Intranasal SB-705498 in Allergic Rhinitis (AR) Patients

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01424397
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 4
• Actual Duration (Months): 2.8
• Patients Per Site Per Month: 25.4

Study Details

Study Description

Brief Summary

This study is designed to look at the affect of SB-705498 on allergic rhinitis symptoms induced by an allergen chamber challenge.

Condition or Disease	Intervention/Treatment	Phase
Rhinitis	Drug: SB-705498; Drug: FP; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo Controlled, Incomplete Block, 3 Way Cross Over Study in Subjects With Allergic Rhinitis to Assess the Effect of Intranasal Repeat Doses of SB-705498 When Administered Alone or in Conjunction With Intranasal Fluticasone Propionate on the Symptoms of Rhinitis in the Vienna Allergen Challenge Chamber
• Actual Study Start Date: Apr 14, 2011
• Actual Primary Completion Date: Jul 7, 2011
• Actual Study Completion Date: Jul 7, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SB-705498 Experimental	Drug: SB-705498; 12mg intranasal
Active Comparator: Fluticasone Propionate Active Comparator	Drug: FP; 200ug intranasal
Placebo Comparator: Placebo Placebo Comparator	Drug: placebo; placebo intranasal
Experimental: SB-705498+FP Experimental	Drug: SB-705498; 12mg intranasal; Drug: FP; 200ug intranasal

Outcome Measures

Primary Outcome Measures

1. Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8 [Day 8 of each treatment period]

   Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Weighted mean (WM) of TNSS and its individual components (nasal congestion, rhinorrhoea, itching and sneezing) are presented on Day 8. Weighted mean was calculated over the time interval 0 to 4 hours after start of allergen chamber challenge by calculating the area under the curve of TNSS/component from time of the first observation to time of the last observation (AUC [tf-t1 hours]) using the trapezoidal rule, and then dividing by the actual relevant time interval (tf-t1) required by participant to complete the chamber challenge assessments. A Bayesian analysis was conducted to derive the posterior probability for TNSS.

Secondary Outcome Measures

1. Mean TNSS and Its Individual Components From Day 4 to Day 8 [pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on Day 8 of each treatment period]

   Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Mean of TNSS and its individual components is presented pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on Day 8.

2. Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR) [Day 8]

   Total Nasal Airflow is calculated as the sum of the left nostril and the right nostril airflow values. AAR is a very sensitive method of assessing clinical parameters of nasal obstruction (nasal flow, nasal resistance and nasal flow increase). A participant was instructed to breathe through one nostril while a sensor in the other nostril measured the difference in pre-nasal and choanal pressure. The system was connected to a computer. Nasal flow and nasal resistance were observed at pressure levels of 75, 150 and 300 Pascal. The defined measuring range for the flow was +-1000 milliliter per second (mL/s). Weighted means for total nasal airflow Resistance was calculated by dividing the area under the curve between 1 and 4 hours (via the linear trapezoidal method) by the total duration that the participant took to complete the chamber challenge assessments.

3. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo [Day 8]

   The RQLQ composed of 28 items covering 7 domains of health. Each question is scored on a scale of 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). 7 domains were: Activities (3 items):1, 2, 3;Sleep (3 items): 4, 5, 6; Non-nose/eye symptoms (7 items): 7, 8, 9, 10, 11, 12, 13; Practical Problems (3 items): 14, 15, 16; Nasal Symptoms (4 items): 17, 18, 19, 20; Eye Symptoms (4 items): 21, 22, 23, 24; Emotional (4 items): 25, 26, 27, 28 consisted of total 28 items. Domain activity score = total post-baseline score for individualized activity items answered on both visits divided by total Baseline score for individualized activity items answered on both visits multiplied by the Baseline score for item(s) missing post-baseline. The global RQLQ score was calculated by averaging all 28 item scores, which ranges from 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). Higher scores indicate worsening of symptoms.

4. Area Under Concentration-time Curve (AUC) for SB-705498 on Day 8 [Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h)]

   Plasma samples for pharmacokinetic (PK) analysis were drawn at indicated time points of each treatment period. AUC0-t was calculated by the linear trapezoidal method. AUC0-infinity was calculated as the sum of the AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant, where first-order elimination or terminal rate constant was calculated from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the last three (or more) non-zero plasma concentrations. Values were reported as Least Squares Geometric Means with respective % CV.

5. Maximum Observed Concentration (Cmax) for SB-705498 on Day 8 [Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h)]

   Plasma samples for pharmacokinetic analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as least squares geometric means with respective geometric coefficient of variation (% CV).

