A Randomised, Double Blind, Placebo Controlled, 4 Period, Incomplete Block, Crossover Study Assessing the Dose-response Curve of Fluticasone Propionate in an Antigen Challenge Chamber

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00848965
• Collaborator: (none)
• Enrollment: 59
• Location: 1
• Arms: 5
• Duration (Months): 3
• Patients Per Site Per Month: 19.5

Study Details

Study Description

Brief Summary

This is a single-centre, randomised, double-blind, four-period, incomplete block, crossover study, with 8 days repeat dosing of intranasal Fluticasone Propionate (25, 50, 100, 200ug) and/or placebo in the Vienna Challenge Chamber in subjects with allergic rhinitis.

Condition or Disease	Intervention/Treatment	Phase
Rhinitis, Allergic, Perennial; Allergic Rhinitis	Drug: Fluticasone propionate; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double Blind, Placebo Controlled, 4 Period, Incomplete Block, Crossover Study to Assess the Dose-response Curve of Intranasal Fluticasone Propionate (25, 50, 100 and 200 μg, Once Daily for 8 Days) in the Vienna Challenge Chamber for the Purpose of Investigating the Sensitivity
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo comparator
Experimental: Fluticasone propionate 25ug	Drug: Fluticasone propionate; Corticosteriod, with anti-inflammatory effects
Experimental: Fluticason propionate 50ug	Drug: Fluticasone propionate; Corticosteriod, with anti-inflammatory effects
Experimental: Fluticasone propionate 100ug	Drug: Fluticasone propionate; Corticosteriod, with anti-inflammatory effects
Experimental: Flutciasone propionate 200ug	Drug: Fluticasone propionate; Corticosteriod, with anti-inflammatory effects

Outcome Measures

Primary Outcome Measures

1. Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC) [Day 8 of each study period (Periods 1-4); up to Day 158]

   The TNSS (score of 0-12), defined as the sum of the symptom scores for nasal obstruction, rhinorrhea, nasal itch, and sneeze (each scored on 0-3 scale [0=none, 1=mild, 2=moderate, 3=severe]) was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours PSC. In the VCC, aerosolized allergen is administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. Weighted mean TNSS was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.

Secondary Outcome Measures

1. Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) [Day 8 of each study period (Periods 1-4); up to Day 158]

   Allergic rhinitis decreases the passage of air through the nose (nasal airflow) by increasing the nasal airway resistance. Rhinomanometry is used as an objective measurement of airway resistance. Nasal airflow was measured using active anterior rhinomanometry at pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of VCC. Weighted mean nasal airflow was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.

2. Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) [Day 8 of each study period (Periods 1-4); up to Day 158]

   Nasal secretion was measured by weighing tissues used by participants. Wet tissue weight assessments were made pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of challenge chamber throughout the study. Weighted mean nasal secretion was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.

3. Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge) [Day 8 of each study period (Periods 1-4); up to Day 158]

   The eye symptom score (total score of 0 [none] to 9 [severe]) was calculated as the sum of the symptom scores for watery eyes, itchy eyes, and red eyes, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), and was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours post-start of challenge chamber. Weighted mean eye symptom score was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.

4. Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge) [Day 8 of each study period (Periods 1-4); up to Day 158]

   GSS (total score=0-30) is calculated as the sum of sneeze, nasal itch, rhinorrhea, nasal obstruction, cough, itchy throat, itchy ears, watery eyes, itchy eyes, and red eyes SSs, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), as was measured at pre-challenge, and then every 15 mins from 0.25 to 4 hours post-start of challenge chamber. Weighted mean global symptom score was evaluated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.

5. Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2 [Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158]

   AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction [PCR] products) messenger ribonucleic acid (mRNA) biomarker expression data for CCL2, a steroid-responsive gene. Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used. CCL2 data are presented by period to show the treatment-by-period interaction. ng, nanograms.

6. Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2 [Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158]

   AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction [PCR] products) messenger ribonucleic acid (mRNA) biomarker expression data for 7 steroid-responsive genes (DUSP_1_TI, FKBP5, GILZ, PLAU, CCL2, PTGS2, and RGS2) and 3 housekeeping reference genes (GAPDH, 18S, and b-actin). Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The subject is healthy with the exception of seasonal allergic rhinitis. Healthy as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests, cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures.

