A Clinical Study With Fluticasone Furoate Nasal Spray And Vehicle Placebo For The Treatment Of Perennial (Year-round) Allergic Rhinitis

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00682643
• Collaborator: (none)
• Enrollment: 550
• Locations: 56
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to assess long-term ocular safety of fluticasone furoate nasal spray in adult and adolescent subjects diagnosed with perennial allergic rhinitis.

Condition or Disease	Intervention/Treatment	Phase
Rhinitis, Allergic, Perennial	Drug: fluticasone furoate nasal spray; Drug: vehicle placebo nasal spray	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 550 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter, Two-Year Study to Evaluate the Ocular Safety of Once-Daily, Fluticasone Furoate Nasal Spray 110mcg in Adults and Adolescents 12 Years of Age and Older With Perennial Allergic Rhinitis
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: vehicle placebo nasal spray	Drug: vehicle placebo nasal spray; placebo
Active Comparator: fluticasone furoate nasal spray	Drug: fluticasone furoate nasal spray; fluticasone furoate nasal spray

Outcome Measures

Primary Outcome Measures

1. Cumulative Proportion (CU) of Participants (Par.) With an Event, as Measured as a Percentage, for Posterior Subcapsular Opacity (P) [Baseline; Weeks 12, 24, 36, 52, 64, 76, 88, and 104]

   An event for P (opacity in the lens positioned just anterior to the posterior lens capsule and characterized by the posterior migration of lens epithelial cells from the lens bow) is defined as an increase of >=0.3 from baseline in Lens Opacities Classification System, Version III (LOCS III; system used for the grading and comparison of cataract severity and type based on standard color photographic transparencies) grade for P (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Data represent the Kaplan-Meier estimate for the CU of par. with an event of P based on a lifetest table.

2. Cumulative Proportion of Participants, as Measured as a Percentage, With an Intraocular Pressure (IOP) Event [Baseline; Weeks 12, 24, 36, 52, 64, 76, 88, and 104]

   An event for IOP is defined as an increase of 7 millimeters of mercury (mm Hg) or greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry (GAT). GAT is a commonly used method of determining approximate intraocular pressure. The data below represent the Kaplan-Meier estimate for the cumulative proportion of participants with an IOP event based on a lifetest table.

Secondary Outcome Measures

1. Change From Baseline in LOCS III Posterior Subcapsular Opacity at Week 52 and Week 104 [Baseline, Week 52, and Week 104]

   An event for P (opacity in the lens positioned just anterior to the posterior lens capsule and characterized by the posterior migration of lens epithelial cells from the lens bow) is defined as an increase of >=0.3 from baseline in LOCS III (system used for the grading and comparison of cataract severity and type based on standard color photographic transparencies) grade for P (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Change from baseline was calculated by subtracting the baseline value from the Week 52 and Week 104 value.

2. Number of Participants With the Indicated Change From Baseline in LOCS III Posterior Subcapsular Opacity by Increments of 0.1 at Weeks 52 and 104 [Baseline, Week 52, and Week 104]

   An event for P is defined as an increase of >=0.3 from baseline in LOCS III (classification system based on standard color photographic transparencies) grade for P (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Change from baseline was calculated by subtracting the baseline value from the Week 52 and Week 104 value.

3. Change From Baseline in LOCS III Cortical Opacity (C) at Week 52 and Week 104 [Baseline, Week 52, and Week 104]

   An event for C (an opacity starting at the outer edge of the lens and progressing toward the center) is defined as an increase of >=0.3 from baseline in LOCS III (system used for the grading and comparison of cataract severity and type based on standard color photographic transparencies) grade for C (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Change from baseline was calculated by subtracting the baseline value from the Week 52 and Week 104 value.

4. Number of Participants With the Indicated Change From Baseline in Cortical Opacity by Increment Categories of >=0.3, >=0.5, and >=1.0 at Weeks 52 and 104 [Baseline, Week 52, and Week 104]

   An event for C (an opacity starting at the outer edge of the lens and progressing toward the center) is defined as an increase of >=0.3 from baseline in LOCS III (system used for the grading and comparison of cataract severity and type based on standard color photographic transparencies) grade for C (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Change from baseline was calculated by subtracting the baseline value from the Week 52 and Week 104 value.

5. Change From Baseline in LOCS III Nuclear Opacity (NO) at Week 52 and Week 104 [Baseline, Week 52, and Week 104]

   Nuclear opacity refers to the opacity in the central nucleus of the eye.The range for NO is 0.1 (no opacity) to 6.9 (maximum opacity). Change from baseline in NO was calculated by subtracting the baseline value from the Week 52 or Week 104 value.

6. Change From Baseline in Nuclear Color (NC) at Week 52 and Week 104 [Baseline, Week 52, and Week 104]

   Nuclear color is associated with the force required to compress a lens to 75% of its original depth. The range for NC is 0.1 (no opacity) to 6.9 (maximum opacity). Change from baseline in NC was calculated by subtracting the baseline value from the Week 52 or Week 104 value.

7. Change From Baseline in Intraocular Pressure (IOP) at Weeks 52 and 104 [Baseline, Week 52, and Week 104]

   An event for IOP is defined as an increase of 7 mm Hg or greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry. Participants without post-baseline ophthalmic exam data were censored at the randomization date. Change from baseline was calculated by subtracting the baseline value from the Week 52 or Week 104 value.

8. Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) by Increments of 1 mm Hg at Week 52 [Baseline and Week 52]

   An event for IOP is defined as an increase of 7 mm Hg or greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry. Participants without post-baseline ophthalmic exam data were censored at the randomization date. Change from baseline was calculated by subtracting the baseline value from the Week 52 value.

9. Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) by Increments of 1 mm Hg at Week 104 [Baseline and Week 104]

   An event for IOP is defined as an increase of 7 mm Hg or greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry. Participants without post-baseline ophthalmic exam data were censored at the randomization date. Change from baseline in IOP was calculated by subtracting the baseline value from the Week 104 value.