6. Number of Participants With Vital Signs of Potential Clinical Importance (PCI) [Up to Week 16]

   Vital signs assessment included heart rate, blood pressure, and temperature. Criteria for vital sign values meeting potential clinical concern included: systolic blood pressure (SBP) <85 and >160 millimeters of mercury (mm Hg), diastolic blood pressure (DBP) < 45 and > 100 mm Hg, temperature <36 and >37.5 Degree Celsius and heart Rate <40 and >110 beats per minute. Only parameters with PCI values are reported.

7. Change From Baseline in ECG Values: Heart Rate [Baseline and Day 8 of each treatment period]

   Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, and QTc intervals. Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value.

8. Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF [Baseline and Day 8 of each treatment period]

   Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, QTc corrected by Bazett's formula (QTcB) and QTc corrected by Fridericia's formula (QTcF). Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value.

9. Number of Participants With Hematology Parameters of PCI [Up to Week 16]

   The PCC range for hematology parameters included white blood cell count, low: 0.67, high 1.82, neutrophil count, low: 0.83, Hemoglobin, male- high 1.03, female- high 1.13, hematocrit, male- high 1.02, female- high 1.17, Platelet Count, low: 0.67, high: 1.57, lymphocytes, low 0.81. Only parameters with PCI values are reported.

10. Number of Participants With Clinical Biochemistry Parameters of PCI [Up to Week 16]

    The PCC range for clinical chemistry parameters included albumin, low: 0.86, millimole per liter (mmol)/L, calcium, low: 0.91, high: 1.06, glucose. Low: 0.71, high: 1.41, Potassium, low: 0.86, high: 1.10, Sodium, low: 0.96, high: 1.03, Total CO2, Low: 0.86, high: 1.14, Creatinine, in male, Low: <75 micromole per liter (μmol/L), high: >110 μmol/L, female, Low: <65 μmol/L, high: >95, Blood Urea Nitrogen (BUN), high: >1.5xULN mmol/L, Uric Acid, in male, Low: < 180 μmol/L, high: > 480 μmol/L, female, Low: < 120 μmol/L, high: > 420. Only parameters with PCI values are reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Diagnosis of AR, as determined by the presence of rhinitis symptoms that last for several months per year, for more than 1 year and are not attributed to allergy, infections or nasal abnormalities.

2. TNSS score of >=4 following screening allergen challenge chamber.

3. Positive skin prick test for seasonal pollen

4. Positive RAST for seasonal pollen

5. Healthy as determined by responsible physician with the exception of mild asthma and AR

6. Male or female between 18 and 65 years of age inclusive.

7. A female subject is eligible to participate if she is of:

• Non-childbearing potential defined as pre-menopausal females with a \documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory].

• Child-bearing potential and agrees to use one of the contraception methods listed as instructed. Female subjects must agree to use contraception until 84 days post-last treatment administration.

1. Male subjects with female partners of child-bearing potential must agree to use one contraception as instructed. This must be followed from the time of the first dose of study medication until 84 days post-last treatment administration.

2. Body weight ≥ 50 kg (males) and ≥45kg (females) and BMI within the range 19 - 29.9 kg/m2 (inclusive).

3. Screening pre-challenge FEV1 greater than or equal to 80% and baselines FEV1/FVC greater than or equal to 70% of predicted value.

4. Capable of giving written informed consent.

5. Average QTcB, < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

6. AST and ALT < 2xULN; alkaline phosphatase and bilirubin less than or equal to 1.5xULN

Exclusion Criteria:

1. Nasal abnormalities likely to affect the outcome of the study,

2. History of frequent nosebleeds.

3. Respiratory disease other than mild asthma

4. A positive pre-study Hepatitis B or Hepatitis C result within 3 months of screening

5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities

6. Positive pre-study drug/alcohol/smoking screen.

7. A positive test for HIV antibody.

8. History of regular alcohol consumption within 6 months of the study defined as:

• An average weekly intake of >14 drinks for males or >7 drinks for females.

1. The subject has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product prior to D1.

2. Exposure to more than four new chemical entities within 12 months prior to D1.

3. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days prior to the first dose of study medication.

4. History of sensitivity to any of the study medications, or components

5. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

6. Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.

7. Lactating females.

8. Subject is mentally or legally incapacitated.

9. Urine cotinine levels indicative of smoking

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

Additional Information:

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

Publications

• Bareille P, Murdoch RD, Denyer J, Bentley J, Smart K, Yarnall K, Zieglmayer P, Zieglmayer R, Lemell P, Horak F. The effects of a TRPV1 antagonist, SB-705498, in the treatment of seasonal allergic rhinitis. Int J Clin Pharmacol Ther. 2013 Jul;51(7):576-84. doi: 10.5414/CP201890.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01424397
• Other Study ID Numbers: 111924; 2011-000115-11
• First Posted: Aug 29, 2011
• Last Update Posted: Sep 13, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic

Study Results

Participant Flow

Recruitment Details	A total of 70 male and female participants with a history of allergic rhinitis (AR) were enrolled in this study. Study period was 14 April 2011 to 07 July 2011.
Pre-assignment Detail	There were 3 study treatment periods each lasting 8 days separated by a washout of 14-20 days. Participants were randomized to 12 different sequences.