• Males and females who are aged between 18 and 65 years of age.

A female is eligible to enter and participate in the study if she is of:

1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post menopausal. For the purposes of this study, post menopausal is defined as 1 year without menses (FSH/LH will be also tested to confirm menopausal status); or

2. Child bearing potential, has a negative pregnancy test (urine) at entry, and agrees to one of the following acceptable contraceptive methods when used consistently and correctly (i.e., in accordance with the approved product label and the instructions of a physician for the duration of the study - screening visit to follow-up contact):

• Complete abstinence from intercourse from the first visit, throughout the trial and for a minimum of 7 days after the completion of the trial; or

• Male partner was sterile prior to the female subject's entry into the study, or

• Implants of levonorgestrel inserted for at least 1 month prior to the study

• Injectable progestogen administered for at least 1 month prior to the study

• Oral contraceptive (combined or progestogen only) administered for a least one monthly cycle prior to study medication administration; or

• The contraceptive transdermal patch, such as norelgestromin / ethinyl estradiol transdermal system (if the subject is less than 89kg); or

• Double-barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm .

• Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; or

• An intrauterine device (IUD) or intrauterine system (IUS), inserted by a qualified physician,

• Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 12 month period preceding the screening visit and who have a pack history of less than 10 pack years.

Pack years = Number of cigarettes per day x Number of years smoked 20

• They exhibit a moderate response to up to 1500 grass pollen grains/m3 after 2 hours in the Vienna Challenge Chamber, which is defined as a nasal symptom score of at least 6. (Nasal symptom score is the sum of nasal obstruction, rhinorrhoea, nasal itch and sneeze, each of which are scored on a scale from 0 to 3)

• They have a positive skin prick test (wheal ³ 4mm) for grass pollen at or within the 12 months preceding the screening visit.

• They have a positive RAST (Radioallergosorbent Test) (³ class 2) for grass pollen at or within the 12 months preceding the screening visit.

• They have a TNSS score (Total Nasal Symptom Score)of less than 3 and a score of no more than 1 for any single symptom of the TNSS prior to the screening allergen challenge.

• There are no conditions or factors that would make the subject unlikely to be able to stay in the trial

• Able to provide written informed consent.

• The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.

• Demonstrated ability to use the intranasal device in a satisfactory and repeatable manner.

Exclusion Criteria:

• As a result of medical interview, physical examination or screening investigations, the principle investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 150 mmHg or a diastolic pressure above 90 mmHg unless the Investigator confirms that it is satisfactory for their age.

• The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness.

• Pregnant or nursing females.

• Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception as outlined (Inclusion Criteria 2)

• On examination the subject is found to have any structural nasal abnormalities or nasal polyposis, a history of frequent nosebleeds, recent nasal surgery or recent (within 2 weeks) or ongoing upper respiratory tract infection which in the Responsible Physician's opinion renders the subject unsuitable for participation in the study.

• Any respiratory disease other than mild stable asthma that is controlled with occasional use of as-needed short-acting beta-agonists and associated with normal lung function.

• The subject is likely to be unable to abstain from salbutamol use for 8 hours before a challenge.

• The subject has a screening QTcB value >450msec (based on single or average QTc value of triplicate ECGs obtained over a brief recording period), PQ interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave). In addition subjects will be excluded if they have a history of atrial or ventricular arrhythmia.

• The subject has a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.

• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation.

• The subject has taken prescription or non-prescription drugs, within 7 days prior to the first dose of study medication, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety.

• History of alcohol/drug abuse or dependence within 12 months of the study. Abuse of alcohol defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine).

• The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• The subject has donated a unit of blood (450 mL) within the previous 16 weeks or intends to donate within 16 weeks after completing the study.

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.

• The subject has tested positive for HIV antibodies (if tested according to site Standard Operating Procedures).