10. Change From Baseline in Logarithm of the Minimum Angle of Resolution (LogMAR) Visual Acuity (VA) Using Early Treatment Diabetic Retinopathy Study (ETDRS) Charts at Week 52 and Week 104 [Baseline, Week 52, and Week 104]

    ETDRS charts are used to measure VA (the ability to resolve fine image details). Participants must have had a best-corrected distance VA of =< 0.18 on the LogMAR scale using ETDRS charts in both eyes measured separately. The LogMAR scale (expressed as the [decadic] logarithm of the minimum angle of resolution [range from +1.00 to -0.30]) converts the geometric sequence of a traditional chart to a linear scale. It measures VA loss; positive values indicate vision loss, whereas negative values denote normal or better VA. A lower LogMAR value indicates better VA.

11. Percent Change From Baseline in the Funduscopic Horizontal Cup-to-disc Ratio at Week 104 [Baseline and Week 104]

    The funduscopic horizontal cup-to-risk ratio assesses the progression of glaucoma. Percent change from baseline in funduscopic horizontal cup-to-disc ratio at Week 104 was calculated by substracting the baseline value from the Week 104 value (both expressed as a percent). The cup-to-disc ratio compares the diameter of the "cup" portion of the optic disc with the total diameter of the optic disc. A large cup-to-disc ratio may imply glaucoma or other pathology.

12. Change From Baseline in the Daily Reflective Total Nasal Symptom Score (rTNSS) for the Indicated Study Periods [Baseline, Weeks 1 to 26, Weeks 27 to 52, Weeks 53 to 78, and Weeks 79 to 104]

    rTNSS was evaluated on a 4-point categorical scale (sum of the scores for rhinorrhea, nasal congestion, nasal itching, and sneezing; range=0-12). The data collected were used as a measure for treatment compliance. The scores on the scale were based on the severity of each nasal symptom: 0=none (symptom is not present); 1=mild (sign/symptom is clearly present but minimal awareness; easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable); 3=severe (sign/symptom is hard to tolerate; causes interference with activities of daily living and/or sleeping).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Subjects eligible for enrollment in the study must meet all of the following criteria:

• Informed consent

• Subject has provided an appropriately signed and dated informed consent. An appropriately signed and dated assent must be obtained from the parents or guardian if the subject is a child under 18 years of age.

• Outpatient

• Subject is treatable on an outpatient basis.

• Age

• 12 years of age and older at Visit 2

• Male or eligible female Female subjects should not be enrolled if they plan to become pregnant during the time of study participation.

To be eligible for entry into the study, females of childbearing potential must commit to the consistent and correct use of an acceptable method of birth control, as defined by the following:

• Abstinence Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days).

• Oral contraceptive (either combined estrogen/progestin or progestin only)

• Injectable progestogen

• Implants of levonorgestrel

• Percutaneous contraceptive patches

• Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year,

• Male partner who is sterile (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study and is the sole sexual partner for that female subject, or

• Double barrier method-condom or occlusive cap (diaphragm or cervical /vault caps) plus Spermicide,

• Estrogenic vaginal ring. A urine pregnancy test will be done at the screening visit to confirm females of childbearing potential are not pregnant upon entry into the study. In addition, urine pregnancy tests will be done for all females of childbearing potential at each clinic visit.

• Diagnosis of PAR to include:

A positive skin test (by prick method) response to appropriate perennial allergen (house dust mites, animal dander, mold, or cockroach) within last 12 months prior to Visit 1 or at Visit 1.

A positive skin test is defined as a wheal ³3mm larger than the diluent control for prick testing.

•Two year medical history and past treatment of PAR (written or verbal confirmation) which includes perennial, i.e., year-round, symptoms. PAR symptoms could include nasal congestion, rhinorrhea, nasal itching and sneezing.

In vitro tests for specific IgE (such as RAST, PRIST) will not be allowed for the diagnosis of PAR.

NOTE: Subjects who meet the above criteria and who also may have seasonal allergic rhinitis (SAR) and/or perennial non-allergic rhinitis (PNAR) are eligible for randomization.

• Environment

•Subject must be symptomatic to appropriate perennial allergen (animal dander, house dust mites, cockroach, mold) and willing to maintain, as much as possible, the same environment throughout the study.

• Ability to comply with study procedures Subject understands and is willing, able and likely to comply with study procedures and restrictions.

• Literate Subject must be able to read, comprehend, and record information in English

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

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

• A historical or current evidence of clinically significant uncontrolled disease of any body system (e.g., tuberculosis, psychological disorders, eczema). 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.

• History or current diagnosis of diabetes mellitus

• Uncontrolled hypertension (i.e., systolic blood pressure ³ 140mm Hg or diastolic blood pressure ³ 90mm Hg)

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

• Nasal (e.g., nasal septum) or ocular injury/surgery in the last 6 months (including LASIK eye surgery)

• Asthma, with the exception of mild intermittent asthma [National Asthma Education and Prevention Program (NAEPP) Guidelines for the Diagnosis and Management of Asthma - Expert Panel Report 3, National Institutes of Health, August 28, 2007.

NOTE: Subjects will be allowed to use short-acting inhaled beta2 agonists ONLY on an as needed basis.

• 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 ocular herpes simplex

• Current cataract and/or previous history of cataract surgery

• Physical impairment that would affect subject's ability to participate safely and fully 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

• History of Hepatitis B or C

• Use of corticosteroids, defined as:

• Intranasal corticosteroid within 4 weeks prior to Visit 1 (e.g., VERAMYST, FLONASE™, Nasonex, Rhinocort).

• Inhaled, oral, intramuscular, intravenous, ocular, and/or topical corticosteroids (with the exception of topical hydrocortisone, 1% or less, or equivalent) within 8 weeks prior to Visit 1.

• Use of other allergy medications within the timeframe indicated relative to Visit 1

• Intranasal or ocular cromolyn within 14 days prior to Visit 1 (e.g., Nasalcrom, Crolom)

• Short-acting prescription and non-prescription antihistamines, including ocular preparations and antihistamines contained in insomnia and "night time" pain formulations, within 3 days prior to Visit 1 (e.g., Benadryl, Chlortrimeton, Dimetane, Tavist)

• Long-acting antihistamines within 10 days prior to Visit 1 (e.g., Allegra, Claritin, Clarinex, Zyrtec).

