A Comparator Study of Fluticasone Propionate Nasal Spray Verses (vs) Cetirizine in the Treatment of Seasonal Allergic Rhinitis

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01916226
• Collaborator: (none)
• Enrollment: 682
• Locations: 31
• Arms: 4
• Duration (Months): 2.5
• Patients Per Site: 22
• Patients Per Site Per Month: 8.7

Study Details

Study Description

Brief Summary

This phase IV investigational trial is being conducted to evaluate the efficacy of a 2-week treatment of fluticasone propionate nasal spray (FPNS) vs. cetirizine on allergic nasal and ocular symptoms and quality of life in adult subjects with SAR. It is hypothesized that FPNS provides greater nasal symptom relief than cetirizine. The primary measure used to test this hypothesis is the change from baseline over two weeks in reflective total nasal symptom score (rTNSS) compared between FPNS and cetirizine. Approximately 648 subjects will be randomized into a 1:1:1:1 ratio of treatment allocation across approximately twenty-five to thirty-five sites in the US during the 2013 fall allergy season. All subjects will be outpatients. The total duration of study will be approximately 21 days including 7 days of screening period, and 14 days of treatment period.

Condition or Disease	Intervention/Treatment	Phase
Rhinitis, Allergic, Perennial and Seasonal	Drug: FPNS; Drug: FPNS Placebo; Drug: Cetirizine; Drug: Cetirizine Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 682 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Study 200165, A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Compare the Efficacy of a 2-Week Treatment With Fluticasone Propionate Nasal Spray Versus Cetirizine in Adult Subjects With Seasonal Allergic Rhinitis (SAR)
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 17, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FPNS arm Subject will receive two sprays (200 mcg per day)of FP into each nostril once daily (OD) every morning for 14 days	Drug: FPNS; Bottled, 16 gm net fill weight for 120 metered sprays with unit dose strength of 50 mcg per spray.
Placebo Comparator: FPNS Placebo arm Subject will receive two sprays of FP placebo into each nostril OD every morning for 14 days	Drug: FPNS Placebo; Bottled placebo nasal spray (vehicle for Fluticasone propionate aqueous nasal spray), 16 gm net fill weight for 120 metered sprays.
Experimental: Cetirizine arm Subject will receive Cetirizine capsule by mouth OD in the morning for 14 days	Drug: Cetirizine; Over-encapsulated Cetirizine tablet with unit dose strength of 10 mg in High Density Poly Ethylene Bottles (20 count per bottle).
Placebo Comparator: Cetirizine Placebo arm Subject will receive Cetirizine Placebo capsule by mouth OD in the morning for 14 days	Drug: Cetirizine Placebo; Over-encapsulated Cetirizine matching tablet High Density Poly Ethylene Bottles (20 count per bottle).

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline (CFB) in the Individual AM Reflective Total Nasal Symptom Scores (rTNSS) Over the Entire Treatment Period [Baseline through the entire treatment period (2 weeks)]

   The rTNSS score is the sum of the four individual symptom scores for rhinorrhea, nasal congestion, nasal itching, and sneezing. Each symptom is scored on a scale ranging from 0 to 3; the rTNSS ranges from 0 (none) to 12 (severe). Each individual symptom was evaluated using a scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The reflective assessment of the TNSS scores the four nasal symptoms over the previous 24 hours. The participants themselves scored nasal symptoms in an e-diary. Baseline is defined as the arithmetic average of the rTNSS recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days. Change from Baseline was thus calculated as the 2-week average minus the Baseline value.

Secondary Outcome Measures

1. Mean Change From Baseline in the Individual AM Reflective Nasal Symptom Scores for Rhinorrhea, Nasal Congestion, Nasal Itching, and Sneezing Over the Entire Treatment Period [Baseline through the entire treatment period (2 weeks)]

   Each individual symptom was evaluated using a scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe).The reflective assessment scores the four nasal symptoms over the previous 24 hours. The participants themselves scored nasal symptoms in an e-diary. Baseline is defined as the arithmetic average of the individual AM reflective nasal symptom scores recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days. Change from Baseline was thus calculated as the 2-week average minus the Baseline value.