Arm/Group Title	Treatment A First, Then B, Then D	Treatment B First, Then A, Then D	Treatment B, Then D, Then A	Treatment A, Then D, Then B	Treatment D, Then A, Then B	Treatment D, Then B, Then A	Treatment A, Then B, Then C	Treatment B, Then A, Then C	Treatment B, Then C, Then A	Treatment A, Then C, Then B	Treatment C, Then A, Then B	Treatment C, Then B, Then A
Arm/Group Description	Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered once-daily (OD) in morning for 8 days and 4 actuations per nostril of placebo matching Fluticasone propionate (FP) alone were administered OD in evening for 7 days). Participants received FP 200 microgram (μg) alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received 12 milligrams (mg) SB-705498 co-administered with FP (Treatment D) in Period-3 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received Participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-3 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-2 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days).There was a 14-20 days washout between 2 treatment periods.	Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-2 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-1 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-1 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-3 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-3 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-2 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-2 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received SB-705498 12 mg alone (Treatment C) in Period-1 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received SB-705498 12 mg alone (Treatment C) in Period-1 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.
Period Title: Period-1 (8 Days)
STARTED	7	8	8	8	8	8	4	4	4	3	4	4
COMPLETED	7	8	8	8	8	8	4	4	4	3	4	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Period-1 (8 Days)
STARTED	7	8	8	8	8	8	4	4	4	3	4	4
COMPLETED	7	8	8	8	8	8	4	4	4	3	4	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Period-1 (8 Days)
STARTED	7	8	8	8	8	8	4	4	4	3	4	4
COMPLETED	7	8	7	8	8	8	4	4	4	3	4	4
NOT COMPLETED	0	0	1	0	0	0	0	0	0	0	0	0
Period Title: Period-1 (8 Days)
STARTED	7	8	7	8	8	8	4	4	4	3	4	4
COMPLETED	7	8	7	8	8	8	4	4	4	3	4	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Period-1 (8 Days)
STARTED	7	8	7	8	8	8	4	4	4	3	4	4
COMPLETED	7	8	7	8	8	8	4	4	4	3	4	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Treatment A First, Then B, Then D	Treatment B First, Then A, Then D	Treatment B, Then D, Then A	Treatment A, Then D, Then B	Treatment D, Then A, Then B	Treatment D, Then B, Then A	Treatment A, Then B, Then C	Treatment B, Then A, Then C	Treatment B, Then C, Then A	Treatment A, Then C, Then B	Treatment C, Then A, Then B	Treatment C, Then B, Then A	Total
Arm/Group Description	Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered once-daily (OD) in morning for 8 days and 4 actuations per nostril of placebo matching Fluticasone propionate (FP) alone were administered OD in evening for 7 days). Participants received FP 200 microgram (μg) alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received 12 milligrams (mg) SB-705498 co-administered with FP (Treatment D) in Period-3 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received Participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-3 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-2 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days).There was a 14-20 days washout between 2 treatment periods.	Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-2 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-1 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received 12 mg SB-705498 co-administered with FP (Treatment D) in Period-1 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-3 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-3 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received FP 200 μg alone (Treatment B) in Period-1 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-2 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received Placebo alone (treatment A) in period-1 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received SB-705498 12 mg alone (Treatment C) in Period-2 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received SB-705498 12 mg alone (Treatment C) in Period-1 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-2 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-3 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Eligible participants received SB-705498 12 mg alone (Treatment C) in Period-1 (4 actuations per nostril [each of 1.5mg] of 12 mg SB-705498 were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). Participants received FP 200 μg alone (Treatment B) in Period-2 (4 actuations per nostril of Placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril [each of 25μg] of FP 200 μg alone were administered OD in evening for 7 days). Participants received Placebo alone (treatment A) in period-3 (4 actuations per nostril of placebo matching SB-705498 alone were administered OD in morning for 8 days and 4 actuations per nostril of placebo matching FP alone were administered OD in evening for 7 days). There was a 14-20 days washout between 2 treatment periods.	Total of all reporting groups
Overall Participants	7	8	8	8	8	8	4	4	4	3	4	4	70
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	29.6 (5.65)	29.6 (9.24)	28.0 (5.07)	28.5 (9.20)	28.5 (6.46)	27.8 (6.34)	24.5 (3.11)	32.5 (10.54)	25.3 (1.50)	24.0 (1.00)	28.3 (6.29)	26.8 (11.03)	28.1 (6.86)
Sex: Female, Male (Count of Participants)
Female	4 57.1%	2 25%	6 75%	3 37.5%	4 50%	4 50%	2 50%	0 0%	4 100%	2 66.7%	1 25%	1 25%	33 47.1%
Male	3 42.9%	6 75%	2 25%	5 62.5%	4 50%	4 50%	2 50%	4 100%	0 0%	1 33.3%	3 75%	3 75%	37 52.9%
Race/Ethnicity, Customized (Count of Participants)
White(Wh)-Wh/Caucasian(Ca)/European(Eu)Heritage(H)	7 100%	8 100%	8 100%	7 87.5%	7 87.5%	7 87.5%	4 100%	4 100%	4 100%	3 100%	4 100%	4 100%	67 95.7%
American Indian or Alaskan Native Wh-Wh/Ca/Eu H	0 0%	0 0%	0 0%	0 0%	1 12.5%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
Wh - Arabic/North African H	0 0%	0 0%	0 0%	1 12.5%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%
Asian - South East Asian H	0 0%	0 0%	0 0%	0 0%	0 0%	1 12.5%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%