• Intranasal antihistamines (e.g., Astelin) within 2 weeks prior to Visit 1

• Oral or intranasal decongestants within 3 days prior to Visit 1 (e.g., Sudafed)

• Long-acting beta-agonists within 3 days prior to Visit 1 (e.g., SEREVENT™, Foradil)

• Intranasal, oral, or inhaled anticholinergics within 3 days prior to Visit 1 (e.g., Atrovent)

• Oral antileukotrienes within 3 days of Visit 1 (e.g., Singulair)

• Subcutaneous omalizumab (Xolair) within 5 months of Visit 1

• Use of other medications that may affect allergic rhinitis or its symptoms

• Chronic use of concomitant medications, such as tricyclic antidepressants, that would affect assessment of the effectiveness of the study drug

• Use of other intranasally administered medications (e.g., Miacalcin)

• Use of immunosuppressive medications 8 weeks prior to screening and during the study

• Immunotherapy Immunotherapy patients may be enrolled in the study if the immunotherapy was not initiated within 30 days of Visit 1, 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.

• Use of any medications that significantly alter the pharmacokinetics of fluticasone furoate (ritonavir and ketoconazole)

• Use of chronic treatment with agents known to promote the development of cataracts (e.g., potassium-sparing diuretics and allopurinol)

• Allergy/Intolerance

• Known hypersensitivity to corticosteroids or any excipients

• Clinical trial/experimental medication experience

• Has recent exposure to an investigational study drug within 30 days of Visit 1

• Participation in a previous or current FFNS (GW685698X) clinical study

• Positive urine pregnancy test or female who is breastfeeding

• Has a positive or inconclusive pregnancy test at Visit 1 or Visit 2

• Affiliation with investigational site

• Subject is a participating investigator, sub-investigator, study co-ordinator, or employee of a participating investigator, or is an immediate family member of the aforementioned.

• Tobacco use

• Subject currently uses smoking products including cigarettes, cigars, and pipe or chewing tobacco, or has used these products in the last 6 months

• Chickenpox or measles A subject is not eligible if he/she currently has chickenpox or measles, or has been exposed to chickenpox or measles during the last three weeks and is non-immune. If a subject develops chickenpox or measles during the study, he/she will be withdrawn from the study. If a non-immune subject is exposed to chickenpox or measles during the study, his/her continuation in the study will be at the discretion of the investigator, taking into consideration the likelihood of developing active disease.

• Findings of a clinically significant, abnormal ECG

• Findings of a clinically significant laboratory abnormality

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Oxford	Alabama	United States	36203
2	GSK Investigational Site	Little Rock	Arkansas	United States	72205
3	GSK Investigational Site	Fresno	California	United States	93720
4	GSK Investigational Site	Huntington Beach	California	United States	92647
5	GSK Investigational Site	Los Angeles	California	United States	90025
6	GSK Investigational Site	Mission Viejo	California	United States	92691
7	GSK Investigational Site	Rolling Hills Estates	California	United States	90274
8	GSK Investigational Site	Roseville	California	United States	95678
9	GSK Investigational Site	Sacramento	California	United States	95823
10	GSK Investigational Site	San Diego	California	United States	92120
11	GSK Investigational Site	San Diego	California	United States	92123
12	GSK Investigational Site	San Jose	California	United States	95117
13	GSK Investigational Site	Stockton	California	United States	95207
14	GSK Investigational Site	Vista	California	United States	92083
15	GSK Investigational Site	Walnut Creek	California	United States	94598
16	GSK Investigational Site	Colorado Springs	Colorado	United States	80907
17	GSK Investigational Site	Denver	Colorado	United States	80230
18	GSK Investigational Site	Englewood	Colorado	United States	80112
19	GSK Investigational Site	Wheat Ridge	Colorado	United States	80033
20	GSK Investigational Site	Tallahassee	Florida	United States	32308
21	GSK Investigational Site	Conyers	Georgia	United States	30013
22	GSK Investigational Site	Gainesville	Georgia	United States	30501
23	GSK Investigational Site	Lawrenceville	Georgia	United States	30045
24	GSK Investigational Site	Stockbridge	Georgia	United States	30281
25	GSK Investigational Site	Indianapolis	Indiana	United States	46208
26	GSK Investigational Site	South Bend	Indiana	United States	46617
27	GSK Investigational Site	Bethesda	Maryland	United States	20814
28	GSK Investigational Site	North Dartmouth	Massachusetts	United States	02747
29	GSK Investigational Site	Minneapolis	Minnesota	United States	55402
30	GSK Investigational Site	St. Louis	Missouri	United States	63141
31	GSK Investigational Site	Bozeman	Montana	United States	59718
32	GSK Investigational Site	Bellevue	Nebraska	United States	68123-4303
33	GSK Investigational Site	Omaha	Nebraska	United States	68130
34	GSK Investigational Site	Omaha	Nebraska	United States	68131
35	GSK Investigational Site	Ocean	New Jersey	United States	07712
36	GSK Investigational Site	Skillman	New Jersey	United States	08558
37	GSK Investigational Site	Asheville	North Carolina	United States	28801
38	GSK Investigational Site	Raleigh	North Carolina	United States	27607
39	GSK Investigational Site	Canton	Ohio	United States	44718
40	GSK Investigational Site	Cincinnati	Ohio	United States	45231
41	GSK Investigational Site	Sylvania	Ohio	United States	43560
42	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73104
43	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73120
44	GSK Investigational Site	Eugene	Oregon	United States	97401
45	GSK Investigational Site	Portland	Oregon	United States	97213
46	GSK Investigational Site	Summerville	South Carolina	United States	29485
47	GSK Investigational Site	Austin	Texas	United States	78750
48	GSK Investigational Site	Dallas	Texas	United States	75230
49	GSK Investigational Site	Dallas	Texas	United States	75231-4307
50	GSK Investigational Site	El Paso	Texas	United States	79903
51	GSK Investigational Site	Kerrville	Texas	United States	78028
52	GSK Investigational Site	San Antonio	Texas	United States	78229
53	GSK Investigational Site	Waco	Texas	United States	76712
54	GSK Investigational Site	South Burlington	Vermont	United States	05403
55	GSK Investigational Site	Spokane	Washington	United States	99204
56	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

