasone Propionate (FP)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Fluticasone Propionate (FP)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Fluticasone Propionate (FP)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis sets values All Participants FF 25 mcg FF 100 mcg FF 200 mcg FF 400 mcg FF 800 mcg FP 50 mcg FP 200 mcg FP 500 mcg FP 1000 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg BUD 3200 mcg FF 800 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg Fluticasone Furoate (FF) Fluticasone Propionate (FP) FP 200 mcg Placebo FF 25 mcg FF 200 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 3200 mcg Placebo Placebo FF 25 mcg FF 25 mcg FF 100 mcg FF 100 mcg FF 200 mcg FF 200 mcg FF 400 mcg FF 800 mcg FF 400 mcg FP 50 mcg FP 50 mcg FP 200 mcg FP 200 mcg FP 500 mcg FP 500 mcg FP 1000 mcg FP 1000 mcg FP 2000 mcg FP 2000 mcg BUD 100 mcg BUD 100 mcg BUD 400 mcg BUD 400 mcg BUD 800 mcg BUD 800 mcg BUD 1600 mcg BUD 1600 mcg BUD 3200 mcg BUD 3200 mcg FF 400 mcg Placebo FF 25 mcg FF 100 mcg FF 200 mcg FF 400 mcg FF 800 mcg FP 50 mcg FP 200 mcg FP 500 mcg FP 1000 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg BUD 3200 mcg Fluticasone furoate (FF) Fluticasone Furoate (FF) Budesonide (BUD) Placebo Fluticasone furoate (FF) Fluticasone Propionate (FP) Budesonide (BUD) Fluticasone Propionate (FP) Budesonide (BUD) Fluticasone Propionate (FP) Budesonide (BUD) Budesonide (BUD) Number of subjects 54 19 19 18 18 17 20 20 18 16 17 18 18 18 18 17 18 16 16 16 51 51 19 17 20 19 21 20 18 18 12 4 14 6 13 6 13 6 12 12 6 15 6 14 6 14 6 11 6 10 6 12 4 12 5 11 5 11 5 10 5 19 17 20 19 19 18 18 21 20 20 18 17 18 18 18 18 18 14 15 12 5 6 6 6 5 6 6 6 51 Age Categorical Units: Participants     Total Participants 54 19 19 18 18 17 20 20 18 16 17 18 18 18 18 17 18 16 16 16 51 51 19 17 20 19 21 20 18 18 12 4 14 6 13 6 13 6 12 12 6 15 6 14 6 14 6 11 6 10 6 12 4 12 5 11 5 11 5 10 5 19 17 20 19 19 18 18 21 20 20 18 17 18 18 18 18 18 14 15 12 5 6 6 6 5 6 6 6 Age continuous Units: years     arithmetic mean (standard deviation) 37.9 ± 13.96 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± Sex: Female, Male Units: Participants     Female 13     Male 41 Race/Ethnicity, Customized Units: Subjects     ASIAN - EAST ASIAN HERITAGE 1     BLACK OR AFRICAN AMERICAN 7     WHITE - ARABIC/NORTH AFRICAN HERITAGE 1     MULTIPLE 2     WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE 39     ASIAN - CENTRAL/SOUTH ASIAN HERITAGE 4

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Total
Reporting group description	Participants received Fluticasone Furoate (FF) Fluticasone Propionate, Budesonide (BUD), Placebo via inhalers ELLIPTA and DISKUS as morning (AM) and evening (PM) dose for treatment Period 1 and treatment period 2 of the study period. Washout was be a minimum of 25 days to maximum of 42 days between the two treatment periods.
Subject analysis set title	All Participants
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants in this arm received FF, FP, BUD and Placebo during the study period.
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff as total daily dose for 7 days.
Subject analysis set title	FF 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	FF 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 4 puffs PM as total daily dose for 7 days.
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 50 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 100 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 250mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 1600 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	FF 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 4 puffs PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	Fluticasone Furoate (FF)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg, 100 mcg, 200 mcg, 400 mcg, 800 mcg for 7 days.
Subject analysis set title	Fluticasone Propionate (FP)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 100 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff as total daily dose for 7 days.
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 50 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 250mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FF 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 2 puff PM as total daily dose for 7 days
Subject analysis set title	FF 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 4 puff PM as total daily dose for 7 days
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 400 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mcg 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 100 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 250 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 250 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 500 mcg 2 puffs AM and 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP DISKUS 500 mcg 2 puffs AM and 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 1600 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 1600 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	FF 25 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg 1 puff as total daily dose for 7 days.
Subject analysis set title	FF 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FF 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 2 puffs PM as total daily dose for 7 days.
Subject analysis set title	FF 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 200 mcg 4 puffs PM as total daily dose for 7 days.
Subject analysis set title	FP 50 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 50 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 100 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 500 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 250mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 1000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	FP 2000 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF DISKUS 500 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 100 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 400 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 800 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 1600 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Subject analysis set title	BUD 3200 mcg
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Subject analysis set title	Fluticasone furoate (FF)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg, 100 mcg, 200 mcg, 400 mcg, 800 mcg PM as total daily dose for 7 days.
Subject analysis set title	Fluticasone Furoate (FF)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg, 100 mcg, 200 mcg, 400 mcg, 800 mcg PM as total daily dose for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Placebo
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Subject analysis set title	Fluticasone furoate (FF)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FF ELLIPTA 25 mcg, 100 mcg, 200 mcg, 400 mcg, 800 mcg PM as total daily dose for 7 days.
Subject analysis set title	Fluticasone Propionate (FP)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Fluticasone Propionate (FP)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Fluticasone Propionate (FP)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.
Subject analysis set title	Budesonide (BUD)
Subject analysis set type	Sub-group analysis
Subject analysis set description	Participants received FP ELLIPTA 50 mg, 200 mcg, 500 mcg, 1000 mcg, 2000 mcg for 7 days.

End points Top of page

Primary: Provocative concentration (PC) of adenosine 5' monophosphate (AMP) causing a 20 percent (%) reduction in forced expiratory volume in 1 second (FEV1) (AMP PC20) Top of page
End point title	Provocative concentration (PC) of adenosine 5' monophosphate (AMP) causing a 20 percent (%) reduction in forced expiratory volume in 1 second (FEV1) (AMP PC20)
End point description	The percentage fall in FEV1 was calculated using highest FEV1 (post saline) minus highest FEV1 (post AMP) divided by highest FEV1 (post saline)*100 where highest FEV1 (post saline) is the highest value of two FEV1 measurements at 60 and 180 seconds after the saline control, highest FEV1 (post AMP) is the highest value of the two FEV1 measurements at 60 and 180 seconds after the dose of AMP. Results are presented treatment wise. Pharmacodymanic (PD) population comprised of participants who were randomized and received at least one post dose of PD measurement. Only those participants with data available at the specified time points were analyzed. Mean and 95% Confidence Interval (CI) presented are predicted estimate.
End point type	Primary
End point timeframe	12 hours post last dose on Day 7
End point values FF 25 mcg FF 100 mcg FF 200 mcg FF 400 mcg FF 800 mcg FP 50 mcg FP 200 mcg FP 500 mcg FP 1000 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg BUD 3200 mcg Number of subjects analysed 19 [1] 19 [2] 18 [3] 18 [4] 17 [5] 20 [6] 20 [7] 18 [8] 16 [9] 17 [10] 18 [11] 18 [12] 18 [13] 18 [14] 17 [15] Units: Milligrams per milliliter     arithmetic mean (confidence interval 95%) 33.45 (19.10 to 58.60) 81.45 (44.65 to 148.58) 115.69 (66.82 to 200.31) 145.97 (85.02 to 250.59) 167.26 (95.36 to 293.37) 15.19 (10.80 to 21.36) 20.47 (13.94 to 30.07) 31.39 (18.88 to 52.19) 48.67 (27.30 to 86.78) 76.35 (43.21 to 134.91) 16.00 (11.41 to 22.44) 23.91 (15.08 to 37.90) 34.62 (19.28 to 62.16) 54.33 (28.40 to 103.93) 84.17 (45.48 to 155.79)
Notes [1] - Pharmacodynamic (PD) Population. [2] - PD Population. [3] - PD Population. [4] - PD Population. [5] - PD Population. [6] - PD Population. [7] - PD Population. [8] - PD Population. [9] - PD Population. [10] - PD Population. [11] - PD Population. [12] - PD Population. [13] - PD Population. [14] - PD Population. [15] - PD Population.
Statistical analysis title	Statistical Analysis 1
Comparison groups	FF 25 mcg v FF 200 mcg v FF 400 mcg v FF 800 mcg
Number of subjects included in analysis	72
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	3 parameter Emax model
Point estimate	13.5
Confidence interval
level	95%
sides	2-sided
lower limit	9.39
upper limit	19.39
Statistical analysis title	Statistical Analysis 2
Comparison groups	FF 25 mcg v FF 200 mcg v FF 400 mcg v FF 800 mcg
Number of subjects included in analysis	72
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	3 parameter Emax model
Point estimate	14.44
Confidence interval
level	95%
sides	2-sided
lower limit	8.21
upper limit	25.4
Statistical analysis title	Statistical Analysis 3
Comparison groups	FF 25 mcg v FF 200 mcg v FF 400 mcg v FF 800 mcg
Number of subjects included in analysis	72
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	3 parameter Emax model
Point estimate	48.52
Confidence interval
level	95%
sides	2-sided
lower limit	18.21
upper limit	129.32
Statistical analysis title	Statistical Analysis 4
Comparison groups	FP 50 mcg v FP 200 mcg v FP 500 mcg v FP 1000 mcg v FP 2000 mcg
Number of subjects included in analysis	91
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	3 parameter Emax model
Point estimate	13.5
Confidence interval
level	95%
sides	2-sided
lower limit	9.39
upper limit	19.39
Statistical analysis title	Statistical Analysis 5
Comparison groups	FP 50 mcg v FP 200 mcg v FP 500 mcg v FP 1000 mcg v FP 2000 mcg
Number of subjects included in analysis	91
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	3 parameter Emax model
Point estimate	14.44
Confidence interval
level	95%
sides	2-sided
lower limit	8.21
upper limit	25.4
Statistical analysis title	Statistical Analysis 6
Comparison groups	FP 50 mcg v FP 200 mcg v FP 500 mcg v FP 1000 mcg v FP 2000 mcg
Number of subjects included in analysis	91
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	3 parameter Emax model
Point estimate	1081.27
Confidence interval
level	95%
sides	2-sided
lower limit	448
upper limit	2609.66
Statistical analysis title	Statistical Analysis 7
Comparison groups	BUD 100 mcg v BUD 400 mcg v BUD 800 mcg v BUD 1600 mcg v BUD 3200 mcg
Number of subjects included in analysis	89
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	3 parameter Emax model
Point estimate	13.5
Confidence interval
level	95%
sides	2-sided
lower limit	9.39
upper limit	19.39
Statistical analysis title	Statistical Analysis 8
Comparison groups	BUD 100 mcg v BUD 400 mcg v BUD 800 mcg v BUD 1600 mcg v BUD 3200 mcg
Number of subjects included in analysis	89
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	3 parameter Emax model
Point estimate	14.44
Confidence interval
level	95%
sides	2-sided
lower limit	8.21
upper limit	25.4
Statistical analysis title	Statistical Analysis 9
Comparison groups	BUD 100 mcg v BUD 400 mcg v BUD 800 mcg v BUD 1600 mcg v BUD 3200 mcg
Number of subjects included in analysis	89
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	3 parameter Emax model
Point estimate	1467.36
Confidence interval
level	95%
sides	2-sided
lower limit	546.51
upper limit	3939.84