2. Mean Change From Baseline in the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) Overall Score at Visit 3/Early Withdrawal. [Baseline and Visit 3 (Study Day 14 +/- 2 days)/Early Withdrawal]

   The NRQLQ is a 16-item, validated, self-administered, disease (allergic rhinitis)-specific quality of life instrument that measures the functional problems most troublesome to participants with nocturnal allergy symptoms over a one-week interval. Each question is scored on a 7-point scale from 0 (not troubled) to 6 (extremely troubled). Items are grouped into four domains: sleep problems (4 items), sleep time problems (5 items), symptoms on waking in the morning (4 items), and practical problems (3 items). An overall score was calculated from the individual item scores. All items are weighted equally. A mean score is calculated across all items within each domain. The overall score is the mean across all items and ranges from 0 (not troubled) to 6 (extremely troubled). Higher scores reflect a lower quality of life. Change from Baseline was calculated as the 2-week average minus the Baseline value.

3. Mean Change From Baseline in the AM Pre-dose Instantaneous Total Nasal Symptom Score (iTNSS) Over the Entire Treatment Period [Baseline through the entire treatment period (2 weeks)]

   The iTNSS score is the sum of the four individual symptom scores for rhinorrhea, nasal congestion, nasal itching, and sneezing. Each symptom is scored on a scale ranging from 0 to 3; the iTNSS ranges from 0 (none) to 12 (severe). The symptoms were evaluated using a scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The instantaneous assessment of the TNSS scores the four nasal symptoms at the time of the assessment, or at that "instant." The participants themselves scored nasal symptoms in an e-diary once each morning prior to administering study drug. Baseline is defined as the arithmetic average of the iTNSS recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days.

4. Mean Change From Baseline in the AM Pre-dose Reflective Total Ocular Symptom Score (rTOSS) Over the Entire Treatment Period [Baseline through the entire treatment period (2 weeks)]

   The rTOSS is an eye assessment that comprises the sum of the three symptom scores for tearing/watering, itching/burning, and eye redness. Each symptom is scored on a scale of 0 to 3: 0, none; 1, mild; 2, moderate; 3, severe. The rTOSS ranges from 0 (none) to 9 (severe). The reflective assessment scores the participants' ocular symptoms over the preceding 24 hours. The participants themselves scored ocular symptoms in an e-diary. Baseline arithmetic is defined as the average of the rTNSS recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days. Change from Baseline was thus calculated as the 2-week average minus the Baseline value.

5. Mean Change From Baseline in the AM Pre-dose Instantaneous Total Ocular Symptom Score (iTOSS) Over the Entire Treatment Period [Baseline through the entire treatment period (2 weeks)]

   The iTOSS is an eye assessment that comprises the sum of the three symptom scores for tearing/watering, itching/burning, and eye redness. Each symptom is scored on a scale of 0 to 3: 0, none; 1, mild; 2, moderate; 3, severe. The iTOSS ranges from 0 (none) to 9 (severe). The instantaneous assessment scores the participants' ocular symptoms at the time of the assessment, or at that "instant." The participants themselves scored ocular symptoms in an e-diary once each morning prior to administering study drug. Baseline is defined as the arithmetic average of the iTOSS recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days. Change from Baseline was thus calculated as the 2-week average minus the Baseline value.

6. Mean Change From Baseline in the Combined Nasal and Ocular Reflective Total Symptom Score (rTSS = rTNSS+rTOSS) Over the Entire Treatment Period [Baseline through the entire treatment period (2 weeks)]

   The rTSS is the sum of the rTNSS and the rTOSS. The rTNSS score is the sum of the four individual symptom scores for rhinorrhea, nasal congestion, nasal itching, and sneezing. Each symptom is scored on a scale ranging from 0 to 3; the rTNSS ranges from 0 (none) to 12 (severe). Each individual symptom was evaluated using a scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The rTOSS assessment is comprised of the sum of the three symptom scores for tearing/watering, itching/burning, and eye redness. Each symptom is scored on a scale of 0 to 3: 0, none; 1, mild; 2, moderate; or 3, severe. The rTOSS ranges from 0 (none) to 9 (severe). The reflective assessment scores participants' symptoms over the previous 24 hours. The participants themselves scored nasal and ocular symptoms in an e-diary. Baseline is defined as the arithmetic average of the rTSS recorded on the morning of randomization and on each of the six preceding days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Informed consent: Subject must give their signed and dated written informed consent to participate. Subject must understand and be willing, able, and likely to comply with study procedures and restrictions. Subject must be able to read, comprehend, and record information in English.

• Subject is treatable on an outpatient basis.

• Age: >=18 years of age at Visit 1.

• Gender: Male or eligible female subjects. A female subject is eligible to participate if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, history of vasomotor symptoms. OR Childbearing potential with a negative pregnancy test at screening and agreeable to using one of the acceptable contraceptive methods consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study). An eligible female is also not lactating nor planning on becoming pregnant during the study.