• LaForce C, Journeay GE, Miller SD, Silvey MJ, Wu W, Lee LA, Chylack LT Jr. Ocular safety of fluticasone furoate nasal spray in patients with perennial allergic rhinitis: a 2-year study. Ann Allergy Asthma Immunol. 2013 Jul;111(1):45-50. doi: 10.1016/j.anai.2013.04.013. Epub 2013 May 12.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00682643
• Other Study ID Numbers: FFR110537
• First Posted: May 22, 2008
• Last Update Posted: Jan 13, 2017
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Perennial Allergic Rhinitis; fluticasone furoate; ocular safety
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Fluticasone; Xhance

Study Results

Participant Flow

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Period Title: Overall Study
STARTED	182	368
COMPLETED	104	199
NOT COMPLETED	78	169

Baseline Characteristics

Arm/Group Title	Placebo	FF 110 mcg QD	Total
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.	Total of all reporting groups
Overall Participants	181	367	548
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.0 (13.34)	37.0 (13.48)	37.4 (13.43)
Gender (Count of Participants)
Female	116 64.1%	255 69.5%	371 67.7%
Male	65 35.9%	112 30.5%	177 32.3%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage	29 16%	50 13.6%	79 14.4%
American Indian or Alaska Native	1 0.6%	4 1.1%	5 0.9%
Central/South Asian Heritage	0 0%	1 0.3%	1 0.2%
Japanese/East Asian/South East Asian Heritage	2 1.1%	6 1.6%	8 1.5%
Mixed Asian Heritage	0 0%	1 0.3%	1 0.2%
Native Hawaiian or other Pacific Islander	2 1.1%	2 0.5%	4 0.7%
White	146 80.7%	303 82.6%	449 81.9%
African American/African Heritage & White	1 0.6%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Cumulative Proportion (CU) of Participants (Par.) With an Event, as Measured as a Percentage, for Posterior Subcapsular Opacity (P)
Description	An event for P (opacity in the lens positioned just anterior to the posterior lens capsule and characterized by the posterior migration of lens epithelial cells from the lens bow) is defined as an increase of >=0.3 from baseline in Lens Opacities Classification System, Version III (LOCS III; system used for the grading and comparison of cataract severity and type based on standard color photographic transparencies) grade for P (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Data represent the Kaplan-Meier estimate for the CU of par. with an event of P based on a lifetest table.
Time Frame	Baseline; Weeks 12, 24, 36, 52, 64, 76, 88, and 104

Outcome Measure Data

Analysis Population Description

ITT Population. All participants (par.) with post-baseline ophthalmic examination data were included in the analysis for this endpoint. Par. without post-baseline ophthalmic exam data were censored at the randomization data. Par. who completed the study without an event for P or were discontinued for reasons other than an event for P were censored.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	168	344
Week 12	0.60 0.3%	0.88 0.2%
Week 24	1.24 0.7%	1.84 0.5%
Week 36	1.93 1.1%	2.56 0.7%
Week 52	2.68 1.5%	3.72 1%
Week 64	2.68 1.5%	3.72 1%
Week 76	2.68 1.5%	3.72 1%
Week 88	2.68 1.5%	4.59 1.3%
Week 104	2.68 1.5%	5.09 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF 110 mcg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.395
	Comments	Wald Chi-Square test based on a proportional hazards model adjusting for age and baseline value
	Method	Wald Chi-square
	Comments

2. Primary Outcome

Title	Cumulative Proportion of Participants, as Measured as a Percentage, With an Intraocular Pressure (IOP) Event
Description	An event for IOP is defined as an increase of 7 millimeters of mercury (mm Hg) or greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry (GAT). GAT is a commonly used method of determining approximate intraocular pressure. The data below represent the Kaplan-Meier estimate for the cumulative proportion of participants with an IOP event based on a lifetest table.
Time Frame	Baseline; Weeks 12, 24, 36, 52, 64, 76, 88, and 104

Outcome Measure Data

Analysis Population Description

ITT Population. All participants with post-baseline ophthalmic examination data were included in the analysis for this endpoint.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	168	344
Week 12	0.00 0%	0.00 0%
Week 24	0.00 0%	0.32 0.1%
Week 36	0.00 0%	0.32 0.1%
Week 52	0.00 0%	0.71 0.2%
Week 64	0.00 0%	1.12 0.3%
Week 76	0.00 0%	1.98 0.5%
Week 88	0.84 0.5%	1.98 0.5%
Week 104	0.84 0.5%	2.96 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF 110 mcg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.342
	Comments	Wald Chi-Square test based on a proportional hazards model adjusting for age and baseline value
	Method	Wald Chi-square
	Comments

3. Secondary Outcome

Title	Change From Baseline in LOCS III Posterior Subcapsular Opacity at Week 52 and Week 104
Description	An event for P (opacity in the lens positioned just anterior to the posterior lens capsule and characterized by the posterior migration of lens epithelial cells from the lens bow) is defined as an increase of >=0.3 from baseline in LOCS III (system used for the grading and comparison of cataract severity and type based on standard color photographic transparencies) grade for P (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Change from baseline was calculated by subtracting the baseline value from the Week 52 and Week 104 value.
Time Frame	Baseline, Week 52, and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	130	198
Left eye, Week 52; n=130, 251	0.00 (0.042)	0.00 (0.063)
Left eye, Week 104; n=104, 198	0.00 (0.039)	0.00 (0.083)
Right eye, Week 52; n=130, 251	0.00 (0.057)	0.00 (0.061)
Right eye, Week 104; n=104, 198	0.00 (0.042)	-0.01 (0.068)

