1. Rhinitis, sinusitis, and ocular diseases
Fluticasone furoate nasal spray: A single
treatment option for the symptoms
of seasonal allergic rhinitis
Harold B. Kaiser, MD,a
Robert M. Naclerio, MD,b
John Given, MD,c
Tom N. Toler,
PharmD,d
Anna Ellsworth,d
and Edward E. Philpot, MDd
Minneapolis, Minn, Chicago, Ill,
Canton, Ohio, and Research Triangle Park, NC
Background: Fluticasone furoate (USAN-approved name) is
a novel, enhanced-affinity glucocorticoid administered in a
unique side-actuated device for the management of seasonal
allergic rhinitis (SAR).
Objective: We sought to evaluate the efficacy and safety of
once-daily fluticasone furoate nasal spray, 110 mg, in patients
aged 12 years or older with fall SAR.
Methods: Patients (n 5 299) received fluticasone furoate or
placebo for 2 weeks in this double-blind, parallel-group
randomized study. Patients evaluated nasal and ocular
symptoms using a 4-point categoric scale. Efficacy was assessed
on the basis of the mean change from baseline in reflective and
instantaneous total nasal symptom scores and reflective total
ocular symptom scores.
Results: Fluticasone furoate produced significantly greater
improvements than placebo in daily reflective total nasal
symptom score (21.473, P < .001; primary end point), morning
predose instantaneous total nasal symptom score (21.375, P <
.001), daily reflective total ocular symptom score (20.600, P 5
.004), and patient-rated overall response to therapy (P < .001).
The onset of therapeutic effect occurred at 8 hours after initial
administration. Fluticasone furoate was well tolerated.
Conclusion: Fluticasone furoate, 110 mg once daily, was
effective and well tolerated for the treatment of nasal symptoms
of SAR in patients aged 12 years and older. Treatment also
produced significant improvements in ocular symptoms.
Fluticasone furoate was fast acting, as indicated by an 8-hour
onset of action, and provided 24-hour symptom control.
Clinical implications: New treatments for the bothersome
symptoms of SAR are needed. One such treatment, fluticasone
furoate nasal spray, provides effective relief of the symptom
profile of SAR. (J Allergy Clin Immunol 2007;119:1430-7.)
Key words: Intranasal corticosteroids, fluticasone furoate, seasonal
allergic rhinitis, ragweed pollen
Allergic rhinitis (AR), a major chronic upper respira-
tory tract disorder, occurs as a consequence of an IgE-
mediated immune reaction to 1 or more environmental
allergens.1
The cumulative symptom burden of AR can
have detrimental effects on emotional and social well-
being, quality of life, performance, and productivity.2-4
Combined with increasing rates of prevalence,5-7
this
makes AR a major public health concern.
Studies pertaining to pathophysiology show that the
IgE-mediated inflammatory response is characterized by
early- and late-phase reactions after allergen exposure.1
Allergens stimulate mast cells and, subsequently, cause
T lymphocytes and eosinophils to infiltrate the nasal epi-
thelium. These cells release proinflammatory mediators
and give rise to mucosal venous congestion, neural stimu-
lation, and the characteristic symptoms of AR.8
Depending on the timing and type of allergen involved
in triggering the allergic response, AR can be either
perennial or seasonal (SAR).6,9
Patients with SAR experi-
ence symptomatic exacerbations primarily during pollen
seasons. In the United States symptoms of SAR are pro-
foundly severe during the fall ragweed season. Up to 10%
of the total US population is sensitized to ragweed, with
this allergy accounting for approximately 50% of all cases
of pollinosis in atopic individuals.10,11
During the peak
ragweed season, typically between August and October,
the concentrations of ragweed in the air can reach 800
grains/m3
.12
SymptomsofARcanoccurwithairconcentra-
tions as little as 5 to 10 pollen grains/m3
,13
thus establishing
ragweed as a major seasonal source of allergenic proteins.
Of concern, in 2002, a climate study demonstrated that rag-
weed pollen production increased 61% after a doubling
From a
the Clinical Research Institute, Minneapolis; b
the Pritzker School
of Medicine, University of Chicago, Chicago; c
private practice, Canton;
and d
GlaxoSmithKline, Research Triangle Park.
Supported by GlaxoSmithKline R&D Ltd.
Disclosure of potential conflict of interest: H. B. Kaiser has received grant
support from Alcon, Allergy Therapeutics, Altana, AstraZeneca, Boehringer
Ingelheim, Cobolis, Centocor, Dynavax, GlaxoSmithKline, Genentech,
Novartis, Merck, 3M, Sanofi-Aventis, Schering-Plough, SkyePharma, Med-
Point, IVAX, and Almirall and is on the speakers’ bureau for Merck, Novar-
tis, GlaxoSmithKline, and Schering-Plough. R. M. Naclerio has consulting
arrangements with GlaxoSmithKline, Schering, Aventis, Inspire, Novartis,
and Merck; has received grant support from Schering, GlaxoSmithKline,
Novartis, Alcon, and Merck; is on the speakers’ bureau for Merck; and
has served as an expert witness in a couple of malpractice cases unrelated
to allergic rhinitis. T. N. Toler, A. Ellsworth, and E. E. Philpot are employed
by GlaxoSmithKline. J. Given has declared that he has no conflict of
interest.