• Diagnosis of SAR, defined as documented clinical history or physician verification of subject reported historical SAR during each of the last two fall allergy seasons and a positive skin prick test (wheal >=3 millimeter [mm] larger than the negative control) to a prevalent local fall allergen within 12 months prior to Visit 1 or at Visit 1.

• Adequate exposure to local fall pollen: Subject resides within a geographical region where exposure to the local fall pollen to which they are sensitized is expected to be moderate or greater during the study period. Subject does not plan to travel outside the geographical region where exposure to local fall pollen to which they are sensitized is expected to be moderate or greater for more than 48 hours during the study period.

At Visit 2, the subject must meet the following criteria

• Eligible subjects will need to have moderate to severe SAR symptoms, defined as a morning rTNSS of >=7 on at least four of the last seven days leading up to randomization. This includes the AM assessment on the morning of the randomization visit at Visit 2.

• Subjects should demonstrate at least a 70% compliance rate with both their placebo run-in study medications and their e-diary completion prior to randomization. This period includes the day of Visit 1 until the day before randomization at Visit 2.

• Subjects should have no significant change in medical condition(s) that would have been exclusionary at Visit 1.

• Subjects should not have used any prohibited medications that are detailed in the inclusion/exclusion criteria (including prohibited allergy medications).

• Subjects should not have travelled outside the local pollen region for more than 48 hours during the run-in period.

Exclusion Criteria

• Significant concomitant medical conditions, defined as but not limited to:

Historical or current evidence of a clinically significant uncontrolled disease of any body system (e.g., tuberculosis, psychological disorders, eczema, uncontrolled asthma). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or which would confound the interpretation of the study results if the disease/condition exacerbated during the study.

A severe physical obstruction of the nose (e.g., deviated septum or nasal polyp) or nasal septal perforation that could affect the deposition of intranasal study drug.

Nasal (e.g., nasal septum), ocular, or throat injury, or surgery to these areas in the last 3 months.

Rhinitis medicamentosa. Bacterial or viral infection (e.g., common cold) of the eyes or upper respiratory tract within two weeks of Visit 1 or during the screening period.

Documented evidence of acute or significant chronic sinusitis, as determined by the individual investigator.

Current or history of glaucoma and/or cataracts or ocular herpes simplex. Physical impairment that would affect subject's ability to safely and fully participate in the study.

Clinical evidence of a Candida infection of the nose. History of psychiatric disease, intellectual deficiency, poor motivation, substance abuse (including drug and alcohol) or other conditions that will limit the validity of informed consent or that would confound the interpretation of the study results.

History of adrenal insufficiency.

• Use of corticosteroids, defined as: Intranasal corticosteroid within four weeks prior to Visit 1 and during the treatment period. Inhaled, oral, intramuscular, intravenous, ocular, and/or dermatological corticosteroid (with the exception of hydrocortisone cream/ointment, 1% or less) within eight weeks prior to Visit 1 and during the treatment period.

• Use of allergy medications, within a timeframe relative to Visit 1, that would prevent the medication from being eliminated and/or have an effect. Exclusionary timeframes relative to Visit 1 for five common allergy treatments are noted below Intranasal cromolyn (<=2 weeks from Visit 1). Intranasal or systemic decongestants (<=3 days from Visit 1). Intranasal or systemic (other than oral) antihistamines (<=3 days from Visit 1).

Leukotriene modifiers (<=3 days from Visit 1). Oral antihistamines (<=2 days from Visit 1). Allergy medications, other than study supplied medications, are not allowed during the study.

• Use of other medications that may affect allergic rhinitis or its symptoms, e.g., use of any ocular antihistamines, artificial tears, eyewashes/nasal irrigation solutions, homeopathic preparations, lubricants, sympathomimetic or vasoconstrictor preparations during the screening and treatment periods

• Use of any medications (prescription or non-prescription) or alcohol to induce sleep 48-hours prior to Visit 1 and during the treatment period.

• Use of other intranasally administered medications (e.g., calcitonin), including herbals and homeopathics during the run-in (Visit 1 - Visit 2) and treatment period.

• Use of immunosuppressive medications within 8 weeks prior to screening and during the treatment period.

• Use of any medications that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4 (e.g., ritonavir, ketoconazole) during the run-in (Visit 1 - Visit 2) and treatment period.

• Known hypersensitivity to corticosteroids or any excipients present in the nasal spray.

• Known hypersensitivity to cetirizine or any excipients in the tablet.

• Recent exposure to an investigational study drug or device within 30 days of Visit 1.

• Affiliation with investigator site: Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study.

• Chickenpox or measles during the last 3 weeks prior to screening and is non-immune.