4. Secondary Outcome

Title	Number of Participants With the Indicated Change From Baseline in LOCS III Posterior Subcapsular Opacity by Increments of 0.1 at Weeks 52 and 104
Description	An event for P is defined as an increase of >=0.3 from baseline in LOCS III (classification system based on standard color photographic transparencies) grade for P (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Change from baseline was calculated by subtracting the baseline value from the Week 52 and Week 104 value.
Time Frame	Baseline, Week 52, and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	130	251
Left eye, Week 52, <-0.3; n=130, 251	0 0%	0 0%
Left eye, Week 52, -0.3; n=130, 251	0 0%	0 0%
Left eye, Week 52, -0.2; n=130, 251	2 1.1%	5 1.4%
Left eye, Week 52, -0.1; n=130, 251	3 1.7%	13 3.5%
Left eye, Week 52, 0; n=130, 251	121 66.9%	218 59.4%
Left eye, Week 52, 0.1; n=130, 251	3 1.7%	12 3.3%
Left eye, Week 52, 0.2; n=130, 251	0 0%	0 0%
Left eye, Week 52, 0.3; n=130, 251	1 0.6%	2 0.5%
Left eye, Week 52, 0.4; n=130, 251	0 0%	0 0%
Left eye, Week 52, 0.5; n=130, 251	0 0%	0 0%
Left eye, Week 52, 0.6; n=130, 251	0 0%	1 0.3%
Left eye, Week 52, 0.7; n=130, 251	0 0%	0 0%
Left eye, Week 52, 0.8; n=130, 251	0 0%	0 0%
Left eye, Week 52, >=0.9; n=130, 251	0 0%	0 0%
Left eye, Week 52, >=0.3; n=130, 251	1 0.6%	3 0.8%
Left eye, Week 52, >=0.5; n=130, 251	0 0%	1 0.3%
Left eye, Week 52, >=1.0; n=130, 251	0 0%	0 0%
Right eye, Week 52, <-0.3; n=130, 251	0 0%	0 0%
Right eye, Week 52, -0.3; n=130, 251	1 0.6%	0 0%
Right eye, Week 52, -0.2; n=130, 251	1 0.6%	5 1.4%
Right eye, Week 52, -0.1; n=130, 251	0 0%	10 2.7%
Right eye, Week 52, 0; n=130, 251	122 67.4%	218 59.4%
Right eye, Week 52, 0.1; n=130, 251	4 2.2%	13 3.5%
Right eye, Week 52, 0.2; n=130, 251	0 0%	2 0.5%
Right eye, Week 52, 0.3; n=130, 251	1 0.6%	1 0.3%
Right eye, Week 52, 0.4; n=130, 251	1 0.6%	2 0.5%
Right eye, Week 52, 0.5; n=130, 251	0 0%	0 0%
Right eye, Week 52, 0.6; n=130, 251	0 0%	0 0%
Right eye, Week 52, 0.7; n=130, 251	0 0%	0 0%
Right eye, Week 52, 0.8; n=130, 251	0 0%	0 0%
Right eye, Week 52, >=0.9; n=130, 251	0 0%	0 0%
Right eye, Week 52, >=0.3; n=130, 251	2 1.1%	3 0.8%
Right eye, Week 52, >=0.5; n=130, 251	0 0%	0 0%
Right eye, Week 52, >=1.0; n=130, 251	0 0%	0 0%
Left eye, Week 104, <-0.3; n=104, 198	0 0%	0 0%
Left eye, Week 104, -0.3; n=104, 198	0 0%	0 0%
Left eye, Week 104, -0.2; n=104, 198	2 1.1%	5 1.4%
Left eye, Week 104, -0.1; n=104, 198	3 1.7%	11 3%
Left eye, Week 104, 0; n=104, 198	94 51.9%	175 47.7%
Left eye, Week 104, 0.1; n=104, 198	5 2.8%	5 1.4%
Left eye, Week 104, 0.2; n=104, 198	0 0%	0 0%
Left eye, Week 104, 0.3; n=104, 198	0 0%	0 0%
Left eye, Week 104, 0.4; n=104, 198	0 0%	0 0%
Left eye, Week 104, 0.5; n=104, 198	0 0%	0 0%
Left eye, Week 104, 0.6; n=104, 198	0 0%	1 0.3%
Left eye, Week 104, 0.7; n=104, 198	0 0%	0 0%
Left eye, Week 104, 0.8; n=104, 198	0 0%	1 0.3%
Left eye, Week 104, >=0.9; n=104, 198	0 0%	0 0%
Left eye, Week 104, >=0.3; n=104, 198	0 0%	2 0.5%
Left eye, Week 104, >=0.5; n=104, 198	0 0%	2 0.5%
Left eye, Week 104, >=1.0; n=104, 198	0 0%	0 0%
Right eye, Week 104, <-0.3; n=104, 198	0 0%	0 0%
Right eye, Week 104, -0.3; n=104, 198	1 0.6%	0 0%
Right eye, Week 104, -0.2; n=104, 198	1 0.6%	5 1.4%
Right eye, Week 104, -0.1; n=104, 198	2 1.1%	14 3.8%
Right eye, Week 104, 0; n=104, 198	97 53.6%	174 47.4%
Right eye, Week 104, 0.1; n=104, 198	3 1.7%	2 0.5%
Right eye, Week 104, 0.2; n=104, 198	0 0%	2 0.5%
Right eye, Week 104, 0.3; n=104, 198	0 0%	0 0%
Right eye, Week 104, 0.4; n=104, 198	0 0%	0 0%
Right eye, Week 104, 0.5; n=104, 198	0 0%	0 0%
Right eye, Week 104, 0.6; n=104, 198	0 0%	0 0%
Right eye, Week 104, 0.7; n=104, 198	0 0%	1 0.3%
Right eye, Week 104, 0.8; n=104, 198	0 0%	0 0%
Right eye, Week 104, >=0.9; n=104, 198	0 0%	0 0%
Right eye, Week 104, >=0.3; n=104, 198	0 0%	1 0.3%
Right eye, Week 104, >=0.5; n=104, 198	0 0%	1 0.3%
Right eye, Week 104, >=1.0; n=104, 198	0 0%	0 0%