Primary: Provocative concentration (PC) of adenosine 5' monophosphate (AMP) causing a 20 percent (%) reduction in forced expiratory volume in 1 second (FEV1) (AMP PC20) Top of page

Primary: Cortisol Suppression 0-24 Hours Weighted Mean Top of page
End point title	Cortisol Suppression 0-24 Hours Weighted Mean
End point description	Blood samples for measurement of plasma cortisol were collected at given time point. The weighted means were derived by calculating the area under the curve (AUC) over the 0-24-hour period using the trapezoidal rule, and then dividing it by the actual time interval. Results are presented treatment wise. Only those participants with data available at the specified time points were analyzed. Mean and 95% Confidence Interval (CI) presented are predicted estimate.
End point type	Primary
End point timeframe	Pre-dose PM dose on Day 6 to pre-dose PM dose Day 7
End point values FF 25 mcg FF 100 mcg FF 200 mcg FF 400 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 800 mcg BUD 1600 mcg BUD 3200 mcg FF 800 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg FP 200 mcg Number of subjects analysed 19 [16] 19 [17] 18 [18] 18 [19] 20 [20] 18 [21] 16 [22] 18 [23] 18 [24] 17 [25] 18 [26] 16 [27] 16 [28] 16 [29] 19 [30] Units: nanomoles per liter     arithmetic mean (confidence interval 95%) 172.73 (159.88 to 186.62) 163.03 (151.01 to 176.02) 150.95 (139.48 to 163.37) 129.40 (117.82 to 142.12) 173.04 (160.15 to 186.97) 147.89 (136.59 to 160.13) 124.21 (112.88 to 136.68) 132.06 (122.05 to 142.90) 99.05 (90.24 to 108.72) 55.71 (48.26 to 64.31) 95.09 (82.26 to 109.93) 87.62 (75.37 to 101.85) 169.87 (157.23 to 183.52) 152.50 (141.26 to 164.63) 164.22 (152.11 to 177.29)
Notes [16] - PD Population. [17] - PD Population. [18] - PD Population. [19] - PD Population. [20] - PD Population. [21] - PD Population. [22] - PD Population. [23] - PD Population. [24] - PD Population. [25] - PD Population. [26] - PD Population. [27] - PD Population. [28] - PD Population. [29] - PD Population. [30] - PD Population.
Statistical analysis title	Statistical Analysis 1
Comparison groups	FF 25 mcg v FF 100 mcg v FF 200 mcg v FF 400 mcg
Number of subjects included in analysis	74
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	Exponential power-law model
Point estimate	176.09
Confidence interval
level	95%
sides	2-sided
lower limit	162.87
upper limit	190.38
Statistical analysis title	Statistical Analysis 2
Comparison groups	FF 25 mcg v FF 100 mcg v FF 200 mcg v FF 400 mcg v FF 800 mcg
Number of subjects included in analysis	92
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	exponential power-law model
Point estimate	899.99
Confidence interval
level	95%
sides	2-sided
lower limit	698.36
upper limit	1101.62
Statistical analysis title	Statistical Analysis 3
Comparison groups	FP 50 mcg v FP 200 mcg v FP 500 mcg v FP 1000 mcg v FP 2000 mcg
Number of subjects included in analysis	89
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	exponential power-law model
Point estimate	176.09
Confidence interval
level	95%
sides	2-sided
lower limit	162.87
upper limit	190.38
Statistical analysis title	Statistical Analysis 4
Comparison groups	FP 50 mcg v FP 200 mcg v FP 500 mcg v FP 1000 mcg v FP 2000 mcg
Number of subjects included in analysis	89
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	exponential power-law model
Point estimate	1986.05
Confidence interval
level	95%
sides	2-sided
lower limit	1574.7
upper limit	2397.39
Statistical analysis title	Statistical Analysis 5
Comparison groups	BUD 100 mcg v BUD 400 mcg v BUD 800 mcg v BUD 1600 mcg
Number of subjects included in analysis	68
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	exponential power-law model
Point estimate	176.09
Confidence interval
level	95%
sides	2-sided
lower limit	162.87
upper limit	190.38
Statistical analysis title	Statistical Analysis 6
Comparison groups	BUD 100 mcg v BUD 400 mcg v BUD 800 mcg v BUD 1600 mcg v BUD 3200 mcg
Number of subjects included in analysis	85
Analysis specification	Pre-specified
Analysis type
Method
Parameter type	exponential power-law model
Point estimate	1927.42
Confidence interval
level	95%
sides	2-sided
lower limit	1698.47
upper limit	2156.37

Primary: Cortisol Suppression 0-24 Hours Weighted Mean Top of page

Primary: Theraputic index of FF Top of page
End point title	Theraputic index of FF [31]
End point description	Therapeutic Index was calculated by ED20 for Cortisol Suppression 0-24 Hours Weighted Mean (nanomoles per liter[nmol/L]) divided by Dose at which 80% of the maximum effect is reached (ED80) for AMP PC20 for FF 25 mcg, FF 100 mcg, FF 200 mcg, FF 400 mcg, FF 800 mcg. Theraputic index has been presented. Only those participants with data available at the specified time points were analyzed. The timeframe mentioned is for AMP PC20 and Cortisol suppression respectively. The Estimate for ED20 Cortisol Suppression is 289.73 along with 95% CI (224.82, 354.64), the estimate for ED80 AMP PC20 is 194.09 along with 95% CI (72.82, 517.28).
End point type	Primary
End point timeframe	12 hours post-dose on Day 7, pre-dose PM dose on Day 6 to pre-dose PM dose Day 7
Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The Statistical Analysis for this endpoint is presented in the Outcomes measure description.
End point values Fluticasone Furoate (FF) Number of subjects analysed 51 [32] Units: Ratio     number (not applicable) 1.49
Notes [32] - PD Population.
No statistical analyses for this end point

Primary: Theraputic index of FF Top of page

Primary: Theraputic index of FP Top of page
End point title	Theraputic index of FP [33]
End point description	Therapeutic Index was calculated by Dose at which 20% of the maximum effect is reached (ED20) for Cortisol Suppression 0-24 Hours Weighted Mean (nanomoles per liter[nmol/L]) divided by ED80 for AMP PC20 for FP 50 mcg, FP 200 mcg, FP 500 mcg, FP 1000 mcg, FP 2000 mcg. Theraputic index has been presented. Only those participants with data available at the specified time points were analyzed. The timeframe mentioned is for AMP PC20 and Cortisol suppression respectively. The Estimate for ED20 Cortisol Suppression is 639.36 along with 95% CI (506.94, 771.79), the estimate for ED80 AMP PC20 is 4325.07 along with 95% CI (1792.02, 10438.64).
End point type	Primary
End point timeframe	12 hours post-dose on Day 7, pre-dose PM dose on Day 6 to pre-dose PM dose Day 7
Notes [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The Statistical Analysis for this endpoint is presented in the Outcomes measure description.
End point values Fluticasone Propionate (FP) Number of subjects analysed 51 [34] Units: Ratio     number (not applicable) 0.15
Notes [34] - PD Population.
No statistical analyses for this end point

Primary: Theraputic index of FP Top of page

Primary: Theraputic index of BUD Top of page
End point title	Theraputic index of BUD [35]
End point description	Therapeutic Index was calculated by ED20 for Cortisol Suppression 0-24 Hours Weighted Mean (nanomoles per liter[nmol/L]) divided by ED80 for AMP PC20 for BUD 100 mcg, BUD 400 mcg, BUD 800 mcg, BUD 1600 mcg, BUD 3200 mcg. Theraputic index has been presented. Only those participants with data available at the specified time points were analyzed. The timeframe mentioned is for AMP PC20 and Cortisol suppression respectively. The Estimate for ED20 Cortisol Suppression is 620.49 along with 95% CI (546.79, 694.20), the estimate for ED80 AMP PC20 is 5869.45 along with 95% CI (2186.03, 15759.35).
End point type	Primary
End point timeframe	12 hours post-dose on Day 7, pre-dose PM dose on Day 6 to pre-dose PM dose Day 7
Notes [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The Statistical Analysis for this endpoint is presented in the Outcomes measure description.
End point values Budesonide (BUD) Number of subjects analysed 51 [36] Units: Ratio     number (not applicable) 0.11
Notes [36] - PD Population
No statistical analyses for this end point

Primary: Theraputic index of BUD Top of page

Secondary: Number of participants with any adverse event (AE) and any serious adverse event (SAE) Top of page
End point title	Number of participants with any adverse event (AE) and any serious adverse event (SAE)
End point description	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward medical occurrence that at any dose results in death, Is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect. Results are presented treatment wise. All Subjects Population will consist of all participants who were randomized and who received at least one dose of trial medication.
End point type	Secondary
End point timeframe	Up to Week 18
End point values FF 100 mcg FF 400 mcg FP 200 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg FF 800 mcg Placebo FF 25 mcg FF 200 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 3200 mcg Number of subjects analysed 19 [37] 18 [38] 20 [39] 17 [40] 18 [41] 18 [42] 18 [43] 18 [44] 18 [45] 17 [46] 20 [47] 19 [48] 21 [49] 20 [50] 18 [51] 18 [52] Units: Participants     Any AEs 8 6 4 6 6 8 5 6 7 10 6 7 10 4 8 3     Any SAEs 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Notes [37] - All Subjects Population. [38] - All Subjects Population. [39] - All Subjects Population. [40] - All Subjects Population. [41] - All Subjects Population. [42] - All Subjects Population. [43] - All Subjects Population. [44] - All Subjects Population. [45] - All Subjects Population. [46] - All Subjects Population. [47] - All Subjects Population. [48] - All Subjects Population. [49] - All Subjects Population. [50] - All Subjects Population. [51] - All Subjects Population. [52] - All Subjects Population.
No statistical analyses for this end point