Outcome Measures

1. Primary Outcome

Title	Mean Total Nasal Symptom Score (TNSS) and Its Individual Components on Day 8
Description	Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Weighted mean (WM) of TNSS and its individual components (nasal congestion, rhinorrhoea, itching and sneezing) are presented on Day 8. Weighted mean was calculated over the time interval 0 to 4 hours after start of allergen chamber challenge by calculating the area under the curve of TNSS/component from time of the first observation to time of the last observation (AUC [tf-t1 hours]) using the trapezoidal rule, and then dividing by the actual relevant time interval (tf-t1) required by participant to complete the chamber challenge assessments. A Bayesian analysis was conducted to derive the posterior probability for TNSS.
Time Frame	Day 8 of each treatment period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	FP 200 μg	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	68	69	23	46
TNSS WM	6.53 (2.300)	3.65 (2.360)	6.57 (2.418)	4.14 (2.243)
Nasal congestion scoreWM	1.80 (0.653)	1.15 (0.792)	1.82 (0.648)	1.18 (0.715)
Rhinorrhoea score WM	1.67 (0.693)	0.94 (0.726)	1.75 (0.697)	1.05 (0.687)
Nasal itching score WM	1.67 (0.760)	0.94 (0.708)	1.57 (0.886)	1.17 (0.699)
Sneezing score WM	1.39 (0.763)	0.62 (0.573)	1.43 (0.785)	0.74 (0.560)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FP 200 μg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Bayesian analysis: The posterior probability of a reduction in TNSS with FP alone compared to Placebo using Mixed Models Analysis was 1.0000

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SB-705498 12 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Bayesian analysis: The posterior probability of a reduction in TNSS with SB-705498 alone compared to Placebo using Mixed Models Analysis was 0.7127

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SB-705498 + FP 12 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Bayesian analysis: The posterior probability of a reduction in TNSS with SB-705498 + FP compared to Placebo using Mixed Models Analysis was 1.0000

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FP 200 μg, SB-705498 + FP 12 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Bayesian analysis: The posterior probability of a reduction in TNSS with SB-705498 + FP compared to FP alone using Mixed Models Analysis was 0.0160

2. Secondary Outcome

Title	Mean TNSS and Its Individual Components From Day 4 to Day 8
Description	Nasal symptoms (nasal congestion, rhinorrhoea, itching and sneezing) were scored on a scale from 0 to 3 where 0= absent symptoms, 3 = severe symptoms. TNSS was calculated as the sum of the response for all 4 individual nasal symptom scores. TNSS ranged from 0 to 12, where 0=absent symptoms, 3=severe symptoms. Higher the score, more severe the symptoms. Mean of TNSS and its individual components is presented pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on Day 8.
Time Frame	pre-evening (pm) dose on Days 4, 5, 6, 7 and pre-challenge [1 hour (hr)] on Day 8 of each treatment period