5. Secondary Outcome

Title	Change From Baseline in LOCS III Cortical Opacity (C) at Week 52 and Week 104
Description	An event for C (an opacity starting at the outer edge of the lens and progressing toward the center) is defined as an increase of >=0.3 from baseline in LOCS III (system used for the grading and comparison of cataract severity and type based on standard color photographic transparencies) grade for C (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Change from baseline was calculated by subtracting the baseline value from the Week 52 and Week 104 value.
Time Frame	Baseline, Week 52, and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	130	251
Left eye, Week 52; n=130, 251	0.01 (0.210)	0.00 (0.113)
Left eye, Week 104; n=104, 198	0.02 (0.210)	0.01 (0.186)
Right eye, Week 52; n=130, 251	-0.01 (0.229)	0.00 (0.154)
Right eye, Week 104; n=104, 198	0.02 (0.187)	0.01 (0.186)

6. Secondary Outcome

Title	Number of Participants With the Indicated Change From Baseline in Cortical Opacity by Increment Categories of >=0.3, >=0.5, and >=1.0 at Weeks 52 and 104
Description	An event for C (an opacity starting at the outer edge of the lens and progressing toward the center) is defined as an increase of >=0.3 from baseline in LOCS III (system used for the grading and comparison of cataract severity and type based on standard color photographic transparencies) grade for C (range=0.1 [lens clear] to 5.9 [lens unclear]), in either eye. Change from baseline was calculated by subtracting the baseline value from the Week 52 and Week 104 value.
Time Frame	Baseline, Week 52, and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	130	251
Left eye, Week 52, >=0.3; n=130, 251	4 2.2%	4 1.1%
Left eye, Week 52, >=0.5; n=130, 251	1 0.6%	0 0%
Left eye, Week 52, >=1.0; n=130, 251	1 0.6%	0 0%
Right eye, Week 52, >=0.3; n=130, 251	3 1.7%	8 2.2%
Right eye, Week 52, >=0.5; n=130, 251	1 0.6%	2 0.5%
Right eye, Week 52, >=1.0; n=130, 251	1 0.6%	0 0%
Left eye, Week 104, >=0.3; n=104, 198	6 3.3%	10 2.7%
Left eye, Week 104, >=0.5; n=104, 198	3 1.7%	4 1.1%
Left eye, Week 104, >=1.0; n=104, 198	1 0.6%	1 0.3%
Right eye, Week 104, >=0.3; n=104, 198	3 1.7%	10 2.7%
Right eye, Week 104, >=0.5; n=104, 198	2 1.1%	4 1.1%
Right eye, Week 104, >=1.0; n=104, 198	1 0.6%	2 0.5%

7. Secondary Outcome

Title	Change From Baseline in LOCS III Nuclear Opacity (NO) at Week 52 and Week 104
Description	Nuclear opacity refers to the opacity in the central nucleus of the eye.The range for NO is 0.1 (no opacity) to 6.9 (maximum opacity). Change from baseline in NO was calculated by subtracting the baseline value from the Week 52 or Week 104 value.
Time Frame	Baseline, Week 52, and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	130	251
Left eye, Week 52; n=130, 251	0.12 (0.498)	0.06 (0.495)
Left eye, Week 104; n=104, 198	0.21 (0.538)	0.10 (0.506)
Right eye, Week 52; n=130, 251	0.12 (0.511)	0.06 (0.492)
Right eye, Week 104; n=104, 198	0.21 (0.550)	0.09 (0.531)

8. Secondary Outcome

Title	Change From Baseline in Nuclear Color (NC) at Week 52 and Week 104
Description	Nuclear color is associated with the force required to compress a lens to 75% of its original depth. The range for NC is 0.1 (no opacity) to 6.9 (maximum opacity). Change from baseline in NC was calculated by subtracting the baseline value from the Week 52 or Week 104 value.
Time Frame	Baseline, Week 52, and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	130	251
Left eye, Week 52; n=130, 251	0.14 (0.432)	0.09 (0.402)
Left eye, Week 104; n=104, 198	0.21 (0.454)	0.13 (0.465)
Right eye, Week 52; n=130, 251	0.16 (0.422)	0.09 (0.410)
Right eye, Week 104; n=104, 198	0.22 (0.452)	0.13 (0.469)

9. Secondary Outcome

Title	Change From Baseline in Intraocular Pressure (IOP) at Weeks 52 and 104
Description	An event for IOP is defined as an increase of 7 mm Hg or greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry. Participants without post-baseline ophthalmic exam data were censored at the randomization date. Change from baseline was calculated by subtracting the baseline value from the Week 52 or Week 104 value.
Time Frame	Baseline, Week 52, and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	An event for IOP is defined as an increase of 7 mm Hg or greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry. Participants without post-baseline ophthalmic exam data were censored at the randomization date. Change from baseline was calculated by subtracting the baseline value from the Week 52 or Week 104 value.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	130	251
Left eye, Week 52; n=130, 251	-0.5 (2.04)	-0.3 (2.26)
Left eye, Week 104; n=104, 198	-0.8 (1.98)	-0.6 (2.41)
Right eye, Week 52; n=130, 251	-0.7 (2.08)	-0.4 (2.33)
Right eye, Week 104; n=104, 198	-1.0 (2.17)	-0.7 (2.55)