Secondary: Number of participants with any adverse event (AE) and any serious adverse event (SAE) Top of page

Secondary: Peak expiratory flow rate (PEFR) as a measure of safety and tolerability of Placebo in Period 1 Top of page
End point title	Peak expiratory flow rate (PEFR) as a measure of safety and tolerability of Placebo in Period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Participants recorded their PEFR measurement before each dose in a paper diary. Results are presented treatment wise. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
End point type	Secondary
End point timeframe	Day 2 to 8 PM, Day 9 to 14 AM and PM, Day 15 PM, Day 16 to 21 AM and PM, Day 22 PM, Day 23 to 28 AM and PM, Day 29 PM, Day 30 to 35 AM and PM in period 1
End point values Placebo Number of subjects analysed 12 Units: Liters per minute arithmetic mean (standard error)     Day 2, PM, n=12 522.5 ± 25.4     Day 3, PM, n=12 517.5 ± 27.0     Day 4, PM, n=12 514.2 ± 27.8     Day 5,PM, n=12 521.7 ± 24.2     Day 6, PM, n=12 522.5 ± 29.1     Day 7, PM, n=12 539.2 ± 32.3     Day 8, PM, n=12 530.8 ± 27.8     Day 9, AM, n=5 576.0 ± 37.5     Day 9, PM, n=12 531.3 ± 27.9     Day 10, AM, n=5 572.0 ± 34.4     Day 10, PM, n=12 535.0 ± 22.0     Day 11, AM, n=5 578.0 ± 35.9     Day 11, PM, n=12 533.8 ± 29.0     Day 12, AM, n=5 578.0 ± 37.2     Day 12 PM, n=12 527.5 ± 26.7     Day 13, AM, n=5 580.0 ± 37.4     Day 13, PM, n=12 540.8 ± 25.1     Day 14, AM, n=5 572.0 ± 34.7     Day 14, PM, n=12 543.3 ± 26.4     Day 15, PM, n=12 530.8 ± 26.0     Day 16, AM, n=5 588.0 ± 36.1     Day 16,PM, n=12 528.3 ± 24.4     Day 17, AM, n=5 586.0 ± 31.7     Day 17,PM, n=12 521.7 ± 32.5     Day 18, AM, n=5 586.0 ± 35.0     Day 18,PM, n=12 540.0 ± 26.9     Day 19, AM, n=5 568.0 ± 38.3     Day 19,PM, n=12 535.8 ± 29.3     Day 20, AM, n=5 596.0 ± 37.5     Day 20,PM, n=12 544.2 ± 28.2     Day 21, AM, n=5 580.0 ± 31.4     Day 21,PM, n=12 534.2 ± 32.6     Day 22,PM, n=11 544.5 ± 29.0     Day 23, AM, n=4 577.5 ± 37.9     Day 23,PM, n=11 530.0 ± 27.4     Day 24, AM, n=4 567.5 ± 39.4     Day 24,PM, n=11 526.4 ± 26.5     Day 25, AM, n=4 585.0 ± 39.2     Day 25,PM, n=11 530.9 ± 29.6     Day 26, AM, n=4 582.5 ± 40.0     Day 26,PM, n=11 518.2 ± 30.0     Day 27, AM, n=4 587.5 ± 40.0     Day 27,PM, n=11 539.1 ± 29.3     Day 28, AM, n=4 587.5 ± 43.0     Day 28,PM, n=10 547.0 ± 30.4     Day 29,PM, n=11 547.3 ± 28.2     Day 30, AM, n=4 567.5 ± 38.1     Day 30,PM, n=11 527.3 ± 26.6     Day 31, AM, n=4 562.5 ± 33.2     Day 31,PM, n=11 537.3 ± 26.5     Day 32, AM, n=4 582.5 ± 40.2     Day 32,PM, n=11 537.3 ± 26.2     Day 33, AM, n=4 597.5 ± 40.0     Day 33,PM, n=11 528.2 ± 30.5     Day 34, AM, n=4 580.0 ± 39.3     Day 34,PM, n=11 531.4 ± 31.9     Day 35, AM, n=4 565.0 ± 38.8     Day 35,PM, n=11 501.8 ± 26.1
No statistical analyses for this end point