• The subject has a positive pre-study urine drug/ urine alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids (THC) and Benzodiazepines.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Vienna		Austria	A-1150

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00848965
• Other Study ID Numbers: 110341; 781 IIa
• First Posted: Feb 23, 2009
• Last Update Posted: Sep 24, 2012
• Last Verified: Feb 1, 2011

• Keywords provided by GlaxoSmithKline: fluticasone propionate; Vienna Challenge Chamber; glucocorticosteroids; allergic rhinitis
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Fluticasone; Xhance

Study Results

Participant Flow

Pre-assignment Detail	Participants (par.) were randomized to receive treatment in one of five sequences in four study periods: ABCD, EABC, DEAB, CDEA, BCDE (A, Placebo; B, fluticasone propionate [FP] 25 micrograms [µg]: C, FP 50 µg; D, FP 100 µg; E, FP 200 µg). One par. randomized to ABCD withdrew due to an adverse event; one par. randomized to EABC withdrew consent.

Arm/Group Title	Placebo/FP 25, 50, 100, 200 µg
Arm/Group Description	Participants received placebo/fluticasone propionate (FP) in a dose of 25, 50, 100, and 200 micrograms (µg) once daily as 1 nasal spray into each nostril from 2 separate devices for 8 days each, in a crossover design. Treatment was given in one of five sequences in Periods 1, 2, 3, and 4 (with a minimum of a 14-day washout period between treatments): ABCD, EABC, DEAB, CDEA, and BCDE (A, Placebo; B, FP 25 µg: C, FP 50 µg; D, FP 100 µg; E, FP 200 µg). On Day 8 of each treatment period (1 hour post-dose), participants entered the Vienna Challenge Chamber (VCC) for a 4-hour period, and the assessments were conducted 2-5 hours post-dose. All participants attended a follow-up visit within 2 to 4 weeks after their final dose, and the overall duration for participation in the study (screening to follow-up) did not exceed 158 days.
Period Title: Overall Study
STARTED	59
COMPLETED	57
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Placebo/FP 25, 50, 100, 200 µg
Arm/Group Description	Participants received placebo/fluticasone propionate (FP) in a dose of 25, 50, 100, and 200 micrograms (µg) once daily as 1 nasal spray into each nostril from 2 separate devices for 8 days each, in a crossover design. Treatment was given in one of five sequences in Periods 1, 2, 3, and 4 (with a minimum of a 14-day washout period between treatments): ABCD, EABC, DEAB, CDEA, and BCDE (A, Placebo; B, FP 25 µg: C, FP 50 µg; D, FP 100 µg; E, FP 200 µg). On Day 8 of each treatment period (1 hour post-dose), participants entered the Vienna Challenge Chamber (VCC) for a 4-hour period, and the assessments were conducted 2-5 hours post-dose. All participants attended a follow-up visit within 2 to 4 weeks after their final dose, and the overall duration for participation in the study (screening to follow-up) did not exceed 158 days.
Overall Participants	59
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	27.2 (5.30)
Sex: Female, Male (Count of Participants)
Female	30 50.8%
Male	29 49.2%
Race/Ethnicity, Customized (participants) [Number]
Japanese/East Asian Heritage (EAH)/South EAH	1 1.7%
White	58 98.3%

Outcome Measures

1. Primary Outcome

Title	Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC)
Description	The TNSS (score of 0-12), defined as the sum of the symptom scores for nasal obstruction, rhinorrhea, nasal itch, and sneeze (each scored on 0-3 scale [0=none, 1=mild, 2=moderate, 3=severe]) was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours PSC. In the VCC, aerosolized allergen is administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. Weighted mean TNSS was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time Frame	Day 8 of each study period (Periods 1-4); up to Day 158

Outcome Measure Data

Analysis Population Description

All Subjects Population: all participants randomized to receive at least one dose of study treatment. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	Placebo	25 µg FP	50 µg FP	100 µg FP	200 µg FP
Arm/Group Description	Participants received identical placebo once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 25 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 50 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 100 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 200 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days
Measure Participants	46	44	46	46	46
Mean (Standard Deviation) [scores on a scale]	7.17 (2.912)	5.54 (2.437)	5.66 (2.280)	5.29 (2.218)	4.77 (2.433)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, 25 µg FP
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.38
	Confidence Interval	(2-Sided) 95%; -2.08 to -0.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.350
	Estimation Comments	Treatment difference (FP minus placebo) is presented as the difference in the adjusted means for treatment versus placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, 50 µg FP
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.55
	Confidence Interval	(2-Sided) 95%; -2.16 to -0.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.309
	Estimation Comments	Treatment difference (FP minus placebo) is presented as the difference in the adjusted means for treatment versus placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, 100 µg FP
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.72
	Confidence Interval	(2-Sided) 95%; -2.33 to -1.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.305
	Estimation Comments	Treatment difference (FP minus placebo) is presented as the difference in the adjusted means for treatment versus placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, 200 µg FP
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.90
	Confidence Interval	(2-Sided) 95%; -2.60 to -1.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.351
	Estimation Comments	Treatment difference is presented as the difference in the adjusted means for treatment versus placebo.