• Immunotherapy is exclusionary unless the immunotherapy was initiated >=30 days from Visit 1 and if the dose has remained fixed over the 30 days prior to Visit 1, and the dose will remain fixed for the duration of the study.

• Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirement.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Little Rock	Arkansas	United States	72205
2	GSK Investigational Site	Denver	Colorado	United States	80230
3	GSK Investigational Site	Aventura	Florida	United States	33180
4	GSK Investigational Site	Miami	Florida	United States	33173
5	GSK Investigational Site	Indianapolis	Indiana	United States	46208
6	GSK Investigational Site	Lenexa	Kansas	United States	66215
7	GSK Investigational Site	Overland Park	Kansas	United States	66210
8	GSK Investigational Site	Owensboro	Kentucky	United States	42301
9	GSK Investigational Site	Baltimore	Maryland	United States	21236
10	GSK Investigational Site	Bethesda	Maryland	United States	20814
11	GSK Investigational Site	North Dartmouth	Massachusetts	United States	02747
12	GSK Investigational Site	Ypsilanti	Michigan	United States	48197
13	GSK Investigational Site	Minneapolis	Minnesota	United States	55402
14	GSK Investigational Site	Columbia	Missouri	United States	65203
15	GSK Investigational Site	Rolla	Missouri	United States	65401
16	GSK Investigational Site	Saint Louis	Missouri	United States	63141
17	GSK Investigational Site	Bellevue	Nebraska	United States	68123-4303
18	GSK Investigational Site	Canton	Ohio	United States	44718
19	GSK Investigational Site	Cincinnati	Ohio	United States	45231
20	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73120
21	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15212
22	GSK Investigational Site	Orangeburg	South Carolina	United States	29118
23	GSK Investigational Site	Spartanburg	South Carolina	United States	29303
24	GSK Investigational Site	Austin	Texas	United States	78731
25	GSK Investigational Site	Austin	Texas	United States	78750
26	GSK Investigational Site	Dallas	Texas	United States	75246
27	GSK Investigational Site	Kerrville	Texas	United States	78028
28	GSK Investigational Site	San Antonio	Texas	United States	78229
29	GSK Investigational Site	Waco	Texas	United States	76712
30	GSK Investigational Site	South Burlington	Vermont	United States	05403
31	GSK Investigational Site	Greenfield	Wisconsin	United States	53228

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

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01916226
• Other Study ID Numbers: 200165
• First Posted: Aug 5, 2013
• Last Update Posted: Jun 20, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: cetirizine; seasonal allergic rhinitis; Quality of Life; fluticasone propionate nasal spray
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Rhinitis, Allergic, Perennial; Cetirizine

Study Results

Participant Flow

Recruitment Details	In anticipation of a 5% to 8% dropout rate, this study planned enrolment of 156 participants per treatment group in order to target 144 participants per treatment group, who would provide a full 2 weeks' worth of data.
Pre-assignment Detail	A total of 978 participants were screened for this study. Of these, 73 were pre-screen failures and 223 were screening/run-in failures. A total of 682 participants were randomized (1:1:1:1 ratio) to receive study treatment.

Arm/Group Title	FPNS 200 μg	Cetirizine 10 mg	FPNS Matching Placebo	Cetirizine Matching Placebo
Arm/Group Description	Participants self-administered fluticasone propionate nasal spray (FPNS) 200 micrograms (µg) per day as two sprays in each nostril (50 μg per spray) once daily in the morning (AM) for 2 weeks.	Participants self-administered a 10 milligram (mg) cetrizine capsule once daily in the AM for 2 weeks.	Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.	Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.
Period Title: Overall Study
STARTED	170	170	171	171
COMPLETED	169	169	168	167
NOT COMPLETED	1	1	3	4