Secondary: Peak expiratory flow rate (PEFR) as a measure of safety and tolerability of Placebo in Period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability of Placebo in Period 2 Top of page
End point title	PEFR as a measure of safety and tolerability of Placebo in Period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Participants recorded their PEFR measurement before each dose in a paper diary. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed (represented by n=X in the category titles). 99999 indicates standard error could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Day 2 to 8 PM, Day 9 to 14 AM and PM, Day 15 PM, Day 16 to 21 AM and PM, Day 22 PM, Day 23 to 28 AM and PM, Day 29 PM, Day 30 to 35 AM and PM in Period 2
End point values Placebo Number of subjects analysed 4 [53] Units: Liters per minute arithmetic mean (standard error)     Day 2, PM, n=4 422.5 ± 28.9     Day 3, PM, n=4 415.0 ± 27.2     Day 4, PM, n=4 398.8 ± 26.6     Day 5,PM, n=4 407.5 ± 37.5     Day 6, PM, n=4 411.3 ± 29.0     Day 7, PM, n=4 410.0 ± 36.7     Day 8, PM, n=4 415.0 ± 36.1     Day 9, AM, n=2 430.0 ± 80.0     Day 9, PM, n=4 411.3 ± 45.4     Day 10, AM, n=2 425.0 ± 65.0     Day 10, PM, n=4 403.8 ± 37.1     Day 11, AM, n=2 410.0 ± 60.0     Day 11, PM, n=4 395.0 ± 29.0     Day 12, AM, n=2 400.0 ± 50.0     Day 12, PM, n=4 398.8 ± 28.6     Day 13, AM, n=2 415.0 ± 95.0     Day 13, PM, n=4 425.0 ± 35.2     Day 14, AM, n=2 425.0 ± 65.0     Day 14, PM, n=3 420.0 ± 40.4     Day 15, PM, n=4 416.3 ± 37.0     Day 16, AM, n=2 405.0 ± 75.0     Day 16, PM, n=4 405.0 ± 32.0     Day 17, AM, n=2 390.0 ± 70.0     Day 17, PM, n=4 405.0 ± 28.9     Day 18, AM, n=1 450.0 ± 99999     Day 18, PM,n=3 423.3 ± 34.8     Day 19, AM, n=2 415.0 ± 65.0     Day 19, PM, n=4 402.5 ± 30.1     Day 20, AM, n=2 402.5 ± 57.5     Day 20, PM, n=4 398.8 ± 36.3     Day 21, AM, n=2 400.0 ± 60.0     Day 21,PM, n=4 395.0 ± 38.6     Day 22, PM, n=4 397.5 ± 34.9     Day 23, AM, n=1 480.0 ± 99999     Day 23, PM, n=3 415.0 ± 39.0     Day 24, AM, n=1 460.0 ± 99999     Day 24, PM, n=3 423.3 ± 38.4     Day 25, AM, n=1 460.0 ± 99999     Day 25, PM, n=3 416.7 ± 33.8     Day 26, AM, n=1 450.0 ± 99999     Day 26, PM, n=3 418.3 ± 36.7     Day 27, AM, n=1 460.0 ± 99999     Day 27,PM, n=3 433.3 ± 49.7     Day 28, AM, n=1 460.0 ± 99999     Day 28, PM, n=3 430.0 ± 49.3     Day 29, PM, n=3 380.0 ± 75.5     Day 30, AM, n=1 460.0 ± 99999     Day 30, PM, n=3 388.3 ± 78.0     Day 31, AM, n=1 480.0 ± 99999     Day 31, PM, n=3 390.0 ± 85.0     Day 32, AM, n=1 500.0 ± 99999     Day 32, PM, n=3 370.0 ± 73.7     Day 33, AM, n=1 470.0 ± 99999     Day 33, PM, n=3 370.0 ± 70.9     Day 34, AM, n=1 460.0 ± 99999     Day 34, PM, n=3 390.0 ± 83.2     Day 35, AM, n=1 480.0 ± 99999     Day 35, PM, n=2 345.0 ± 105.0
Notes [53] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability of Placebo in Period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 25 mcg in Period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 25 mcg in Period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at the specified time points were analyzed.
End point type	Secondary
End point timeframe	Days 2,3,4,5,6,7 PM in period 1
End point values FF 25 mcg Number of subjects analysed 14 [54] Units: Liters per minute arithmetic mean (standard error)     Day 2, PM, n=14 479.6 ± 30.9     Day 3, PM, n=14 475.7 ± 32.9     Day 4, PM, n=14 473.0 ± 31.1     Day 5,PM, n=14 476.1 ± 26.6     Day 6, PM, n=13 503.1 ± 24.6     Day 7, PM, n=13 502.3 ± 28.1
Notes [54] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 25 mcg in Period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 25 mcg in Period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 25 mcg in Period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
End point type	Secondary
End point timeframe	Days 2,3,4,5,6,7 PM in period 2
End point values FF 25 mcg Number of subjects analysed 6 [55] Units: Liters per minute arithmetic mean (standard error)     Day 2, PM, n=5 572.0 ± 48.9     Day 3, PM, n=5 570.0 ± 54.5     Day 4, PM, n=5 568.0 ± 55.0     Day 5,PM, n=5 573.0 ± 54.9     Day 6, PM, n=6 550.8 ± 52.2     Day 7, PM, n=6 560.0 ± 45.3
Notes [55] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 25 mcg in Period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 100 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 100 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
End point type	Secondary
End point timeframe	Days 8,9,10,11,12,13,14 PM in period 1
End point values FF 100 mcg Number of subjects analysed 13 [56] Units: Liters per minute arithmetic mean (standard error)     Day 8, PM, n=13 497.3 ± 24.9     Day 9, PM, n=13 500.4 ± 28.2     Day 10, PM, n=13 491.2 ± 31.0     Day 11, PM, n=12 507.5 ± 30.9     Day 12, PM, n=13 500.2 ± 30.2     Day 13, PM, n=13 515.4 ± 29.7     Day 14, PM, n=13 505.8 ± 28.7
Notes [56] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 100 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 100 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 100 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise.
End point type	Secondary
End point timeframe	Days 8,9,10,11,12,13,14 PM in period 2
End point values FF 100 mcg Number of subjects analysed 6 [57] Units: Liters per minute arithmetic mean (standard error)     Day 8, PM 540.0 ± 43.8     Day 9, PM 567.5 ± 42.6     Day 10, PM 556.7 ± 43.4     Day 11, PM 561.7 ± 44.6     Day 12, PM 573.3 ± 50.0     Day 13, PM 563.3 ± 53.0     Day 14, PM 555.8 ± 46.9
Notes [57] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 100 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 200 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 200 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
End point type	Secondary
End point timeframe	Day 15,16,17,18,19,20,21 PM in period 1
End point values FF 200 mcg Number of subjects analysed 13 [58] Units: Liters per minute arithmetic mean (standard error)     Day 15,PM, n=13 500.8 ± 30.8     Day 16,PM, n=13 500.0 ± 28.7     Day 17,PM, n=13 506.2 ± 29.8     Day 18,PM, n=13 514.2 ± 31.6     Day 19,PM, n=13 505.4 ± 29.0     Day 20,PM, n=12 505.8 ± 30.8     Day 21,PM, n=12 485.0 ± 28.2
Notes [58] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 200 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 200 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 200 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles). 99999 indicates standard error could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Days 15,16,17,18,19,20 PM, Day 21 AM and PM in period 2
End point values FF 200 mcg Number of subjects analysed 6 [59] Units: Liters per minute arithmetic mean (standard error)     Day 15,PM, n=6 575.0 ± 52.9     Day 16,PM, n=6 575.0 ± 48.1     Day 17,PM, n=6 564.2 ± 46.6     Day 18,PM, n=6 573.3 ± 56.6     Day 19,PM, n=6 556.7 ± 53.4     Day 20,PM, n=6 571.7 ± 50.0     Day 21,AM, n=1 670.0 ± 99999     Day 21,PM, n=6 560.0 ± 38.3
Notes [59] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 200 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 400 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 400 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
End point type	Secondary
End point timeframe	Days 22,23,24,25,26,27,28 PM in period 1
End point values FF 400 mcg Number of subjects analysed 12 [60] Units: Liters per minute arithmetic mean (standard error)     Day 22 PM 496.7 ± 30.5     Day 23 PM 481.0 ± 25.6     Day 24 PM 484.6 ± 25.2     Day 25 PM 488.3 ± 26.2     Day 26 PM 496.7 ± 28.8     Day 27 PM 508.8 ± 28.9     Day 28 PM 486.7 ± 23.7
Notes [60] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 400 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 400 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 400 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at the indicated time points were analyzed (represented by n=X in the category titles).
End point type	Secondary
End point timeframe	Days 22,23,24,25,26,27,28 PM in period 2
End point values FF 400 mcg Number of subjects analysed 12 [61] Units: Liters per minute arithmetic mean (standard error)     Day 22 PM 556.7 ± 46.9     Day 23 PM 566.7 ± 47.8     Day 24 PM 571.7 ± 50.8     Day 25 PM 568.3 ± 52.7     Day 26 PM 565.0 ± 43.0     Day 27 PM 540.0 ± 43.3     Day 28 PM 541.7 ± 41.2
Notes [61] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 400 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 800 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 800 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise.
End point type	Secondary
End point timeframe	Days 29,30,31,32,33,34,35 PM in period 1
End point values FF 800 mcg Number of subjects analysed 12 [62] Units: Liters per minute arithmetic mean (standard error)     Day 29 PM 496.7 ± 27.0     Day 30 PM 487.1 ± 25.9     Day 31 PM 488.3 ± 24.1     Day 32 PM 481.3 ± 25.8     Day 33 PM 481.5 ± 24.9     Day 34 PM 487.5 ± 28.7     Day 35 PM 471.0 ± 26.6
Notes [62] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 800 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FF 800 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FF 800 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise.
End point type	Secondary
End point timeframe	Days 29,30,31,32,33,34,35 PM in period 2
End point values FF 400 mcg Number of subjects analysed 6 [63] Units: Liters per minute arithmetic mean (standard error)     Day 29 PM 576.7 ± 44.9     Day 30 PM 560.0 ± 48.7     Day 31 PM 553.3 ± 45.0     Day 32 PM 565.0 ± 50.7     Day 33 PM 580.0 ± 48.9     Day 34 PM 568.3 ± 42.3     Day 35 PM 556.7 ± 44.9
Notes [63] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FF 800 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 50 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 50 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
End point type	Secondary
End point timeframe	Days 2,3,4,5,6,7 PM in period 1
End point values FP 50 mcg Number of subjects analysed 15 [64] Units: Liters per minute arithmetic mean (standard error)     Day 2 PM, n=15 529.3 ± 28.0     Day 3 PM, n=14 533.6 ± 30.3     Day 4 PM, n=15 532.3 ± 30.8     Day 5 PM, n=15 524.0 ± 29.9     Day 6 PM, n=14 519.3 ± 26.4     Day 7 PM, n=14 502.9 ± 35.1
Notes [64] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 50 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 50 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 50 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed (represented by n=X in the category titles). 99999 indicates standard error could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Day 2,3,4,5,6,7 AM and PM in period 2
End point values FP 50 mcg Number of subjects analysed 6 [65] Units: Liters per minute arithmetic mean (standard error)     Day 2 AM, n=1 600.0 ± 99999     Day 2 PM, n=6 490.0 ± 40.6     Day 3 AM, n=1 600.0 ± 99999     Day 3 PM, n=6 486.7 ± 42.3     Day 4 AM, n=1 590.0 ± 99999     Day 4 PM, n=6 491.7 ± 42.6     Day 5 AM, n=1 600.0 ± 99999     Day 5 PM, n=6 491.7 ± 44.6     Day 6 AM, n=1 600.0 ± 99999     Day 6 PM, n=6 490.0 ± 44.3     Day 7 AM, n=1 600.0 ± 99999     Day 7 PM, n=6 466.0 ± 48.9
Notes [65] - All subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 50 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 200 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 200 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed (represented by n=X in the category titles). 99999 indicates standard error could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Days 8,9,1,0,11,12,13,14 AM and PM in period 1
End point values FP 200 mcg Number of subjects analysed 14 [66] Units: Liters per minute arithmetic mean (standard error)     Day 8 AM, n=1 540.0 ± 99999     Day 8 PM, n=13 532.7 ± 33.2     Day 9 AM, n=11 500.9 ± 38.3     Day 9 PM, n=14 517.9 ± 26.8     Day 10 AM, n=10 521.0 ± 39.0     Day 10 PM, n=14 513.2 ± 28.5     Day 11 AM, n=11 476.4 ± 35.4     Day 11 PM, n=14 512.1 ± 30.0     Day 12 AM, n=11 506.8 ± 38.0     Day 12 PM, n=13 528.8 ± 34.3     Day 13 AM, n=11 500.0 ± 38.2     Day 13 PM, n=14 514.6 ± 31.1     Day 14 AM, n=13 496.2 ± 31.7     Day14 PM, n=13 522.7 ± 32.9
Notes [66] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 200 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 200 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 200 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed. 99999 indicates standard error could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Day 8,9,1,0,11,12,13,14 AM and PM in period 2
End point values FP 200 mcg Number of subjects analysed 6 [67] Units: Liters per minute arithmetic mean (standard error)     Day 8 AM, n=1 610.0 ± 99999     Day 8 PM, n=6 500.0 ± 43.2     Day 9 AM, n=5 506.0 ± 39.5     Day 9 PM, n=6 488.3 ± 43.7     Day 10 AM, n=4 515.0 ± 44.0     Day 10 PM, n=6 490.0 ± 47.1     Day 11 AM, n=5 504.0 ± 36.1     Day 11 PM, n=6 485.0 ± 42.6     Day 12 AM, n=5 508.0 ± 41.4     Day 12 PM, n=6 493.3 ± 42.8     Day 13 AM, n=5 500.0 ± 40.1     Day 13 PM, n=6 495.0 ± 45.8     Day 14 AM, n=5 438.0 ± 46.6     Day 14 PM, n=6 495.8 ± 48.8
Notes [67] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 200 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 500 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 500 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed. 99999 indicates standard error could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Day 15 PM, Day 16,17,18,19,20,21,22,23,24,25,26,27,28 AM and PM in period 1
End point values FP 500 mcg Number of subjects analysed 14 [68] Units: Liters per minute arithmetic mean (standard error)     Day 15 PM, n=14 527.5 ± 29.7     Day 16 AM, n=13 503.8 ± 31.9     Day 16 PM, n=14 520.4 ± 29.5     Day 17 AM, n=13 510.0 ± 30.3     Day 17 PM, n=14 508.6 ± 31.2     Day 18 AM, n=12 497.5 ± 34.7     Day 18 PM, n=13 505.8 ± 28.5     Day 19 AM, n=12 505.8 ± 35.2     Day 19 PM, n=13 506.9 ± 29.5     Day 20 AM, n=11 518.2 ± 35.9     Day 20 PM, n=13 517.3 ± 30.4     Day 21 AM, n=13 501.9 ± 32.1     Day 21 PM, n=11 493.6 ± 30.0     Day 22 AM, n=1 520.0 ± 99999     Day 22 PM, n=1 540.0 ± 99999     Day 23 AM, n=1 530.0 ± 99999     Day 23 PM, n=1 550.0 ± 99999     Day 24 AM, n=1 530.0 ± 99999     Day 24 PM, n=1 540.0 ± 99999     Day 25 AM, n=1 510.0 ± 99999     Day 25 PM, n=1 500.0 ± 99999     Day 26 AM, n=1 520.0 ± 99999     Day 26 PM, n=1 550.0 ± 99999     Day 27 AM, n=1 530.0 ± 99999     Day 27 PM, n=1 580.0 ± 99999     Day 28 AM, n=1 530.0 ± 99999     Day 28 PM, n=1 500.0 ± 99999
Notes [68] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 500 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 500 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 500 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 15 PM, Days 16,17,18,19,20,21 AM and PM in period 2
End point values FP 500 mcg Number of subjects analysed 6 [69] Units: Liters per minute arithmetic mean (standard error)     Day 15 PM, n=6 486.7 ± 43.8     Day 16 AM, n=6 476.7 ± 43.8     Day 16 PM, n=6 503.3 ± 46.8     Day 17 AM, n=6 493.3 ± 44.0     Day 17 PM, n=6 500.0 ± 45.9     Day 18 AM, n=6 476.7 ± 39.9     Day 18 PM, n=6 495.0 ± 42.8     Day 19 AM, n=5 454.0 ± 44.3     Day 19 PM, n=6 500.0 ± 45.1     Day 20 AM, n=5 524.0 ± 43.6     Day 20 PM, n=6 501.7 ± 50.6     Day 21 AM, n=6 490.0 ± 44.2     Day 21 PM, n=6 496.7 ± 48.4
Notes [69] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 500 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 1000 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 1000 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed. 99999 indicates standard error could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Day 22 PM, Days 23,24,25,26,27,28,29,30,31,32,33,34,35 AM and PM in period 1
End point values FP 1000 mcg Number of subjects analysed 11 [70] Units: Liters per minute arithmetic mean (standard error)     Day 22 PM, n=6 523.2 ± 30.5     Day 23 AM, n=11 511.8 ± 36.4     Day 23 PM, n=11 516.4 ± 38.4     Day 24 AM, n=11 521.8 ± 38.0     Day 24 PM, n=11 520.9 ± 37.1     Day 25 AM, n=11 489.5 ± 35.1     Day 25 PM, n=10 521.0 ± 42.7     Day 26 AM, n=11 502.7 ± 37.0     Day 26 PM, n=11 517.3 ± 35.7     Day 27 AM, n=11 493.6 ± 33.0     Day 27 PM, n=11 523.6 ± 37.7     Day 28 AM, n=11 500.0 ± 40.6     Day 28,PM, n=11 516.4 ± 33.9     Day 29 PM, n=1 530.0 ± 99999     Day 30 AM, n=1 520.0 ± 99999     Day 30 PM, n=1 530.0 ± 99999     Day 31 AM, n=1 510.0 ± 99999     Day 31 PM, n=1 530.0 ± 99999     Day 32 AM, n=1 520.0 ± 99999     Day 32 PM, n=1 550.0 ± 99999     Day 33 AM, n=1 530.0 ± 99999     Day 33 PM, n=1 540.0 ± 99999     Day 34 AM, n=1 510.0 ± 99999     Day 34 PM, n=1 520.0 ± 99999     Day 35 AM, n=1 540.0 ± 99999     Day 35 PM, n=1 550.0 ± 99999
Notes [70] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 1000 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 1000 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 1000 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 22 PM, Days 23,24,25,26,27,28 AM and PM in period 2
End point values FP 1000 mcg Number of subjects analysed 6 [71] Units: Liters per minute arithmetic mean (standard error)     Day 22 PM, n=6 493.3 ± 42.8     Day 23 AM, n=6 480.0 ± 43.4     Day 23 PM, n=6 506.7 ± 43.5     Day 24 AM, n=6 481.7 ± 39.4     Day 24 PM, n=6 505.0 ± 45.3     Day 25 AM, n=6 491.7 ± 43.9     Day 25 PM, n=6 510.0 ± 51.7     Day 26 AM, n=6 485.0 ± 45.3     Day 26 PM, n=6 501.7 ± 49.9     Day 27 AM, n=6 475.0 ± 42.3     Day 27 PM, n=6 490.0 ± 43.2     Day 28 AM, n=5 452.0 ± 47.7     Day 28,PM, n=5 476.0 ± 56.8
Notes [71] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 1000 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 2000 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 2000 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 29 PM, Days 30,31,32,33,34,35 AM and PM in period 1
End point values FP 2000 mcg Number of subjects analysed 10 [72] Units: Liters per minute arithmetic mean (standard error)     Day 29 PM, n=10 520.5 ± 36.5     Day 30 AM, n=10 505.0 ± 39.0     Day 30 PM, n=10 520.0 ± 40.9     Day 31 AM, n=10 507.0 ± 37.0     Day 31 PM, n=10 521.0 ± 41.7     Day 32 AM, n=10 500.0 ± 39.6     Day 32 PM, n=10 524.0 ± 41.9     Day 33 AM, n=10 511.0 ± 40.7     Day 33 PM, n=10 511.5 ± 43.2     Day 34 AM, n=10 519.0 ± 38.9     Day 34 PM, n=10 517.0 ± 38.9     Day 35 AM, n=9 514.4 ± 40.4     Day 35 PM, n=9 543.9 ± 44.1
Notes [72] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 2000 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for FP 2000 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for FP 2000 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 29 PM, Days 30,31,32,33,34,35 AM and PM in period 2
End point values FP 2000 mcg Number of subjects analysed 6 [73] Units: Liters per minute arithmetic mean (standard error)     Day 29 PM 506.7 ± 45.8     Day 30 AM 493.3 ± 45.0     Day 30 PM 496.7 ± 46.8     Day 31 AM 486.7 ± 48.0     Day 31 PM 485.0 ± 41.6     Day 32 AM 488.3 ± 44.7     Day 32 PM 513.3 ± 52.6     Day 33 AM 495.0 ± 45.3     Day 33 PM 498.3 ± 44.1     Day 34 AM 481.7 ± 46.0     Day 34 PM 498.3 ± 47.7     Day 35 AM 483.3 ± 44.2     Day 35 PM 493.3 ± 46.3
Notes [73] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for FP 2000 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 100 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 100 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed. 99999 indicates standard error could not be calculated as only one participant was analyzed.
End point type	Secondary
End point timeframe	Days 2 to 6 AM and PM, Day 7 PM in period 1
End point values BUD 100 mcg Number of subjects analysed 12 [74] Units: Liters per minute arithmetic mean (standard error)     Day 2 AM, n=1 600.0 ± 99999     Day 2 PM, n=12 512.9 ± 33.4     Day 3 AM, n=1 600.0 ± 99999     Day 3 PM, n=12 517.1 ± 31.2     Day 4 AM, n=1 625.0 ± 99999     Day 4 PM, n=12 524.2 ± 32.9     Day 5 AM, n=1 600.0 ± 99999     Day 5 PM, n=12 520.8 ± 32.3     Day 6 AM, n=1 600.0 ± 99999     Day 6 PM, n=12 523.3 ± 33.5     Day 7 PM, n=12 527.5 ± 33.4
Notes [74] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 100 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 100 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 100 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 2,3,4,5,6,7 PM in period 2
End point values BUD 100 mcg Number of subjects analysed 4 [75] Units: Liters per minute arithmetic mean (standard error)     Day 2 PM, n=4 557.5 ± 28.3     Day 3 PM, n=4 547.5 ± 60.1     Day 4 PM, n=4 545.0 ± 27.2     Day 5 PM, n=4 552.5 ± 46.0     Day 6 PM, n=4 577.5 ± 26.5     Day 7 PM, n=3 603.3 ± 32.8
Notes [75] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 100 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 400 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 400 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Days 8 PM, Day 9 to 14 AM and PM in period 1
End point values BUD 400 mcg Number of subjects analysed 12 [76] Units: Liters per minute arithmetic mean (standard error)     Day 8 PM, n=12 521.7 ± 31.5     Day 9 AM, n=10 473.0 ± 30.5     Day 9 PM, n=12 515.4 ± 34.3     Day 10 AM, n=10 470.0 ± 33.9     Day 10 PM, n=12 512.9 ± 32.8     Day 11 AM, n=10 466.7 ± 36.0     Day 11 PM, n=11 492.5 ± 35.2     Day 12 AM, n=9 451.1 ± 28.6     Day 12 PM, n=11 509.5 ± 33.7     Day 13 AM, n=9 457.8 ± 33.9     Day 13 PM, n=11 506.8 ± 33.1     Day 14 AM, n=11 480.5 ± 30.3     Day 14 PM, n=11 496.4 ± 32.1
Notes [76] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 400 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 400 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 400 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 8 PM, Days 9 to 14 AM and PM in period 2
End point values BUD 400 mcg Number of subjects analysed 5 [77] Units: Liters per minute arithmetic mean (standard error)     Day 8 PM 560.0 ± 43.3     Day 9 AM 552.0 ± 40.1     Day 9 PM 560.0 ± 34.7     Day 10 AM 552.0 ± 34.9     Day 10 PM 556.0 ± 30.7     Day 11 AM 562.0 ± 26.7     Day 11 PM 574.0 ± 30.4     Day 12 AM 568.0 ± 29.3     Day 12 PM 578.0 ± 44.2     Day 13 AM 562.0 ± 28.1     Day 13 PM 588.0 ± 37.6     Day 14 AM 586.0 ± 22.2     Day 14 PM 590.0 ± 44.6
Notes [77] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 400 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 800 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 800 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Days 15,16, 17, 18, 19, 20, 21 AM and PM in period 1
End point values BUD 800 mcg Number of subjects analysed 11 [78] Units: Liters per minute arithmetic mean (standard error)     Day 15 AM, n=1 610.0 ± 99999     Day 15 PM, n=11 515.5 ± 30.1     Day 16 AM, n=11 494.5 ± 31.9     Day 16 PM, n=11 507.3 ± 34.9     Day 17 AM, n=11 484.1 ± 33.4     Day 17 PM, n=11 505.0 ± 34.8     Day 18 AM, n=11 492.7 ± 33.4     Day 18 PM, n=11 503.2 ± 36.4     Day 19 AM, n=11 483.2 ± 29.7     Day 19 PM, n=11 487.7 ± 38.0     Day 20 AM, n=11 483.6 ± 31.7     Day 20 PM, n=11 517.7 ± 33.9     Day 21 AM, n=11 490.5 ± 27.2     Day 21 PM, n=11 509.1 ± 32.9
Notes [78] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 800 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 800 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 800 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 15 PM, Day 16, 17, 18, 19, 20, 21 AM and PM in period 2
End point values BUD 800 mcg Number of subjects analysed 5 [79] Units: Liters per minute arithmetic mean (standard error)     Day 15 PM 578.0 ± 32.0     Day 16 AM 568.0 ± 37.6     Day 16 PM 572.0 ± 45.3     Day 17 AM 572.0 ± 27.8     Day 17 PM 558.0 ± 46.0     Day 18 AM 558.0 ± 45.8     Day 18 PM 568.0 ± 53.1     Day 19 AM 572.0 ± 46.4     Day 19 PM 584.0 ± 47.3     Day 20 AM 590.0 ± 37.6     Day 20 PM 590.0 ± 37.6     Day 21 AM 574.0 ± 23.5     Day 21 PM 606.0 ± 38.0
Notes [79] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 800 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 1600 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 1600 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 22 PM, Day 23,24,25,26,27,28 AM and PM in period 1
End point values BUD 1600 mcg Number of subjects analysed 11 [80] Units: Liters per minute arithmetic mean (standard error)     Day 22 PM 506.4 ± 33.9     Day 23 AM 496.4 ± 29.8     Day 23 PM 512.7 ± 32.3     Day 24 AM 498.2 ± 34.8     Day 24 PM 510.5 ± 34.9     Day 25 AM 500.5 ± 32.8     Day 25 PM 514.1 ± 33.2     Day 26 AM 499.1 ± 31.3     Day 26 PM 512.3 ± 35.2     Day 27 AM 491.4 ± 31.0     Day 27 PM 497.7 ± 37.3     Day 28 AM 476.8 ± 27.9     Day 28 PM 526.8 ± 33.9
Notes [80] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 1600 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 1600 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 1600 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 22 PM, Days 23,24,25,26,27,28 AM and PM in period 2
End point values BUD 1600 mcg Number of subjects analysed 5 [81] Units: Liters per minute arithmetic mean (standard error)     Day 22 PM, n=5 594.0 ± 47.8     Day 23 AM, n=5 578.0 ± 40.0     Day 23 PM, n=5 586.0 ± 46.4     Day 24 AM, n=5 556.0 ± 37.8     Day 24 PM, n=5 556.0 ± 45.2     Day 25 AM, n=5 564.0 ± 50.6     Day 25 PM, n=5 594.0 ± 45.4     Day 26 AM, n=5 584.0 ± 45.6     Day 26 PM, n=5 568.0 ± 51.1     Day 27 AM, n=5 568.0 ± 52.1     Day 27 PM, n=5 584.0 ± 35.3     Day 28 AM, n=5 574.0 ± 30.1     Day 28 PM, n=4 630.0 ± 46.0
Notes [81] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 1600 mcg in period 2 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 3200 mcg in period 1 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 3200 mcg in period 1
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed (represented by n=X in the category titles).
End point type	Secondary
End point timeframe	Day 29 PM, Day 30, 31,32,33,34,35 AM and PM in period 1
End point values BUD 3200 mcg Number of subjects analysed 10 [82] Units: Liters per minute arithmetic mean (standard error)     Day 29 PM, n=10 493.0 ± 31.9     Day 30 AM, n=10 482.0 ± 33.5     Day 30 PM, n=10 502.0 ± 33.3     Day 31 AM, n=10 482.0 ± 34.0     Day 31 PM, n=10 496.0 ± 32.4     Day 32 AM, n=10 482.0 ± 30.1     Day 32 PM, n=10 488.0 ± 33.0     Day 33 AM, n=10 483.0 ± 29.1     Day 33 PM, n=10 490.0 ± 35.0     Day 34 AM, n=10 489.0 ± 31.3     Day 34 PM, n=9 522.2 ± 33.4     Day 35 AM, n=10 474.0 ± 33.8     Day 35 PM, n=10 488.0 ± 30.6
Notes [82] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 3200 mcg in period 1 Top of page