2. Secondary Outcome

Title	Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)
Description	Allergic rhinitis decreases the passage of air through the nose (nasal airflow) by increasing the nasal airway resistance. Rhinomanometry is used as an objective measurement of airway resistance. Nasal airflow was measured using active anterior rhinomanometry at pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of VCC. Weighted mean nasal airflow was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time Frame	Day 8 of each study period (Periods 1-4); up to Day 158

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	Placebo	25 µg FP	50 µg FP	100 µg FP	200 µg FP
Arm/Group Description	Participants received identical placebo once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 25 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 50 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 100 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 200 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days
Measure Participants	46	44	46	46	46
Mean (Standard Deviation) [Milliliters per second (mL/s)]	335.20 (145.373)	368.66 (144.230)	375.94 (142.105)	362.59 (142.216)	411.65 (160.148)

3. Secondary Outcome

Title	Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)
Description	Nasal secretion was measured by weighing tissues used by participants. Wet tissue weight assessments were made pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of challenge chamber throughout the study. Weighted mean nasal secretion was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time Frame	Day 8 of each study period (Periods 1-4); up to Day 158

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	Placebo	25 µg FP	50 µg FP	100 µg FP	200 µg FP
Arm/Group Description	Participants received identical placebo once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 25 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 50 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 100 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 200 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days
Measure Participants	46	44	46	46	46
Mean (Standard Deviation) [grams (g)]	2.43 (2.203)	1.63 (1.893)	1.43 (1.458)	1.26 (1.550)	1.02 (1.271)

4. Secondary Outcome

Title	Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)
Description	The eye symptom score (total score of 0 [none] to 9 [severe]) was calculated as the sum of the symptom scores for watery eyes, itchy eyes, and red eyes, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), and was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours post-start of challenge chamber. Weighted mean eye symptom score was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time Frame	Day 8 of each study period (Periods 1-4); up to Day 158

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	Placebo	25 µg FP	50 µg FP	100 µg FP	200 µg FP
Arm/Group Description	Participants received identical placebo once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 25 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 50 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 100 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 200 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days
Measure Participants	46	44	46	46	46
Mean (Standard Deviation) [scores on a scale]	2.35 (2.240)	1.52 (1.678)	1.44 (1.711)	1.93 (1.726)	1.41 (1.491)

5. Secondary Outcome

Title	Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge)
Description	GSS (total score=0-30) is calculated as the sum of sneeze, nasal itch, rhinorrhea, nasal obstruction, cough, itchy throat, itchy ears, watery eyes, itchy eyes, and red eyes SSs, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), as was measured at pre-challenge, and then every 15 mins from 0.25 to 4 hours post-start of challenge chamber. Weighted mean global symptom score was evaluated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time Frame	Day 8 of each study period (Periods 1-4); up to Day 158

Outcome Measure Data

Analysis Population Description

All Subjects Population. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	Placebo	25 µg FP	50 µg FP	100 µg FP	200 µg FP
Arm/Group Description	Participants received identical placebo once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 25 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 50 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 100 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 200 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days
Measure Participants	46	44	46	46	46
Mean (Standard Deviation) [scores on a scale]	11.14 (5.407)	8.17 (4.302)	8.24 (4.231)	8.69 (4.346)	7.13 (3.487)

6. Secondary Outcome

Title	Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2
Description	AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction [PCR] products) messenger ribonucleic acid (mRNA) biomarker expression data for CCL2, a steroid-responsive gene. Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used. CCL2 data are presented by period to show the treatment-by-period interaction. ng, nanograms.
Time Frame	Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158