Baseline Characteristics

Arm/Group Title	FPNS 200 μg	Cetirizine 10 mg	FPNS Matching Placebo	Cetirizine Matching Placebo	Total
Arm/Group Description	Participants self-administered FPNS 200 µg per day as two sprays in each nostril (50 μg per spray) once daily in the AM for 2 weeks.	Participants self-administered a 10 mg cetrizine capsule once daily in the AM for 2 weeks.	Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.	Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.	Total of all reporting groups
Overall Participants	170	170	171	171	682
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.1 (10.66)	39.2 (11.41)	41.3 (11.29)	40.4 (11.84)	40.3 (11.31)
Sex: Female, Male (Count of Participants)
Female	96 56.5%	113 66.5%	110 64.3%	109 63.7%	428 62.8%
Male	74 43.5%	57 33.5%	61 35.7%	62 36.3%	254 37.2%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	34 20%	20 11.8%	31 18.1%	35 20.5%	120 17.6%
American Indian or Alaska Native	1 0.6%	0 0%	1 0.6%	1 0.6%	3 0.4%
Asian - Central/South Asian Heritage	2 1.2%	2 1.2%	5 2.9%	3 1.8%	12 1.8%
Asian-East Asian Heritage	1 0.6%	0 0%	1 0.6%	0 0%	2 0.3%
Asian - South East Asian Heritage	2 1.2%	0 0%	1 0.6%	2 1.2%	5 0.7%
White - Arabic/North African Heritage	1 0.6%	0 0%	1 0.6%	1 0.6%	3 0.4%
White - White/Caucasian/European Heritage	129 75.9%	142 83.5%	128 74.9%	127 74.3%	526 77.1%
Mixed Race	0 0%	6 3.5%	3 1.8%	1 0.6%	10 1.5%
Not Captured by Study Site	0 0%	0 0%	0 0%	1 0.6%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline (CFB) in the Individual AM Reflective Total Nasal Symptom Scores (rTNSS) Over the Entire Treatment Period
Description	The rTNSS score is the sum of the four individual symptom scores for rhinorrhea, nasal congestion, nasal itching, and sneezing. Each symptom is scored on a scale ranging from 0 to 3; the rTNSS ranges from 0 (none) to 12 (severe). Each individual symptom was evaluated using a scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The reflective assessment of the TNSS scores the four nasal symptoms over the previous 24 hours. The participants themselves scored nasal symptoms in an e-diary. Baseline is defined as the arithmetic average of the rTNSS recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days. Change from Baseline was thus calculated as the 2-week average minus the Baseline value.
Time Frame	Baseline through the entire treatment period (2 weeks)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who were randomized and received at least one dose of study medication. Change from Baseline was analyzed for only those participants who were available for assessment at Baseline and at Weeks 1 and 2.

Arm/Group Title	FPNS 200 μg	Cetirizine 10 mg	FPNS Matching Placebo	Cetirizine Matching Placebo
Arm/Group Description	Participants self-administered FPNS 200 µg per day as two sprays in each nostril (50 μg per spray) once daily in the AM for 2 weeks	Participants self-administered a 10 mg cetrizine capsule once daily in the AM for 2 weeks.	Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.	Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.
Measure Participants	169	169	171	171
Mean (Standard Error) [Scores on a scale]	-2.2 (0.19)	-1.9 (0.18)	-1.5 (0.18)	-0.9 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FPNS 200 μg, Cetirizine 10 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments	Estimating the standard deviation of CFB in rTNSS over 2 weeks to be approximately 2.6, a two-sample t-test with α=0.05 suggests that a sample size of 144 participants per arm would provide 90% power to show a difference of 1.0 between treatments.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.7 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: -0.3
	Estimation Comments

2. Secondary Outcome

Title	Mean Change From Baseline in the Individual AM Reflective Nasal Symptom Scores for Rhinorrhea, Nasal Congestion, Nasal Itching, and Sneezing Over the Entire Treatment Period
Description	Each individual symptom was evaluated using a scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe).The reflective assessment scores the four nasal symptoms over the previous 24 hours. The participants themselves scored nasal symptoms in an e-diary. Baseline is defined as the arithmetic average of the individual AM reflective nasal symptom scores recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days. Change from Baseline was thus calculated as the 2-week average minus the Baseline value.
Time Frame	Baseline through the entire treatment period (2 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population. Change from Baseline was analyzed for only those participants who were available for assessment at Baseline and at Weeks 1 and 2.

Arm/Group Title	FPNS 200 μg	Cetirizine 10 mg	FPNS Matching Placebo	Cetirizine Matching Placebo
Arm/Group Description	Participants self-administered FPNS 200 µg per day as two sprays in each nostril (50 μg per spray) once daily in the AM for 2 weeks.	Participants self-administered a 10 mg cetrizine capsule once daily in the AM for 2 weeks.	Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.	Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.
Measure Participants	169	169	171	171
Nasal congestion	-0.5 (0.05)	-0.4 (0.04)	-0.3 (0.05)	-0.2 (0.04)
Nasal itching	-0.6 (0.05)	-0.5 (0.05)	-0.4 (0.05)	-0.2 (0.04)
Runny nose	-0.5 (0.05)	-0.4 (0.05)	-0.4 (0.05)	-0.3 (0.05)
Sneezing	-0.6 (0.05)	-0.6 (0.05)	-0.4 (0.05)	-0.2 (0.05)