Secondary: PEFR as a measure of safety and tolerability for BUD 3200 mcg in period 2 Top of page
End point title	PEFR as a measure of safety and tolerability for BUD 3200 mcg in period 2
End point description	PEFR is a participant's maximum speed of expiration and was measured using a peak flow meter. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed (represented by n=X in the category titles).
End point type	Secondary
End point timeframe	Day 29 PM, Day 30, 31,32,33,34,35 AM and PM in period 2
End point values BUD 3200 mcg Number of subjects analysed 5 [83] Units: Liters per minute arithmetic mean (standard error)     Day 29 PM, n=5 596.0 ± 43.8     Day 30 AM, n=5 604.0 ± 22.7     Day 30 PM, n=5 586.0 ± 41.5     Day 31 AM, n=4 562.5 ± 33.5     Day 31 PM, n=4 547.5 ± 43.8     Day 32 AM, n=4 592.5 ± 38.6     Day 32 PM, n=4 587.5 ± 18.8     Day 33 AM, n=4 567.5 ± 30.3     Day 33 PM, n=4 565.0 ± 42.9     Day 34 AM, n=4 585.0 ± 38.4     Day 34 PM, n=4 583.8 ± 29.6     Day 35 AM, n=4 577.5 ± 35.6     Day 35 PM, n=4 597.5 ± 38.6
Notes [83] - All Subjects Population.
No statistical analyses for this end point