10. Secondary Outcome

Title	Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) by Increments of 1 mm Hg at Week 52
Description	An event for IOP is defined as an increase of 7 mm Hg or greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry. Participants without post-baseline ophthalmic exam data were censored at the randomization date. Change from baseline was calculated by subtracting the baseline value from the Week 52 value.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	130	251
Left eye, IOP = <-10 to -9	1 0.6%	0 0%
Left eye, IOP = -8	0 0%	0 0%
Left eye, IOP = -7	0 0%	2 0.5%
Left eye, IOP = -6	0 0%	0 0%
Left eye, IOP = -5	3 1.7%	3 0.8%
Left eye, IOP = -4	5 2.8%	12 3.3%
Left eye, IOP = -3	9 5%	19 5.2%
Left eye, IOP = -2	18 9.9%	40 10.9%
Left eye, IOP = -1	22 12.2%	40 10.9%
Left eye, IOP = 0	36 19.9%	50 13.6%
Left eye, IOP = 1	20 11%	30 8.2%
Left eye, IOP = 2	7 3.9%	24 6.5%
Left eye, IOP = 3	5 2.8%	19 5.2%
Left eye, IOP = 4	4 2.2%	7 1.9%
Left eye, IOP = 5	0 0%	3 0.8%
Left eye, IOP = 6	0 0%	2 0.5%
Left eye, IOP = 7	0 0%	0 0%
Left eye, IOP = 8	0 0%	0 0%
Left eye, IOP = 9	0 0%	0 0%
Left eye, IOP >= 7	0 0%	0 0%
Left eye, IOP >= 10	0 0%	0 0%
Left eye, IOP >= 15	0 0%	0 0%
Right eye, IOP = <-10 to -9	0 0%	0 0%
Right eye, IOP = -8	0 0%	1 0.3%
Right eye, IOP = -7	2 1.1%	0 0%
Right eye, IOP = -6	0 0%	1 0.3%
Right eye, IOP = -5	2 1.1%	4 1.1%
Right eye, IOP = -4	7 3.9%	14 3.8%
Right eye, IOP = -3	9 5%	23 6.3%
Right eye, IOP = -2	25 13.8%	43 11.7%
Right eye, IOP = -1	22 12.2%	34 9.3%
Right eye, IOP = 0	28 15.5%	46 12.5%
Right eye, IOP = 1	16 8.8%	31 8.4%
Right eye, IOP = 2	13 7.2%	27 7.4%
Right eye, IOP = 3	3 1.7%	14 3.8%
Right eye, IOP = 4	2 1.1%	8 2.2%
Right eye, IOP = 5	1 0.6%	2 0.5%
Right eye, IOP = 6	0 0%	3 0.8%
Right eye, IOP = 7	0 0%	0 0%
Right eye, IOP = 8	0 0%	0 0%
Right eye, IOP = 9	0 0%	0 0%
Right eye, IOP >= 7	0 0%	0 0%
Right eye, IOP >= 10	0 0%	0 0%
Right eye, IOP >= 15	0 0%	0 0%

11. Secondary Outcome

Title	Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) by Increments of 1 mm Hg at Week 104
Description	An event for IOP is defined as an increase of 7 mm Hg or greater from baseline in IOP, in either eye, using Goldmann Applanation Tonometry. Participants without post-baseline ophthalmic exam data were censored at the randomization date. Change from baseline in IOP was calculated by subtracting the baseline value from the Week 104 value.
Time Frame	Baseline and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	104	198
Left eye, IOP = <-10 to -9	0 0%	0 0%
Left eye, IOP = -8	0 0%	1 0.3%
Left eye, IOP = -7	0 0%	0 0%
Left eye, IOP = -6	2 1.1%	3 0.8%
Left eye, IOP = -5	0 0%	7 1.9%
Left eye, IOP = -4	6 3.3%	10 2.7%
Left eye, IOP = -3	15 8.3%	19 5.2%
Left eye, IOP = -2	17 9.4%	31 8.4%
Left eye, IOP = -1	15 8.3%	32 8.7%
Left eye, IOP = 0	21 11.6%	32 8.7%
Left eye, IOP = 1	19 10.5%	30 8.2%
Left eye, IOP = 2	5 2.8%	16 4.4%
Left eye, IOP = 3	3 1.7%	7 1.9%
Left eye, IOP = 4	0 0%	6 1.6%
Left eye, IOP = 5	1 0.6%	2 0.5%
Left eye, IOP = 6	0 0%	1 0.3%
Left eye, IOP = 7	0 0%	1 0.3%
Left eye, IOP = 8	0 0%	0 0%
Left eye, IOP = 9	0 0%	0 0%
Left eye, IOP >= 7	0 0%	1 0.3%
Left eye, IOP >= 10	0 0%	0 0%
Left eye, IOP >= 15	0 0%	0 0%
Right eye, IOP = <-10 to -9	0 0%	0 0%
Right eye, IOP = -8	0 0%	1 0.3%
Right eye, IOP = -7	0 0%	2 0.5%
Right eye, IOP = -6	2 1.1%	1 0.3%
Right eye, IOP = -5	5 2.8%	7 1.9%
Right eye, IOP = -4	4 2.2%	15 4.1%
Right eye, IOP = -3	10 5.5%	17 4.6%
Right eye, IOP = -2	24 13.3%	32 8.7%
Right eye, IOP = -1	21 11.6%	22 6%
Right eye, IOP = 0	12 6.6%	46 12.5%
Right eye, IOP = 1	16 8.8%	23 6.3%
Right eye, IOP = 2	6 3.3%	13 3.5%
Right eye, IOP = 3	1 0.6%	8 2.2%
Right eye, IOP = 4	1 0.6%	5 1.4%
Right eye, IOP = 5	1 0.6%	2 0.5%
Right eye, IOP = 6	1 0.6%	2 0.5%
Right eye, IOP = 7	0 0%	2 0.5%
Right eye, IOP = 8	0 0%	0 0%
Right eye, IOP = 9	0 0%	0 0%
Right eye, IOP >= 7	0 0%	2 0.5%
Right eye, IOP >= 10	0 0%	0 0%
Right eye, IOP >= 15	0 0%	0 0%

12. Secondary Outcome

Title	Change From Baseline in Logarithm of the Minimum Angle of Resolution (LogMAR) Visual Acuity (VA) Using Early Treatment Diabetic Retinopathy Study (ETDRS) Charts at Week 52 and Week 104
Description	ETDRS charts are used to measure VA (the ability to resolve fine image details). Participants must have had a best-corrected distance VA of =< 0.18 on the LogMAR scale using ETDRS charts in both eyes measured separately. The LogMAR scale (expressed as the [decadic] logarithm of the minimum angle of resolution [range from +1.00 to -0.30]) converts the geometric sequence of a traditional chart to a linear scale. It measures VA loss; positive values indicate vision loss, whereas negative values denote normal or better VA. A lower LogMAR value indicates better VA.
Time Frame	Baseline, Week 52, and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	130	251
Left eye, Week 52; n=130, 251	-0.027 (0.0729)	-0.013 (0.0778)
Left eye, Week 104; n=104, 198	-0.035 (0.0740)	-0.023 (0.0858)
Right eye, Week 52; n=130, 251	-0.023 (0.0810)	-0.014 (0.0852)
Right eye, Week 104; n=104, 198	-0.025 (0.0992)	-0.024 (0.0899)