3. Secondary Outcome

Title	Mean Change From Baseline in the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) Overall Score at Visit 3/Early Withdrawal.
Description	The NRQLQ is a 16-item, validated, self-administered, disease (allergic rhinitis)-specific quality of life instrument that measures the functional problems most troublesome to participants with nocturnal allergy symptoms over a one-week interval. Each question is scored on a 7-point scale from 0 (not troubled) to 6 (extremely troubled). Items are grouped into four domains: sleep problems (4 items), sleep time problems (5 items), symptoms on waking in the morning (4 items), and practical problems (3 items). An overall score was calculated from the individual item scores. All items are weighted equally. A mean score is calculated across all items within each domain. The overall score is the mean across all items and ranges from 0 (not troubled) to 6 (extremely troubled). Higher scores reflect a lower quality of life. Change from Baseline was calculated as the 2-week average minus the Baseline value.
Time Frame	Baseline and Visit 3 (Study Day 14 +/- 2 days)/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	FPNS 200 μg	Cetirizine 10 mg	FPNS Matching Placebo	Cetirizine Matching Placebo
Arm/Group Description	Participants self-administered FPNS 200 µg per day as two sprays in each nostril (50 μg per spray) once daily in the AM for 2 weeks.	Participants self-administered a 10 mg cetrizine capsule once daily in the AM for 2 weeks.	Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.	Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.
Measure Participants	170	170	171	171
Mean (Standard Error) [Scores on a scale]	-1.0 (0.10)	-0.6 (0.09)	-0.8 (0.10)	-0.5 (0.08)

4. Secondary Outcome

Title	Mean Change From Baseline in the AM Pre-dose Instantaneous Total Nasal Symptom Score (iTNSS) Over the Entire Treatment Period
Description	The iTNSS score is the sum of the four individual symptom scores for rhinorrhea, nasal congestion, nasal itching, and sneezing. Each symptom is scored on a scale ranging from 0 to 3; the iTNSS ranges from 0 (none) to 12 (severe). The symptoms were evaluated using a scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The instantaneous assessment of the TNSS scores the four nasal symptoms at the time of the assessment, or at that "instant." The participants themselves scored nasal symptoms in an e-diary once each morning prior to administering study drug. Baseline is defined as the arithmetic average of the iTNSS recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days.
Time Frame	Baseline through the entire treatment period (2 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population. Change from Baseline was analyzed for only those participants who were available for assessment at Baseline and at Weeks 1 and 2. Change from Baseline was calculated as the 2-week average minus the Baseline value.

Arm/Group Title	FPNS 200 μg	Cetirizine 10 mg	FPNS Matching Placebo	Cetirizine Matching Placebo
Arm/Group Description	Participants self-administered FPNS 200 µg per day as two sprays in each nostril (50 μg per spray) once daily in the AM for 2 weeks.	Participants self-administered a 10 mg cetrizine capsule once daily in the AM for 2 weeks.	Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.	Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.
Measure Participants	169	169	171	171
Mean (Standard Error) [Scores on a scale]	-1.9 (0.18)	-1.3 (0.17)	-1.2 (0.18)	-0.6 (0.15)

5. Secondary Outcome

Title	Mean Change From Baseline in the AM Pre-dose Reflective Total Ocular Symptom Score (rTOSS) Over the Entire Treatment Period
Description	The rTOSS is an eye assessment that comprises the sum of the three symptom scores for tearing/watering, itching/burning, and eye redness. Each symptom is scored on a scale of 0 to 3: 0, none; 1, mild; 2, moderate; 3, severe. The rTOSS ranges from 0 (none) to 9 (severe). The reflective assessment scores the participants' ocular symptoms over the preceding 24 hours. The participants themselves scored ocular symptoms in an e-diary. Baseline arithmetic is defined as the average of the rTNSS recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days. Change from Baseline was thus calculated as the 2-week average minus the Baseline value.
Time Frame	Baseline through the entire treatment period (2 weeks)

Outcome Measure Data

Analysis Population Description

Ocular Population: all ITT participants with a Baseline rTOSS of 4 or greater

Arm/Group Title	FPNS 200 μg	Cetirizine 10 mg	FPNS Matching Placebo	Cetirizine Matching Placebo
Arm/Group Description	Participants self-administered FPNS 200 µg per day as two sprays in each nostril (50 μg per spray) once daily in the AM for 2 weeks.	Participants self-administered a 10 mg cetrizine capsule once daily in the AM for 2 weeks.	Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.	Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.
Measure Participants	150	137	152	146
Mean (Standard Error) [Scores on a scale]	-1.6 (0.16)	-1.4 (0.16)	-1.2 (0.16)	-0.8 (0.14)