Secondary: PEFR as a measure of safety and tolerability for BUD 3200 mcg in period 2 Top of page

Secondary: Number of participants with clinically significant abnormal vital signs: Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) Top of page
End point title	Number of participants with clinically significant abnormal vital signs: Systolic blood pressure (SBP) and Diastolic blood pressure (DBP)
End point description	SBP and DBP were measured after participants had rested in supine position for at least 5 minutes. Results are presented treatment wise. No data collected separately for this outcome measure as any abnormal value would be recorded as an Adverse Event.
End point type	Secondary
End point timeframe	Up to Week 18
End point values FF 100 mcg FP 200 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg FF 800 mcg Placebo FF 25 mcg FF 200 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 3200 mcg FF 400 mcg Number of subjects analysed 0 [84] 0 [85] 0 [86] 0 [87] 0 [88] 0 [89] 0 [90] 0 [91] 0 [92] 0 [93] 0 [94] 0 [95] 0 [96] 0 [97] 0 [98] 0 [99] Units: Participants
Notes [84] - All Subjects Population. [85] - All Subjects Population. [86] - All Subjects Population. [87] - All Subjects Population. [88] - All Subjects Population. [89] - All Subjects Population. [90] - All Subjects Population. [91] - All Subjects Population. [92] - All Subjects Population. [93] - All Subjects Population. [94] - All Subjects Population. [95] - All Subjects Population. [96] - All Subjects Population. [97] - All Subjects Population. [98] - All Subjects Population. [99] - All Subjects Population.
No statistical analyses for this end point

Secondary: Number of participants with clinically significant abnormal vital signs: Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) Top of page

Secondary: Number of participants with clinically significant abnormal vital signs: Pulse rate Top of page
End point title	Number of participants with clinically significant abnormal vital signs: Pulse rate
End point description	Pulse rate was measured after participants had rested in supine position for at least 5 minutes. Results are presented treatment wise. No data collected separately for this outcome measure as any abnormal value would be recorded as an Adverse Event.
End point type	Secondary
End point timeframe	Up to Week 18
End point values FF 100 mcg FP 200 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg FF 800 mcg Placebo FF 25 mcg FF 200 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 3200 mcg FF 400 mcg Number of subjects analysed 0 [100] 0 [101] 0 [102] 0 [103] 0 [104] 0 [105] 0 [106] 0 [107] 0 [108] 0 [109] 0 [110] 0 [111] 0 [112] 0 [113] 0 [114] 0 [115] Units: Participants
Notes [100] - All Subjects Population. [101] - All Subjects Population. [102] - All Subjects Population. [103] - All Subjects Population. [104] - All Subjects Population. [105] - All Subjects Population. [106] - All Subjects Population. [107] - All Subjects Population. [108] - All Subjects Population. [109] - All Subjects Population. [110] - All Subjects Population. [111] - All Subjects Population. [112] - All Subjects Population. [113] - All Subjects Population. [114] - All Subjects Population. [115] - All Subjects Population.
No statistical analyses for this end point

Secondary: Number of participants with clinically significant abnormal vital signs: Pulse rate Top of page

Secondary: Number of participants with clinically significant abnormal vital signs: Respiratory rate Top of page
End point title	Number of participants with clinically significant abnormal vital signs: Respiratory rate
End point description	Respiratory rate was measured after participants had rested in supine position for at least 5 minutes. Results are presented treatment wise. No data collected separately for this outcome measure as any abnormal value would be recorded as an Adverse Event.
End point type	Secondary
End point timeframe	Up to Week 18
End point values FF 100 mcg FP 200 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg FF 800 mcg Placebo FF 25 mcg FF 200 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 3200 mcg FF 400 mcg Number of subjects analysed 0 [116] 0 [117] 0 [118] 0 [119] 0 [120] 0 [121] 0 [122] 0 [123] 0 [124] 0 [125] 0 [126] 0 [127] 0 [128] 0 [129] 0 [130] 0 [131] Units: Participants
Notes [116] - All Subjects Population. [117] - All Subjects Population. [118] - All Subjects Population. [119] - All Subjects Population. [120] - All Subjects Population. [121] - All Subjects Population. [122] - All Subjects Population. [123] - All Subjects Population. [124] - All Subjects Population. [125] - All Subjects Population. [126] - All Subjects Population. [127] - All Subjects Population. [128] - All Subjects Population. [129] - All Subjects Population. [130] - All Subjects Population. [131] - All Subjects Population.
No statistical analyses for this end point

Secondary: Number of participants with clinically significant abnormal vital signs: Respiratory rate Top of page

Secondary: Number of Participants with clinically significant abnormal vital signs: Temperature Top of page
End point title	Number of Participants with clinically significant abnormal vital signs: Temperature
End point description	Temperature was measured after participants have been rested in supine position for at least 5 minutes. Results are presented treatment wise. No data collected separately for this outcome measure as any abnormal value would be recorded as an Adverse Event.
End point type	Secondary
End point timeframe	Up to Week 18
End point values FF 100 mcg FF 400 mcg FP 200 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg FF 800 mcg Placebo FF 25 mcg FF 200 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 3200 mcg Number of subjects analysed 0 [132] 0 [133] 0 [134] 0 [135] 0 [136] 0 [137] 0 [138] 0 [139] 0 [140] 0 [141] 0 [142] 0 [143] 0 [144] 0 [145] 0 [146] 0 [147] Units: Participants
Notes [132] - All Subjects Population. [133] - All Subjects Population. [134] - All Subjects Population. [135] - All Subjects Population. [136] - All Subjects Population. [137] - All Subjects Population. [138] - All Subjects Population. [139] - All Subjects Population. [140] - All Subjects Population. [141] - All Subjects Population. [142] - All Subjects Population. [143] - All Subjects Population. [144] - All Subjects Population. [145] - All Subjects Population. [146] - All Subjects Population. [147] - All Subjects Population.
No statistical analyses for this end point

Secondary: Number of Participants with clinically significant abnormal vital signs: Temperature Top of page