Outcome Measure Data

Analysis Population Description

All subjects population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	Placebo	FP 200 μg	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	68	69	23	47
TNSS,Day 4, pre-pm dose	3.6 (2.47)	2.4 (2.20)	3.3 (2.65)	2.6 (1.94)
TNSS,Day 5, pre-pm dose	3.6 (2.58)	2.0 (2.24)	2.9 (2.60)	2.3 (2.10)
TNSS,Day 6, pre-pm dose	3.3 (2.45)	1.8 (2.03)	2.8 (2.74)	2.0 (2.03)
TNSS,Day 7, pre-pm dose	3.2 (2.26)	1.7 (1.90)	2.2 (2.37)	1.9 (2.12)
TNSS,Day 8, pre-challenge (1hr)	2.0 (1.88)	1.3 (1.60)	1.9 (1.52)	1.1 (1.45)
Nasal congestion score code,Day 4, pre-pm dose	1.0 (0.81)	0.8 (0.69)	0.9 (0.95)	0.7 (0.65)
Nasal congestion score code,Day 5, pre-pm dose	0.9 (0.82)	0.7 (0.70)	0.7 (0.88)	0.6 (0.64)
Nasal congestion score code,Day 6, pre-pm dose	0.9 (0.80)	0.7 (0.74)	0.8 (0.83)	0.6 (0.68)
Nasal congestion score code,Day 7, pre-pm dose	0.8 (0.69)	0.6 (0.62)	0.7 (0.82)	0.6 (0.65)
Nasal congestion score code,Day 8, pre-challenge	0.7 (0.67)	0.6 (0.67)	0.6 (0.59)	0.4 (0.58)
Rhinorrhoea score code,Day 4, pre-pm dose	0.9 (0.71)	0.6 (0.76)	0.9 (0.87)	0.5 (0.65)
Rhinorrhoea score code,Day 5, pre-pm dose	0.9 (0.75)	0.5 (0.78)	0.9 (0.90)	0.5 (0.66)
Rhinorrhoea score code,Day 6, pre-pm dose	0.8 (0.73)	0.4 (0.65)	0.8 (0.90)	0.6 (0.62)
Rhinorrhoea score code,Day 7, pre-pm dose	0.8 (0.65)	0.4 (0.62)	0.6 (0.78)	0.4 (0.69)
Rhinorrhoea score code,Day 8, pre-challenge (1hr)	0.6 (0.69)	0.3 (0.59)	0.6 (0.66)	0.3 (0.50)
Nasal itching score code,Day 4, pre-pm dose	0.9 (0.85)	0.5 (0.66)	0.7 (0.71)	0.7 (0.71)
Nasal itching score code,Day 5, pre-pm dose	0.8 (0.81)	0.4 (0.63)	0.4 (0.66)	0.7 (0.75)
Nasal itching score code,Day 6, pre-pm dose	0.8 (0.84)	0.3 (0.58)	0.5 (0.73)	0.5 (0.72)
Nasal itching score code,Day 7, pre-pm dose	0.8 (0.80)	0.4 (0.62)	0.3 (0.65)	0.5 (0.72)
Nasal itching score code,Day 8, pre-challenge (1hr	0.5 (0.65)	0.3 (0.60)	0.3 (0.49)	0.3 (0.55)
Sneezing score code,Day 4, pre-pm dose	0.9 (0.78)	0.5 (0.68)	0.9 (0.87)	0.6 (0.68)
Sneezing score code,Day 5, pre-pm dose	0.9 (0.85)	0.4 (0.67)	0.8 (0.83)	0.4 (0.65)
Sneezing score code,Day 6, pre-pm dose	0.8 (0.82)	0.4 (0.57)	0.7 (0.92)	0.4 (0.68)
Sneezing score code,Day 7, pre-pm dose	0.8 (0.75)	0.3 (0.55)	0.5 (0.73)	0.4 (0.61)
Sneezing score code,Day 8, pre-challenge (1hr)	0.3 (0.51)	0.1 (0.26)	0.4 (0.58)	0.1 (0.31)

3. Secondary Outcome

Title	Total Nasal Airflow on Day 8 Measured Using Active Anterior Rhinomanometry (AAR)
Description	Total Nasal Airflow is calculated as the sum of the left nostril and the right nostril airflow values. AAR is a very sensitive method of assessing clinical parameters of nasal obstruction (nasal flow, nasal resistance and nasal flow increase). A participant was instructed to breathe through one nostril while a sensor in the other nostril measured the difference in pre-nasal and choanal pressure. The system was connected to a computer. Nasal flow and nasal resistance were observed at pressure levels of 75, 150 and 300 Pascal. The defined measuring range for the flow was +-1000 milliliter per second (mL/s). Weighted means for total nasal airflow Resistance was calculated by dividing the area under the curve between 1 and 4 hours (via the linear trapezoidal method) by the total duration that the participant took to complete the chamber challenge assessments.
Time Frame	Day 8