6. Secondary Outcome

Title	Mean Change From Baseline in the AM Pre-dose Instantaneous Total Ocular Symptom Score (iTOSS) Over the Entire Treatment Period
Description	The iTOSS is an eye assessment that comprises the sum of the three symptom scores for tearing/watering, itching/burning, and eye redness. Each symptom is scored on a scale of 0 to 3: 0, none; 1, mild; 2, moderate; 3, severe. The iTOSS ranges from 0 (none) to 9 (severe). The instantaneous assessment scores the participants' ocular symptoms at the time of the assessment, or at that "instant." The participants themselves scored ocular symptoms in an e-diary once each morning prior to administering study drug. Baseline is defined as the arithmetic average of the iTOSS recorded on the morning of randomization and on each of the six preceding days. A participant may have had as few as 4 days' worth of data contributing to the Baseline average. The 2-week symptom score was defined as the average of the values recorded on the day after randomization and the following 13 days. Change from Baseline was thus calculated as the 2-week average minus the Baseline value.
Time Frame	Baseline through the entire treatment period (2 weeks)

Outcome Measure Data

Analysis Population Description

Ocular Population

Arm/Group Title	FPNS 200 μg	Cetirizine 10 mg	FPNS Matching Placebo	Cetirizine Matching Placebo
Arm/Group Description	Participants self-administered FPNS 200 µg per day as two sprays in each nostril (50 μg per spray) once daily in the AM for 2 weeks.	Participants self-administered a 10 mg cetrizine capsule once daily in the AM for 2 weeks.	Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.	Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.
Measure Participants	150	137	152	146
Mean (Standard Error) [Scores on a scale]	-1.3 (0.15)	-1.1 (0.14)	-1.1 (0.16)	-0.5 (0.13)

7. Secondary Outcome

Title	Mean Change From Baseline in the Combined Nasal and Ocular Reflective Total Symptom Score (rTSS = rTNSS+rTOSS) Over the Entire Treatment Period
Description	The rTSS is the sum of the rTNSS and the rTOSS. The rTNSS score is the sum of the four individual symptom scores for rhinorrhea, nasal congestion, nasal itching, and sneezing. Each symptom is scored on a scale ranging from 0 to 3; the rTNSS ranges from 0 (none) to 12 (severe). Each individual symptom was evaluated using a scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The rTOSS assessment is comprised of the sum of the three symptom scores for tearing/watering, itching/burning, and eye redness. Each symptom is scored on a scale of 0 to 3: 0, none; 1, mild; 2, moderate; or 3, severe. The rTOSS ranges from 0 (none) to 9 (severe). The reflective assessment scores participants' symptoms over the previous 24 hours. The participants themselves scored nasal and ocular symptoms in an e-diary. Baseline is defined as the arithmetic average of the rTSS recorded on the morning of randomization and on each of the six preceding days.
Time Frame	Baseline through the entire treatment period (2 weeks)

Outcome Measure Data

Analysis Population Description

Ocular Population. Change from Baseline was calculated as the 2-week average minus the Baseline value.n

Arm/Group Title	FPNS 200 μg	Cetirizine 10 mg	FPNS Matching Placebo	Cetirizine Matching Placebo
Arm/Group Description	Participants self-administered FPNS 200 µg per day as two sprays in each nostril (50 μg per spray) once daily in the AM for 2 weeks.	Participants self-administered a 10 mg cetrizine capsule once daily in the AM for 2 weeks.	Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.	Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.
Measure Participants	150	137	152	146
Mean (Standard Error) [Scores on a scale]	-3.9 (0.34)	-3.4 (0.34)	-2.7 (0.34)	-1.7 (0.30)