Secondary: Number of participants with abnormal physical examination Top of page
End point title	Number of participants with abnormal physical examination
End point description	Physical examinations included assessment of the cardiovascular, respiratory, gastrointestinal, skin, abdomen (liver and spleen), and neurological systems. This analysis was planned and data was not collected and captured in the database. Results are presented treatment wise.
End point type	Secondary
End point timeframe	Up to Week 18
End point values Placebo FF 25 mcg FF 100 mcg FF 200 mcg FF 400 mcg FF 800 mcg FP 50 mcg FP 200 mcg FP 500 mcg FP 1000 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg BUD 3200 mcg Number of subjects analysed 0 [148] 0 [149] 0 [150] 0 [151] 0 [152] 0 [153] 0 [154] 0 [155] 0 [156] 0 [157] 0 [158] 0 [159] 0 [160] 0 [161] 0 [162] 0 [163] Units: Participants
Notes [148] - All Subjects Population. [149] - All Subjects Population. [150] - All Subjects Population. [151] - All Subjects Population. [152] - All Subjects Population. [153] - All Subjects Population. [154] - All Subjects Population. [155] - All Subjects Population. [156] - All Subjects Population. [157] - All Subjects Population. [158] - All Subjects Population. [159] - All Subjects Population. [160] - All Subjects Population. [161] - All Subjects Population. [162] - All Subjects Population. [163] - All Subjects Population.
No statistical analyses for this end point

Secondary: Number of participants with abnormal physical examination Top of page

Secondary: Number of participants with clinically significant abnormal hematology parameters Top of page
End point title	Number of participants with clinically significant abnormal hematology parameters
End point description	Blood samples were collected for assessement of following hematology parameters: basophils, eosinophils, Erythrocyte mean corpuscular volume (MCV), hemoglobin, hematocrit, Erythrocyte mean corpuscular hemoglobin (MCH), leukocytes, lymphocytes, monocytes, platelets. Results are presented treatment wise. Only participants with clinically significant abnormal hematology data was reported.
End point type	Secondary
End point timeframe	Up to Week 18
End point values FF 100 mcg FF 400 mcg FP 200 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg FF 800 mcg Placebo FF 25 mcg FF 200 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 3200 mcg Number of subjects analysed 19 [164] 18 [165] 20 [166] 17 [167] 18 [168] 18 [169] 18 [170] 18 [171] 18 [172] 17 [173] 20 [174] 19 [175] 21 [176] 20 [177] 18 [178] 18 [179] Units: Participants 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Notes [164] - All Subjects Population. [165] - All Subjects Population. [166] - All Subjects Population. [167] - All Subjects Population. [168] - All Subjects Population. [169] - All Subjects Population. [170] - All Subjects Population. [171] - All Subjects Population. [172] - All Subjects Population. [173] - All Subjects Population. [174] - All Subjects Population. [175] - All Subjects Population. [176] - All Subjects Population. [177] - All Subjects Population. [178] - All Subjects Population. [179] - All Subjects Population.
No statistical analyses for this end point

Secondary: Number of participants with clinically significant abnormal hematology parameters Top of page

Secondary: Number of participants with clinically significant abnormal chemistry parameters Top of page
End point title	Number of participants with clinically significant abnormal chemistry parameters
End point description	Blood samples were collecte for assessment of following chemistry parametres:Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, alkaline phosphatase, bilirubin, calcium, creatinine, glucose, direct bilirubin, potassium, protein, sodium, urea. Results are presented treatment wise. Only participants with clinically significant abnormal chemistry data was reported.
End point type	Secondary
End point timeframe	Up to Week 18
End point values FF 100 mcg FF 400 mcg FP 200 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg FF 800 mcg Placebo FF 25 mcg FF 200 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 3200 mcg Number of subjects analysed 19 [180] 18 [181] 20 [182] 17 [183] 18 [184] 18 [185] 18 [186] 18 [187] 18 [188] 17 [189] 20 [190] 19 [191] 21 [192] 20 [193] 18 [194] 18 [195] Units: Participants 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Notes [180] - All Subjects Population. [181] - All Subjects Population. [182] - All Subjects Population. [183] - All Subjects Population. [184] - All Subjects Population. [185] - All Subjects Population. [186] - All Subjects Population. [187] - All Subjects Population. [188] - All Subjects Population. [189] - All Subjects Population. [190] - All Subjects Population. [191] - All Subjects Population. [192] - All Subjects Population. [193] - All Subjects Population. [194] - All Subjects Population. [195] - All Subjects Population.
No statistical analyses for this end point

Secondary: Number of participants with clinically significant abnormal chemistry parameters Top of page

Secondary: Number of participants with clinically significant abnormal urinalysis parameters Top of page
End point title	Number of participants with clinically significant abnormal urinalysis parameters
End point description	Urine sample were collected to assess following urine parameters: potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick. Results are presented treatment wise. Only participants with clinically significant abnormal urinalysis data was reported.
End point type	Secondary
End point timeframe	Up to Week 18
End point values FF 100 mcg FF 400 mcg FP 200 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg FF 800 mcg Placebo FF 25 mcg FF 200 mcg FP 50 mcg FP 500 mcg FP 1000 mcg BUD 3200 mcg Number of subjects analysed 19 [196] 18 [197] 20 [198] 17 [199] 18 [200] 18 [201] 18 [202] 18 [203] 18 [204] 17 [205] 20 [206] 19 [207] 21 [208] 20 [209] 18 [210] 18 [211] Units: Participants 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Notes [196] - All Subjects Population. [197] - All Subjects Population. [198] - All Subjects Population. [199] - All Subjects Population. [200] - All Subjects Population. [201] - All Subjects Population. [202] - All Subjects Population. [203] - All Subjects Population. [204] - All Subjects Population. [205] - All Subjects Population. [206] - All Subjects Population. [207] - All Subjects Population. [208] - All Subjects Population. [209] - All Subjects Population. [210] - All Subjects Population. [211] - All Subjects Population.
No statistical analyses for this end point

Secondary: Number of participants with clinically significant abnormal urinalysis parameters Top of page

Secondary: Forced Expiratory Volume in 1 Second (FEV 1) in Period 1 Top of page
End point title	Forced Expiratory Volume in 1 Second (FEV 1) in Period 1
End point description	FEV1 was measured with participants in a sitting position using a calibrated spirometer in accordance with American Thoracic Society (ATS) guidelines using European Respiratory Society (ERS) guidelines for predicted values. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 1 (pre-dose) in Period 1
End point values Placebo Fluticasone furoate (FF) Fluticasone Furoate (FF) Budesonide (BUD) Number of subjects analysed 12 [212] 14 [213] 15 [214] 12 [215] Units: Liter     arithmetic mean (standard error) 3.18 ± 0.151 3.02 ± 0.166 3.50 ± 0.269 3.29 ± 0.274
Notes [212] - All Subjects Population. [213] - All Subjects Population. [214] - All Subjects Population. [215] - All Subjects Population.
No statistical analyses for this end point

Secondary: Forced Expiratory Volume in 1 Second (FEV 1) in Period 1 Top of page

Secondary: Forced Expiratory Volume in 1 Second (FEV 1) in Period 2 Top of page
End point title	Forced Expiratory Volume in 1 Second (FEV 1) in Period 2
End point description	FEV1 was measured with participants in a sitting position using a calibrated spirometer in accordance with American Thoracic Society (ATS) guidelines using European Respiratory Society (ERS) guidelines for predicted values. Results are presented treatment wise. Only those participants with data available at specified time point were analyzed.
End point type	Secondary
End point timeframe	Day 1 (pre-dose) in Period 2
End point values Placebo Fluticasone furoate (FF) Fluticasone Propionate (FP) Budesonide (BUD) Number of subjects analysed 5 [216] 6 [217] 6 [218] 6 [219] Units: Liter     arithmetic mean (standard error) 2.67 ± 0.482 3.44 ± 0.431 2.68 ± 0.278 3.46 ± 0.257
Notes [216] - All Subjects Population. [217] - All Subjects Population. [218] - All Subjects Population. [219] - All Subjects Population.
No statistical analyses for this end point

Secondary: Forced Expiratory Volume in 1 Second (FEV 1) in Period 2 Top of page

Secondary: Forced Vital Capacity (FVC) in Period 1 Top of page
End point title	Forced Vital Capacity (FVC) in Period 1
End point description	FVC was measured with participants in a sitting position using a calibrated spirometer in accordance with ATS guidelines using ERS guidelines for predicted values. Results are presented treatment wise.
End point type	Secondary
End point timeframe	Day 1 (pre-dose) in Period 1
End point values Placebo Fluticasone furoate (FF) Fluticasone Furoate (FF) Budesonide (BUD) Number of subjects analysed 12 [220] 14 [221] 15 [222] 12 [223] Units: Liter     arithmetic mean (standard error) 4.55 ± 0.221 4.36 ± 0.222 5.15 ± 0.287 4.70 ± 0.406
Notes [220] - All Subjects Population. [221] - All Subjects Population. [222] - All Subjects Population. [223] - All Subjects Population.
No statistical analyses for this end point

Secondary: Forced Vital Capacity (FVC) in Period 1 Top of page

Secondary: Forced Vital Capacity (FVC) in Period 2 Top of page
End point title	Forced Vital Capacity (FVC) in Period 2
End point description	FVC was measured with participants in a sitting position using a calibrated spirometer in accordance with ATS guidelines using ERS guidelines for predicted values. Results are presented treatment wise.
End point type	Secondary
End point timeframe	Day 1 (pre-dose) in Period 2
End point values Placebo Fluticasone furoate (FF) Fluticasone Propionate (FP) Budesonide (BUD) Number of subjects analysed 5 [224] 6 [225] 6 [226] 6 [227] Units: Liter     arithmetic mean (standard error) 4.11 ± 0.570 4.85 ± 0.602 4.09 ± 0.386 4.90 ± 0.410
Notes [224] - All Subjects Population. [225] - All Subjects Population. [226] - All Subjects Population. [227] - All Subjects Population.
No statistical analyses for this end point