Outcome Measure Data

Analysis Population Description

All subjects population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	Placebo	FP 200 μg	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	69	70	23	46
Least Squares Mean (Standard Error) [Milliliters per second (mL/s)]	306.99 (17.255)	388.34 (17.207)	299.68 (22.806)	379.40 (18.783)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FP 200 μg
	Comments	Placebo versus FP 200 μg,Nasal Airflow resistance Total WM,0-4 hr
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	81.35
	Confidence Interval	(2-Sided) 90%; 60.54 to 102.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.560
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SB-705498 12 mg
	Comments	Placebo versus FP 12 mg SB-705498 , Nasal Airflow resistance Total WM, 0-4 hr
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-7.31
	Confidence Interval	(2-Sided) 90%; -39.7 to 25.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.548
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SB-705498 + FP 12 mg
	Comments	Placebo versus SB-705498 + FP 12 mg, Nasal Airflow resistance Total WM, 0-4 hr
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	72.40
	Confidence Interval	(2-Sided) 90%; 48.28 to 96.52
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.567
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FP 200 μg, SB-705498 + FP 12 mg
	Comments	FP 200 μg versus SB-705498 + FP 12 mg, Nasal Airflow resistance Total WM, 0-4 hr
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.95
	Confidence Interval	(2-Sided) 90%; -33.1 to 15.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.592
	Estimation Comments

4. Secondary Outcome

Title	Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) Following Repeat Doses of SB-705498 or or SB-705498 Matching Placebo
Description	The RQLQ composed of 28 items covering 7 domains of health. Each question is scored on a scale of 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). 7 domains were: Activities (3 items):1, 2, 3;Sleep (3 items): 4, 5, 6; Non-nose/eye symptoms (7 items): 7, 8, 9, 10, 11, 12, 13; Practical Problems (3 items): 14, 15, 16; Nasal Symptoms (4 items): 17, 18, 19, 20; Eye Symptoms (4 items): 21, 22, 23, 24; Emotional (4 items): 25, 26, 27, 28 consisted of total 28 items. Domain activity score = total post-baseline score for individualized activity items answered on both visits divided by total Baseline score for individualized activity items answered on both visits multiplied by the Baseline score for item(s) missing post-baseline. The global RQLQ score was calculated by averaging all 28 item scores, which ranges from 0 to 6 (where, 0 = not troubled and 6 = extremely troubled). Higher scores indicate worsening of symptoms.
Time Frame	Day 8

Outcome Measure Data

Analysis Population Description

All subjects population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	Placebo	FP 200 μg	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	69	70	23	46
Least Squares Mean (Standard Error) [Score on a scale]	1.67 (0.119)	0.99 (0.118)	1.66 (0.177)	1.14 (0.135)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FP 200 μg
	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 (Net)
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 90%; -0.87 to -0.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.113
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, SB-705498 12 mg
	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 (Net)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 90%; -0.30 to 0.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.173
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, SB-705498 + FP 12 mg
	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 (Net)
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 90%; -0.74 to -0.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.130
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FP 200 μg, SB-705498 + FP 12 mg
	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 (Net)
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 90%; -0.06 to 0.37
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.130
	Estimation Comments

5. Secondary Outcome

Title	Area Under Concentration-time Curve (AUC) for SB-705498 on Day 8
Description	Plasma samples for pharmacokinetic (PK) analysis were drawn at indicated time points of each treatment period. AUC0-t was calculated by the linear trapezoidal method. AUC0-infinity was calculated as the sum of the AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant, where first-order elimination or terminal rate constant was calculated from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the last three (or more) non-zero plasma concentrations. Values were reported as Least Squares Geometric Means with respective % CV.
Time Frame	Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h)

Outcome Measure Data

Analysis Population Description

The 'Pharmacokinetic Population' is defined as participants in the 'All Subjects' population for whom a pharmacokinetic sample was obtained and analyzed. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	23	46
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour per mililiter (ng.h/mL)]	588.26 (71.4)	608.84 (74.2)

6. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) for SB-705498 on Day 8
Description	Plasma samples for pharmacokinetic analysis were drawn at indicated time points of each treatment period. Cmax was defined as maximal measured plasma concentration over the time span specified. Values were reported as least squares geometric means with respective geometric coefficient of variation (% CV).
Time Frame	Period 1: Day 1 (post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h), Period 2 and 3: Day 1 (Pre-dose 0.0 h, post dose 1 and 5 h) and 8 (Pre-dose (0.0 h), post dose 1 and 5 h)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	23	46
Geometric Mean (Geometric Coefficient of Variation) [nanograms per mililiter (ng/mL)]	145.958 (68.8)	154.231 (71.0)

7. Secondary Outcome

Title	Number of Participants With Vital Signs of Potential Clinical Importance (PCI)
Description	Vital signs assessment included heart rate, blood pressure, and temperature. Criteria for vital sign values meeting potential clinical concern included: systolic blood pressure (SBP) <85 and >160 millimeters of mercury (mm Hg), diastolic blood pressure (DBP) < 45 and > 100 mm Hg, temperature <36 and >37.5 Degree Celsius and heart Rate <40 and >110 beats per minute. Only parameters with PCI values are reported.
Time Frame	Up to Week 16