13. Secondary Outcome

Title	Percent Change From Baseline in the Funduscopic Horizontal Cup-to-disc Ratio at Week 104
Description	The funduscopic horizontal cup-to-risk ratio assesses the progression of glaucoma. Percent change from baseline in funduscopic horizontal cup-to-disc ratio at Week 104 was calculated by substracting the baseline value from the Week 104 value (both expressed as a percent). The cup-to-disc ratio compares the diameter of the "cup" portion of the optic disc with the total diameter of the optic disc. A large cup-to-disc ratio may imply glaucoma or other pathology.
Time Frame	Baseline and Week 104

Outcome Measure Data

Analysis Population Description

ITT Population. The number analyzed reflects those participants remaining in the study and contributing data at the indicated time points.

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	104	198
Left eye	0.0 (7.23)	0.7 (7.58)
Right eye	0.0 (7.31)	0.0 (7.39)

14. Secondary Outcome

Title	Change From Baseline in the Daily Reflective Total Nasal Symptom Score (rTNSS) for the Indicated Study Periods
Description	rTNSS was evaluated on a 4-point categorical scale (sum of the scores for rhinorrhea, nasal congestion, nasal itching, and sneezing; range=0-12). The data collected were used as a measure for treatment compliance. The scores on the scale were based on the severity of each nasal symptom: 0=none (symptom is not present); 1=mild (sign/symptom is clearly present but minimal awareness; easily tolerated); 2=moderate (definite awareness of sign/symptom that is bothersome but tolerable); 3=severe (sign/symptom is hard to tolerate; causes interference with activities of daily living and/or sleeping).
Time Frame	Baseline, Weeks 1 to 26, Weeks 27 to 52, Weeks 53 to 78, and Weeks 79 to 104

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.	FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
Measure Participants	181	367
Week 1 to 26	-2.12 (0.17)	-3.19 (0.12)
Week 27 to 52	-2.52 (0.21)	-3.86 (0.15)
Week 53 to 78	-2.56 (0.23)	-3.89 (0.16)
Week 79 to 104	-2.59 (0.25)	-4.10 (0.18)
Week 1 to 104	-2.30 (0.18)	-3.45 (0.13)

Adverse Events

Arm/Group Title	Placebo		FF 110 mcg QD
Arm/Group Description	The matching placebo nasal spray containing only fluticasone furoate (FF) vehicle was self-administered as two sprays per nostril each morning once daily (QD) for 104 weeks.		FF nasal spray aqueous suspension contained 0.05% micronized FF. Each spray contained approximately 27.5 micrograms (mcg) of FF; participants self-administered two sprays per nostril each morning QD for a total dose of 110 mcg for 104 weeks.
All Cause Mortality
	Placebo		FF 110 mcg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		FF 110 mcg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/181 (3.9%)		12/367 (3.3%)
Eye disorders
Vitreous floaters	0/181 (0%)		1/367 (0.3%)
General disorders
Chest pain	0/181 (0%)		1/367 (0.3%)
Hepatobiliary disorders
Cholelithiasis	1/181 (0.6%)		0/367 (0%)
Infections and infestations
Pneumonia	0/181 (0%)		1/367 (0.3%)
Injury, poisoning and procedural complications
Contusion	0/181 (0%)		1/367 (0.3%)
Rib fracture	0/181 (0%)		1/367 (0.3%)
Tibia fracture	0/181 (0%)		1/367 (0.3%)
Upper limb fracture	0/181 (0%)		1/367 (0.3%)
Investigations
Blood pressure increased	0/181 (0%)		1/367 (0.3%)
Metabolism and nutrition disorders
Dehydration	0/181 (0%)		1/367 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/181 (1.1%)		0/367 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/181 (0%)		1/367 (0.3%)
Nervous system disorders
Cerebral haemorrhage	0/181 (0%)		1/367 (0.3%)
Convulsion	0/181 (0%)		1/367 (0.3%)
Grand mal convulsion	0/181 (0%)		1/367 (0.3%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/181 (0%)		2/367 (0.5%)
Intra-uterine death	1/181 (0.6%)		0/367 (0%)
Psychiatric disorders
Suicide attempt	1/181 (0.6%)		0/367 (0%)
Renal and urinary disorders
Nephrolithiasis	1/181 (0.6%)		0/367 (0%)
Reproductive system and breast disorders
Cystocele	0/181 (0%)		1/367 (0.3%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/181 (0%)		1/367 (0.3%)
Upper airway obstruction	1/181 (0.6%)		0/367 (0%)
Vascular disorders
Deep vein thrombosis	0/181 (0%)		1/367 (0.3%)
Other (Not Including Serious) Adverse Events
	Placebo		FF 110 mcg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/181 (53.6%)		232/367 (63.2%)
Infections and infestations
Sinusitis	31/181 (17.1%)		47/367 (12.8%)
Upper respiratory tract infection	29/181 (16%)		52/367 (14.2%)
Nasopharyngitis	17/181 (9.4%)		44/367 (12%)
Influenza	16/181 (8.8%)		25/367 (6.8%)
Viral upper respiratory tract infection	12/181 (6.6%)		27/367 (7.4%)
Bronchitis	8/181 (4.4%)		31/367 (8.4%)
Acute sinusitis	7/181 (3.9%)		20/367 (5.4%)
Nervous system disorders
Headache	13/181 (7.2%)		29/367 (7.9%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	34/181 (18.8%)		123/367 (33.5%)
Oropharyngeal pain	9/181 (5%)		23/367 (6.3%)
Nasal ulcer	3/181 (1.7%)		30/367 (8.2%)
Nasal septum ulceration	6/181 (3.3%)		24/367 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

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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.