Received for publication November 15, 2006; revised February 8, 2007;
accepted for publication February 16, 2007.
Available online April 6, 2007.
Reprint requests: Harold B. Kaiser, MD, Clinical Research Institute, 825
Nicollet Mall, Suite 1135, Minneapolis, MN 55402. E-mail: hbk@allergy-
asthma-docs.com.
0091-6749/$32.00
Ó 2007 American Academy of Allergy, Asthma & Immunology
doi:10.1016/j.jaci.2007.02.022
1430
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2. Abbreviations used
AE: Adverse event
AR: Allergic rhinitis
ECG: Electrocardiogram
HRQOL: Health-related quality of life
INS: Intranasal corticosteroid
iTNSS: Instantaneous total nasal symptoms score
QD: Once daily
RQLQ: Rhinoconjunctivitis Quality-of-Life Questionnaire
rTNSS: Reflective total nasal symptom score
rTOSS: Reflective total ocular symptom score
SAR: Seasonal allergic rhinitis
of CO2 concentrations, suggesting that the incidence of
ragweed-induced AR is likely to increase in the future.14,15
A number of pharmacologic interventions exist for the
treatment of AR. Intranasal corticosteroids (INSs) inhibit
the onset of the inflammatory response and reduce the
permeability of the nasal mucosa, the number of inflam-
matory cells, and the release of mediators.16
The proved
efficacy and safety of INSs, combined with their ability
to act on both the early- and late-phase inflammatory
responses, establishes INSs as the first-line therapy in
patients with moderate-to-severe AR.17
In particular, the
American Academy of Allergy, Asthma & Immunology
recommends INSs as first-line therapy when nasal con-
gestion is a major component of the patient’s AR.18
The
Allergic Rhinitis and its Impact on Asthma guidelines
recommend intranasal steroids for patients with moder-
ate-to-severe symptoms.6
Fluticasone furoate (USAN-approved name), a novel,
enhanced-affinity glucocorticoid with potent anti-inflam-
matory activity19-21
administered in a unique side-actu-
ated device, represents a new treatment for AR. Data
from a phase IIb dose-ranging study demonstrated flutica-
sone furoate, 110 mg once daily (QD), as the optimal dose
for improving nasal symptoms of AR while maintaining
good tolerability in adult and adolescent patients with
SAR.22,23
At this dose, fluticasone furoate also had a
beneficial effect on ocular symptoms.23
To confirm the results of the dose-ranging study, the
current phase III trial was designed to investigate the
efficacy of fluticasone furoate nasal spray, 110 mg QD, for
alleviating the nasal and ocular symptoms of SAR during
the fall ragweed season.
METHODS
This was a randomized, double-blind, placebo-controlled, paral-
lel-group study performed in the United States during the 2005 fall
ragweed allergy season (August-October). The study protocol was
approved by a national institutional review board or local university
institutional review boards and carried out in accordance with Good
Clinical Practice and the Declaration of Helsinki. All patients, or the
parent/guardian of those aged less than 18 years, provided written
informed consent before study participation.
Patients aged 12 years and older were recruited from 17 centers
located predominantly in the US Midwest, where exposure to
ragweed allergen was expected to be significant during the study
period. Pollen counting was performed by an expert reference
laboratory using Rotorod (Multidata, Plymouth Meeting, Pa) samples
received from each center twice weekly throughout the entire treat-
ment period to accurately track the pollen season and limit intersite
variation in sample analysis. Sites began collecting air samples for
pollen analysis 4 weeks before the predicted season and were directed
individually to initiate screening when pollen counts reached a thresh-
old level of 10 to 15 grains/m3
. This monitoring process ensured the
study was conducted during the peak season and that pollen levels
at each site remained greater than the pollen threshold throughout
the study. Patients were not permitted to travel outside their geo-
graphic region for more than 48 hours.
Patients were required to have a documented history of SAR
caused by ragweed pollen, with seasonal allergy symptoms during
each of the past 2 fall allergy seasons and a positive skin prick test
response to ragweed allergen within the 12 months before the start of
the study. In addition, only those with moderate-to-severe nasal and
ocular symptoms were eligible for inclusion.
To determine symptom severity, patients rated individual nasal
and ocular symptoms on a diary card using a 4-point categoric scale:
0, none; 1, mild; 2, moderate; and 3, severe. To be randomized,
patients were required to be clinically symptomatic, with a mean daily
reflective total nasal symptom score (rTNSS; the sum of the
individual nasal symptom scores for nasal congestion, rhinorrhea,
nasal itching, and sneezing) of 6 or greater, a mean daily reflective
nasal symptom score for congestion of 2 or greater, and a mean daily
reflective total ocular symptom score (rTOSS; the sum of the
individual ocular symptom scores for itching/burning eyes, tearing/
watering eyes, and eye redness) of 4 or greater, all measured over
four 24-hour periods. In addition, patients had to have completed
80% of their screening period (5-21 days) assessments on a screening
diary card (Fig 1). Diary cards recorded severity of patient symptoms
before randomization by scoring nasal and ocular symptoms as pre-
viously described to ensure eligibility for inclusion into the study.