Outcome Measure Data

Analysis Population Description

All Subjects population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	Placebo	FP 200 μg	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	68	69	23	46
Temperature,Low,period 3	2 28.6%	0 0%	0 0%	0 0%
Temperature,Low,Follow up	2 28.6%	1 12.5%	0 0%	0 0%

8. Secondary Outcome

Title	Change From Baseline in ECG Values: Heart Rate
Description	Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, and QTc intervals. Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value.
Time Frame	Baseline and Day 8 of each treatment period

Outcome Measure Data

Analysis Population Description

All subjects population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	Placebo	FP 200 μg	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	68	69	23	46
Mean (Standard Deviation) [beats per minute (bpm)]	-0.2 (11.32)	-4.7 (10.80)	-4.8 (8.09)	-2.6 (11.19)

9. Secondary Outcome

Title	Change From Baseline in ECG Values: PR Interval, QRS Duration, QT Interval, QTcB, QTcF
Description	Single 12-lead ECGs were obtained at each time point during the study using an ECG machine that automatically calculated heart rate and measured PQ, QRS, QT, QTc corrected by Bazett's formula (QTcB) and QTc corrected by Fridericia's formula (QTcF). Baseline was assessment on Day 1. Change from Baseline was the values at specified time points subtracted by the Baseline value.
Time Frame	Baseline and Day 8 of each treatment period

Outcome Measure Data

Analysis Population Description

All subjects population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	Placebo	FP 200 μg	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B
Measure Participants	68	69	23	46
PR Interval	2.7 (8.31)	-1.2 (9.38)	4.5 (9.29)	0.4 (9.73)
QRS Duration	0.8 (6.30)	2.2 (5.52)	0.8 (5.92)	-0.2 (5.05)
QT Interval	-1.5 (21.47)	4.6 (22.12)	-0.3 (17.50)	2.5 (17.93)
QTcB	-3.6 (17.30)	-9.3 (18.44)	-13.9 (20.79)	-4.1 (21.10)
QTcF	-2.9 (13.16)	-4.4 (13.37)	-9.0 (16.53)	-1.9 (13.33)

10. Secondary Outcome

Title	Number of Participants With Hematology Parameters of PCI
Description	The PCC range for hematology parameters included white blood cell count, low: 0.67, high 1.82, neutrophil count, low: 0.83, Hemoglobin, male- high 1.03, female- high 1.13, hematocrit, male- high 1.02, female- high 1.17, Platelet Count, low: 0.67, high: 1.57, lymphocytes, low 0.81. Only parameters with PCI values are reported.
Time Frame	Up to Week 16

Outcome Measure Data

Analysis Population Description

All subjects population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	Placebo	FP 200 μg	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	68	69	23	46
Total Neutrophils,low	7 100%	9 112.5%	2 25%	4 50%
Hematocrit,high	0 0%	0 0%	1 12.5%	0 0%
Hemoglobin,high	0 0%	0 0%	1 12.5%	0 0%

11. Secondary Outcome

Title	Number of Participants With Clinical Biochemistry Parameters of PCI
Description	The PCC range for clinical chemistry parameters included albumin, low: 0.86, millimole per liter (mmol)/L, calcium, low: 0.91, high: 1.06, glucose. Low: 0.71, high: 1.41, Potassium, low: 0.86, high: 1.10, Sodium, low: 0.96, high: 1.03, Total CO2, Low: 0.86, high: 1.14, Creatinine, in male, Low: <75 micromole per liter (μmol/L), high: >110 μmol/L, female, Low: <65 μmol/L, high: >95, Blood Urea Nitrogen (BUN), high: >1.5xULN mmol/L, Uric Acid, in male, Low: < 180 μmol/L, high: > 480 μmol/L, female, Low: < 120 μmol/L, high: > 420. Only parameters with PCI values are reported.
Time Frame	Up to Week 16

Outcome Measure Data

Analysis Population Description

All subjects population. Only those participants available at the indicated time points were analyzed.