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment until the End-of-Study visit (up to Day 14).
Adverse Event Reporting Description	SAEs and non-serious AEs are reported for the Intent-to-Treat Population, comprised of all participants who were randomized and received at least one dose of study medication.
Arm/Group Title	FPNS 200 μg		Cetirizine 10 mg		FPNS Matching Placebo		Cetirizine Matching Placebo
Arm/Group Description	Participants self-administered FPNS 200 µg per day as two sprays in each nostril (50 μg per spray) once daily in the AM for 2 weeks.		Participants self-administered a 10 mg cetrizine capsule once daily in the AM for 2 weeks.		Participants self-administered matching placebo to FPNS as two sprays in each nostril (50 µg per spray) once daily in the AM for 2 weeks.		Participants self-administered matching placebo to cetrizine capsule once daily in the AM for 2 weeks.
All Cause Mortality
	FPNS 200 μg		Cetirizine 10 mg		FPNS Matching Placebo		Cetirizine Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	FPNS 200 μg		Cetirizine 10 mg		FPNS Matching Placebo		Cetirizine Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/170 (0%)		0/170 (0%)		0/171 (0%)		0/171 (0%)
Other (Not Including Serious) Adverse Events
	FPNS 200 μg		Cetirizine 10 mg		FPNS Matching Placebo		Cetirizine Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/170 (5.9%)		13/170 (7.6%)		10/171 (5.8%)		10/171 (5.8%)
Ear and labyrinth disorders
Ear pain	0/170 (0%)		1/170 (0.6%)		1/171 (0.6%)		0/171 (0%)
Eye disorders
Conjunctivitis	0/170 (0%)		0/170 (0%)		0/171 (0%)		1/171 (0.6%)
Conjunctivitis allergic	0/170 (0%)		0/170 (0%)		0/171 (0%)		1/171 (0.6%)
Gastrointestinal disorders
Dry mouth	0/170 (0%)		0/170 (0%)		1/171 (0.6%)		0/171 (0%)
Dyspepsia	0/170 (0%)		1/170 (0.6%)		0/171 (0%)		0/171 (0%)
Dysphagia	0/170 (0%)		0/170 (0%)		0/171 (0%)		1/171 (0.6%)
Toothache	0/170 (0%)		1/170 (0.6%)		0/171 (0%)		0/171 (0%)
General disorders
Fatigue	1/170 (0.6%)		1/170 (0.6%)		0/171 (0%)		0/171 (0%)
Infections and infestations
Fungal infection	1/170 (0.6%)		0/170 (0%)		0/171 (0%)		1/171 (0.6%)
Gastroenteritis viral	1/170 (0.6%)		0/170 (0%)		1/171 (0.6%)		0/171 (0%)
Sinusitis	0/170 (0%)		0/170 (0%)		1/171 (0.6%)		1/171 (0.6%)
Upper respiratory tract infection	2/170 (1.2%)		0/170 (0%)		0/171 (0%)		0/171 (0%)
Viral upper respiratory tract infection	2/170 (1.2%)		0/170 (0%)		0/171 (0%)		0/171 (0%)
Ear infection	0/170 (0%)		0/170 (0%)		1/171 (0.6%)		0/171 (0%)
Gastroenteritis	0/170 (0%)		0/170 (0%)		0/171 (0%)		1/171 (0.6%)
Nasopharyngitis	0/170 (0%)		1/170 (0.6%)		0/171 (0%)		0/171 (0%)
Oral herpes	0/170 (0%)		0/170 (0%)		1/171 (0.6%)		0/171 (0%)
Injury, poisoning and procedural complications
Arthropod bite	0/170 (0%)		0/170 (0%)		0/171 (0%)		1/171 (0.6%)
Tooth fracture	0/170 (0%)		0/170 (0%)		1/171 (0.6%)		0/171 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/170 (0%)		2/170 (1.2%)		0/171 (0%)		0/171 (0%)
Arthralgia	1/170 (0.6%)		0/170 (0%)		0/171 (0%)		0/171 (0%)
Myalgia	0/170 (0%)		1/170 (0.6%)		0/171 (0%)		0/171 (0%)
Pain in extremity	0/170 (0%)		1/170 (0.6%)		0/171 (0%)		0/171 (0%)
Nervous system disorders
Headache	2/170 (1.2%)		3/170 (1.8%)		2/171 (1.2%)		3/171 (1.8%)
Sinus headache	0/170 (0%)		1/170 (0.6%)		0/171 (0%)		0/171 (0%)
Somnolence	0/170 (0%)		1/170 (0.6%)		0/171 (0%)		0/171 (0%)
Psychiatric disorders
Depression	1/170 (0.6%)		0/170 (0%)		0/171 (0%)		0/171 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/170 (0%)		1/170 (0.6%)		1/171 (0.6%)		0/171 (0%)
Nasal dryness	0/170 (0%)		1/170 (0.6%)		1/171 (0.6%)		0/171 (0%)
Oropharyngeal pain	1/170 (0.6%)		1/170 (0.6%)		0/171 (0%)		0/171 (0%)
Dry throat	0/170 (0%)		0/170 (0%)		1/171 (0.6%)		0/171 (0%)
Respiratory disorder	0/170 (0%)		0/170 (0%)		1/171 (0.6%)		0/171 (0%)
Sneezing	0/170 (0%)		0/170 (0%)		1/171 (0.6%)		0/171 (0%)
Throat irritation	0/170 (0%)		0/170 (0%)		1/171 (0.6%)		0/171 (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.