Secondary: Forced Vital Capacity (FVC) in Period 2 Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Serious adverse events and non-serious adverse events were collected up to 18 weeks.
Adverse event reporting additional description	All subjects Population was used to collect the adverse events.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	21.1
Reporting groups
Reporting group title	Placebo
Reporting group description	Participants received matching placebo ELLIPTA or DISKUS as total daily dose for 7 days.
Reporting group title	FF 25 mcg
Reporting group description	Participants received placebo FF ELLIPTA 25 mcg 1 puff as total daily dose for 7 days.
Reporting group title	FF 100 mcg
Reporting group description	Participants received FF ELLIPTA 100 mcg 1 puff PM as total daily dose for 7 days.
Reporting group title	FF 200 mcg
Reporting group description	Participants received FF ELLIPTA 200 mcg 1 puff PM as total daily dose for 7 days.
Reporting group title	FF 400 mcg
Reporting group description	Participants received FF ELLIPTA 200 mcg 2 puffs PM as total daily dose for 7 days.
Reporting group title	FF 800 mcg
Reporting group description	Participants received FF ELLIPTA 200 mcg 4 puffs PM as total daily dose for 7 days.
Reporting group title	FP 50 mcg
Reporting group description	Participants received FF DISKUS 50 mcg 1 puff PM as total daily dose for 7 days.
Reporting group title	FP 200 mcg
Reporting group description	Participants received FF DISKUS 100 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Reporting group title	FP 500 mcg
Reporting group description	Participants received FF DISKUS 250mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Reporting group title	FP 1000 mcg
Reporting group description	Participants received FF DISKUS 500 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Reporting group title	FP 2000 mcg
Reporting group description	Participants received FF DISKUS 500 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Reporting group title	BUD 100 mcg
Reporting group description	Participants received BUD Turbuhaler 100 mcg 1 puff PM as total daily dose for 7 days.
Reporting group title	BUD 400 mcg
Reporting group description	Participants received BUD Turbuhaler 200 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Reporting group title	BUD 800 mcg
Reporting group description	Participants received BUD Turbuhaler 400 mcg 1 puff AM and 1 puff PM as total daily dose for 7 days.
Reporting group title	BUD 1600 mcg
Reporting group description	Participants received BUD Turbuhaler 400 mcg 2 puff AM and 2 puff PM as total daily dose for 7 days.
Reporting group title	BUD 3200 mcg
Reporting group description	Participants received BUD Turbuhaler 400 mcg 4 puffs AM and PM as total daily dose for 7 days.
Serious adverse events Placebo FF 25 mcg FF 100 mcg FF 200 mcg FF 400 mcg FF 800 mcg FP 50 mcg FP 200 mcg FP 500 mcg FP 1000 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg BUD 3200 mcg Total subjects affected by serious adverse events      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      number of deaths (all causes) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0      number of deaths resulting from adverse events
Frequency threshold for reporting non-serious adverse events: 3%
Non-serious adverse events Placebo FF 25 mcg FF 100 mcg FF 200 mcg FF 400 mcg FF 800 mcg FP 50 mcg FP 200 mcg FP 500 mcg FP 1000 mcg FP 2000 mcg BUD 100 mcg BUD 400 mcg BUD 800 mcg BUD 1600 mcg BUD 3200 mcg Total subjects affected by non serious adverse events      subjects affected / exposed 10 / 17 (58.82%) 6 / 20 (30.00%) 8 / 19 (42.11%) 7 / 19 (36.84%) 6 / 18 (33.33%) 7 / 18 (38.89%) 10 / 21 (47.62%) 4 / 20 (20.00%) 4 / 20 (20.00%) 8 / 18 (44.44%) 6 / 17 (35.29%) 6 / 18 (33.33%) 8 / 18 (44.44%) 5 / 18 (27.78%) 6 / 18 (33.33%) 3 / 18 (16.67%) Vascular disorders Phlebitis      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 1 / 20 (5.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 Surgical and medical procedures Tooth repair      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 General disorders and administration site conditions Chest discomfort      subjects affected / exposed 2 / 17 (11.76%) 0 / 20 (0.00%) 0 / 19 (0.00%) 2 / 19 (10.53%) 0 / 18 (0.00%) 0 / 18 (0.00%) 2 / 21 (9.52%) 0 / 20 (0.00%) 0 / 20 (0.00%) 1 / 18 (5.56%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 4 0 0 2 0 0 2 0 0 1 0 0 0 1 0 0 Catheter site bruise      subjects affected / exposed 2 / 17 (11.76%) 0 / 20 (0.00%) 0 / 19 (0.00%) 1 / 19 (5.26%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 1 / 17 (5.88%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 2 0 0 1 0 0 1 0 0 0 1 0 1 0 0 0 Catheter site pain      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 2 / 18 (11.11%) 0 / 18 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 Catheter site related reaction      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 1 / 18 (5.56%) 1 / 17 (5.88%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 Catheter site swelling      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Fatigue      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 1 / 18 (5.56%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Feeling jittery      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Peripheral swelling      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 Vessel puncture site bruise      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Immune system disorders Seasonal allergy      subjects affected / exposed 1 / 17 (5.88%) 1 / 20 (5.00%) 1 / 19 (5.26%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 3 / 21 (14.29%) 1 / 20 (5.00%) 1 / 20 (5.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%)      occurrences all number 1 1 1 0 0 0 3 1 1 0 0 0 1 0 1 0 Reproductive system and breast disorders Dysmenorrhoea      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Genital discomfort      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 1 / 19 (5.26%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Respiratory, thoracic and mediastinal disorders Oropharyngeal pain      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 1 / 19 (5.26%) 0 / 19 (0.00%) 0 / 18 (0.00%) 2 / 18 (11.11%) 1 / 21 (4.76%) 0 / 20 (0.00%) 1 / 20 (5.00%) 2 / 18 (11.11%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%)      occurrences all number 0 0 1 0 0 3 1 0 1 2 0 0 0 0 1 0 Wheezing      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 2 / 21 (9.52%) 0 / 20 (0.00%) 1 / 20 (5.00%) 0 / 18 (0.00%) 1 / 17 (5.88%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 1 / 18 (5.56%)      occurrences all number 3 0 0 0 0 1 3 0 1 0 1 0 0 0 1 2 Cough      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 1 / 18 (5.56%) 1 / 17 (5.88%) 1 / 18 (5.56%) 1 / 18 (5.56%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 1 1 1 0 1 0 Asthma      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 1 / 19 (5.26%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%)      occurrences all number 0 0 0 1 0 0 1 0 0 0 0 0 1 0 1 0 Nasal congestion      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 20 (0.00%) 1 / 18 (5.56%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%)      occurrences all number 0 0 0 0 0 1 0 1 0 1 0 0 0 0 0 1 Rhinorrhoea      subjects affected / exposed 2 / 17 (11.76%) 0 / 20 (0.00%) 0 / 19 (0.00%) 1 / 19 (5.26%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 2 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 Dry throat      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sinonasal obstruction      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Sinus pain      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 1 / 19 (5.26%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Throat irritation      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Psychiatric disorders Anxiety      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Injury, poisoning and procedural complications Contusion      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 1 / 18 (5.56%) 1 / 17 (5.88%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 Arthropod bite      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Post-traumatic neck syndrome      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 1 / 18 (5.56%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 Scratch      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Skin abrasion      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 Nervous system disorders Headache      subjects affected / exposed 4 / 17 (23.53%) 5 / 20 (25.00%) 3 / 19 (15.79%) 1 / 19 (5.26%) 2 / 18 (11.11%) 1 / 18 (5.56%) 2 / 21 (9.52%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 2 / 17 (11.76%) 2 / 18 (11.11%) 2 / 18 (11.11%) 3 / 18 (16.67%) 3 / 18 (16.67%) 2 / 18 (11.11%)      occurrences all number 8 5 3 1 2 1 2 0 0 0 2 2 2 3 3 3 Dizziness      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 1 / 18 (5.56%) 1 / 18 (5.56%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 2 / 18 (11.11%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%)      occurrences all number 0 0 0 0 1 1 0 0 0 0 0 2 0 0 0 1 Dysgeusia      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 1 / 18 (5.56%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 1 Paraesthesia      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Syncope      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Eye disorders Eye swelling      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 1 / 19 (5.26%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Eyelid oedema      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 Gastrointestinal disorders Nausea      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 2 / 18 (11.11%) 1 / 18 (5.56%) 2 / 18 (11.11%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 1 0 2 1 2 Dry mouth      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 1 / 19 (5.26%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 1 0 0 0 1 Abdominal pain      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 1 / 18 (5.56%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 1 0 0 0 0 0 0 Diarrhoea      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 1 / 20 (5.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 Constipation      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 Dyspepsia      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Dysphagia      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Gastrooesophageal reflux disease      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Lip dry      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Saliva altered      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Skin and subcutaneous tissue disorders Eczema      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 1 / 19 (5.26%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Keloid scar      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 Rash      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 Skin discolouration      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Skin irritation      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 1 / 19 (5.26%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Musculoskeletal and connective tissue disorders Back pain      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 1 / 19 (5.26%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 1 / 18 (5.56%) 2 / 17 (11.76%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 0 1 2 0 0 0 0 0 Arthralgia      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 Pain in extremity      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 1 / 17 (5.88%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 Flank pain      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Musculoskeletal discomfort      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 1 / 17 (5.88%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 Musculoskeletal pain      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 Neck pain      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 Infections and infestations Nasopharyngitis      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 2 / 18 (11.11%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 1 / 17 (5.88%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 2 1 0 0 0 1 0 0 0 1 0 Rhinitis      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 1 / 19 (5.26%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 1 / 20 (5.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 Gastroenteritis      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 Urinary tract infection      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 1 / 17 (5.88%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 Vulvovaginal candidiasis      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 1 / 21 (4.76%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 Metabolism and nutrition disorders Decreased appetite      subjects affected / exposed 0 / 17 (0.00%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 1 / 18 (5.56%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 Gout      subjects affected / exposed 1 / 17 (5.88%) 0 / 20 (0.00%) 0 / 19 (0.00%) 0 / 19 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 21 (0.00%) 0 / 20 (0.00%) 0 / 20 (0.00%) 0 / 18 (0.00%) 0 / 17 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%) 0 / 18 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

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Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
16 Jan 2017	Amendment No. 1 was to clarify the doserationale, emergency unblinding procedure, and approval of substantial amendments procedure, as requested by the Medicines and Healthcare products Regulatory Agency(MHRA), as well as to clarify the blood sample time points and volumes and update the medical monitor contact details.
03 Oct 2017	Amendment No. 2 The protocol design, to allow participants to complete either 1 or 2 treatment periods.To allow recruitment of participants taking low dose inhaled corticosteroids (ICS) with appropriate washout period. To allow inclusion of light smokers.Removal of the Run-in and treatment period 2 baseline visits for AMP challenge. To allow the subjects to leave the unit after Day 7 evening procedures. To allow in-stream data review.Changes laid down in memorandum (MEMOs) to protocol amendment 1 were also incorporated into this protocol amendment.
26 Apr 2018	Amendment No. 3 is being issued to update the SAE contact and processing information, the pregnancy reporting timelines, as well as to include administrative changes clarifying the screening PEFR procedure.
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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