Arm/Group Title	Placebo	FP 200 μg	SB-705498 12 mg	SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.	Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.	Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
Measure Participants	68	69	23	46
Creatinine,Low	19 271.4%	25 312.5%	6 75%	14 175%
Creatinine,High	2 28.6%	2 25%	1 12.5%	2 25%
Aspartate Amino Transferase,High	1 14.3%	1 12.5%	1 12.5%	0 0%
Potassium,High	2 28.6%	4 50%	2 25%	5 62.5%
Uric acid,High	1 14.3%	0 0%	1 12.5%	1 12.5%
Gamma Glutamyl Transferase,High	1 14.3%	1 12.5%	2 25%	1 12.5%
Total Bilirubin,High	1 14.3%	1 12.5%	1 12.5%	1 12.5%
Alanine Amino Transferase,High	0 0%	2 25%	0 0%	0 0%

Adverse Events

Time Frame	Non-SAEs and SAEs were collected from start of the treatment up to Week 16.
Adverse Event Reporting Description	All subject population was used for collection of adverse events
Arm/Group Title	Placebo		FP 200 μg		SB-705498 12 mg		SB-705498 + FP 12 mg
Arm/Group Description	Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.		Participants administered matching placebo for SB-705498 once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B. Each spray of FP delivered approximately 25μg per actuation.		Participants administered SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and matching placebo for FP once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.		Participants received SB-705498 12 mg once-daily in the form of Intranasal suspension four actuations in each nostril for 8 days in morning using Device A and FP 200 μg once-daily in the form of Intranasal spray four actuations in each nostril in evening for 7 days using Device B.
All Cause Mortality
	Placebo		FP 200 μg		SB-705498 12 mg		SB-705498 + FP 12 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/69 (0%)		0/23 (0%)		0/47 (0%)
Serious Adverse Events
	Placebo		FP 200 μg		SB-705498 12 mg		SB-705498 + FP 12 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		0/69 (0%)		0/23 (0%)		0/47 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		FP 200 μg		SB-705498 12 mg		SB-705498 + FP 12 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/68 (35.3%)		28/69 (40.6%)		13/23 (56.5%)		19/47 (40.4%)
Eye disorders
Conjunctivitis	0/68 (0%)		0/69 (0%)		0/23 (0%)		1/47 (2.1%)
Eye irritation	1/68 (1.5%)		0/69 (0%)		0/23 (0%)		0/47 (0%)
Gastrointestinal disorders
Toothache	1/68 (1.5%)		1/69 (1.4%)		0/23 (0%)		0/47 (0%)
Diarrhoea	0/68 (0%)		0/69 (0%)		1/23 (4.3%)		0/47 (0%)
Vomiting	0/68 (0%)		0/69 (0%)		1/23 (4.3%)		0/47 (0%)
General disorders
Pyrexia	0/68 (0%)		1/69 (1.4%)		1/23 (4.3%)		0/47 (0%)
Immune system disorders
Hypersensitivity	12/68 (17.6%)		11/69 (15.9%)		7/23 (30.4%)		10/47 (21.3%)
Food allergy	0/68 (0%)		1/69 (1.4%)		0/23 (0%)		0/47 (0%)
Infections and infestations
Nasopharyngitis	1/68 (1.5%)		1/69 (1.4%)		1/23 (4.3%)		1/47 (2.1%)
Influenza	0/68 (0%)		2/69 (2.9%)		0/23 (0%)		1/47 (2.1%)
Oral herpes	1/68 (1.5%)		0/69 (0%)		0/23 (0%)		0/47 (0%)
Urinary tract infection	0/68 (0%)		1/69 (1.4%)		0/23 (0%)		0/47 (0%)
Injury, poisoning and procedural complications
Procedural pain	0/68 (0%)		1/69 (1.4%)		0/23 (0%)		0/47 (0%)
Nervous system disorders
Headache	9/68 (13.2%)		11/69 (15.9%)		5/23 (21.7%)		5/47 (10.6%)
Migraine	0/68 (0%)		1/69 (1.4%)		0/23 (0%)		0/47 (0%)
Respiratory, thoracic and mediastinal disorders
Nasal discomfort	3/68 (4.4%)		2/69 (2.9%)		0/23 (0%)		0/47 (0%)
Cough	1/68 (1.5%)		0/69 (0%)		0/23 (0%)		1/47 (2.1%)
Dysphonia	0/68 (0%)		1/69 (1.4%)		0/23 (0%)		0/47 (0%)
Epistaxis	0/68 (0%)		1/69 (1.4%)		0/23 (0%)		0/47 (0%)
Oropharyngeal pain	0/68 (0%)		0/69 (0%)		0/23 (0%)		1/47 (2.1%)
Pharyngeal inflammation	0/68 (0%)		1/69 (1.4%)		0/23 (0%)		0/47 (0%)
Rhinitis allergic	1/68 (1.5%)		0/69 (0%)		0/23 (0%)		0/47 (0%)
Sneezing	1/68 (1.5%)		0/69 (0%)		0/23 (0%)		0/47 (0%)
Throat irritation	0/68 (0%)		0/69 (0%)		0/23 (0%)		1/47 (2.1%)

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.