Outcome Measure Data

Analysis Population Description

All Subjects Population. The data presented for each period are an average of the data collected on Day 1 and Day 8 of each period. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	Placebo	25 µg FP	50 µg FP	100 µg FP	200 µg FP
Arm/Group Description	Participants received identical placebo once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 25 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 50 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 100 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 200 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days
Measure Participants	12	12	12	12	12
Period 1, n=12, 12, 12, 11, 11	12396.08096	1377.248941	1231.251053	3340.460181	3377.403394
Period 2, n=11, 11, 11, 12, 11	4206.320679	2192.232108	1765.627412	2342.488506	2821.11204
Period 3, n=11, 11, 11, 12, 12	4135.167835	3612.444351	2184.76185	1229.316666	2505.03196
Period 4, n=12, 11, 11, 11, 12	10111.38124	3523.276415	2615.352938	1917.918706	1071.598621

7. Secondary Outcome

Title	Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2
Description	AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction [PCR] products) messenger ribonucleic acid (mRNA) biomarker expression data for 7 steroid-responsive genes (DUSP_1_TI, FKBP5, GILZ, PLAU, CCL2, PTGS2, and RGS2) and 3 housekeeping reference genes (GAPDH, 18S, and b-actin). Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used.
Time Frame	Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158

Outcome Measure Data

Analysis Population Description

All Subjects Population. The data presented are an average of the data collected on Day 1 and Day 8 of each treatment period. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	Placebo	25 µg FP	50 µg FP	100 µg FP	200 µg FP
Arm/Group Description	Participants received identical placebo once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 25 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 50 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 100 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days	Participants received FP in a dose of 200 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days
Measure Participants	46	45	45	46	46
18S	6439292568	6109603485	5822423622	6218835383	6222906532
B-actin	1978137.142	1481307.983	1629006.342	1630387.679	1543748.32
DUSP_1_T1	107004.8077	104633.517	107031.4158	118158.2593	113323.9632
FKBP5	28739.3975	155791.0745	174963.5715	177935.1307	151362.3934
GAPDH	5776051.293	6143058.472	6451580.253	6008446.351	5972472.493
GILZ	13601.9459	26629.75763	29304.22353	28832.53255	27304.24721
PLAU	26364.53138	18550.2079	18810.56868	20918.214	21692.66346
PTGS2	42479.35246	31120.01509	35049.7556	38443.85612	33657.71928
RGS2	55084.11432	45255.7763	54186.44212	50507.30739	50373.91657

Adverse Events

Adverse Event Reporting Description	Serious adverse events (SAEs) and non-serious AEs were collected in the 46 participants who received placebo and FP 25, 50, and 100 µg treatments, and in the 47 participants who received FP 200 µg.
Arm/Group Title	Placebo		25 µg FP		50 µg FP		100 µg FP		200 µg FP
Arm/Group Description	Participants received identical placebo once daily as 1 nasal spray into each nostril from separate devices for 8 days		Participants received FP in a dose of 25 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days		Participants received FP in a dose of 50 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days		Participants received FP in a dose of 100 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days		Participants received FP in a dose of 200 µg once daily as 1 nasal spray into each nostril from separate devices for 8 days
All Cause Mortality
	Placebo		25 µg FP		50 µg FP		100 µg FP		200 µg FP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		25 µg FP		50 µg FP		100 µg FP		200 µg FP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/47 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		25 µg FP		50 µg FP		100 µg FP		200 µg FP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/46 (8.7%)		6/46 (13%)		3/46 (6.5%)		2/46 (4.3%)		1/47 (2.1%)
Blood and lymphatic system disorders
Iron deficiency anemia	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/47 (0%)
Ear and labyrinth disorders
Ear pain	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/47 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/47 (0%)
Nausea	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/47 (0%)
Vomiting	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/47 (0%)
Infections and infestations
Nasopharygitis	1/46 (2.2%)		2/46 (4.3%)		0/46 (0%)		0/46 (0%)		1/47 (2.1%)
Bronchitis bacterial	0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/47 (0%)
Nervous system disorders
Headache	3/46 (6.5%)		3/46 (6.5%)		1/46 (2.2%)		0/46 (0%)		0/47 (0%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		1/46 (2.2%)		0/47 (0%)
Cough	0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/47 (0%)
Rhinorrhea	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/47 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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