Patients were excluded from participation in the study if a
significant concomitant medical condition was evident, including
uncontrolled disease of any body system, severe physical nasal
obstruction or injury, asthma, rhinitis medicamentosa, bacterial or
viral infection within 2 weeks of the study, acute or significant
chronic sinusitis, glaucoma and/or cataracts or ocular herpes simplex,
Candida species infection of the nose, any psychiatric disorder, or
adrenal insufficiency. Patients were also excluded if they had re-
ceived a systemic or inhaled corticosteroid within 8 weeks before
the first visit, any INSs within 4 weeks before the first visit, other
allergy medications within specified time frames chosen to ensure
no continued effect on symptoms, or any other medications that could
affect AR or the effectiveness of the study drug. Neither contact
lenses nor the use of any ocular preparations (including artificial tears,
eyewash/irrigation solutions, or lubricants) were permitted.
Patients who met the inclusion/exclusion criteria and the minimum
symptom criteria were randomized to receive 2 weeks’ treatment with
either fluticasone furoate nasal spray, 110 mg QD, or a matched
vehicle placebo nasal spray administered as 2 sprays from the device
into each nostril every morning. Patients were not permitted to take
any antiallergy or rhinitis medication during the study.
Patients were instructed to score and document their symptoms in
a reflective and instantaneous manner. The reflective assessments
captured the severity of symptoms over the previous 12 hours and
were performed each morning and evening just before the next daily
dose (morning) and approximately 12 hours after that daily dose
(evening). The instantaneous assessments were performed just before
administering the morning dose and provided information on the
efficacy of treatment at the end of the 24-hour dosing interval.
The total nasal and ocular symptom scores were summed from the
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3. individual symptom scores to provide rTNSS and rTOSS symptoms
at morning and evening time points and instantaneous total score for
nasal symptoms (iTNSS) and instantaneous total ocular symptom
scores at the end of the 24-hour dosing interval. The daily rTNSSs and
rTOSSs were calculated from the average of the morning and evening
assessments. Additionally, patients were instructed to record their
iTNSSs at 4, 6, 8, 10, and 12 hours after the first dose of study drug.
At the last study visit, patients assessed their overall response to
therapy by answering the following question using a 7-point categoric
scale (significantly improved, moderately improved, mildly im-
proved, no change, mildly worse, moderately worse, and significantly
worse): How would you rate the effectiveness of the study drug for
relieving your AR symptoms over the entire treatment period?
Health-related quality of life (HRQOL) was assessed with the
Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ), a 28-
item self-administered questionnaire that assesses HRQOL (activi-
ties, sleep, nonnose/noneye symptoms, practical problems, nasal
symptoms, emotional problems, and eye symptoms) over a 1-week
period.24
Each question was scored on a scale of 0 to 6 (higher scores
indicate greater HRQOL impairment). The RQLQ was completed
before drug administration and reassessed at the end of the treatment
period or on the occasion of early withdrawal.
Safety was assessed by monitoring vital signs and performing
12-lead electrocardiograms (ECGs), clinical laboratory tests, and
physical examinations at screening and treatment end. Nasal exam-
inations were carried out at all visits. All adverse events (AEs) were
recorded from screening through to the follow-up telephone call
made 3 to 5 days after the last visit.
The primary efficacy end point was the mean change from baseline
over the entire treatment period in daily rTNSS. Key secondary
efficacy end points were the mean change from baseline over the
entiretreatmentperiodindailyrTOSS,themeanchangefrombaseline
over the entire treatment period in the morning predose iTNSS,
and the overall evaluation of response to therapy. HRQOL (measured
by using the RQLQ) was also assessed as an end point. Other
secondary efficacy end points measured included the mean change
from baselinein total and individual reflective and instantaneous nasal
and ocular symptoms and time to onset of effect, as well as the mean
percentage change in daily rTNSSs and rTOSSs and morning predose
iTNSSs and instantaneous total scores for ocular symptoms. Throat/
palatal itching was assessed as an exploratory end point.
A sample size of 288 patients (with 144 patients in each treatment
group) was calculated by using data from a previous study, which
suggested that it would be reasonable to assume an SD for a mean
change from baseline over the entire treatment period in daily rTNSS
of 2.6. By using a 2-sample t test with a 2-sided significance level of
.05, the proposed sample size should provide 90% power to detect a
difference of 1.0 between active treatment and placebo. All efficacy
assessments were carried out on the intent-to-treat population, which
comprised all randomized patients who received at least 1 dose of
the study drug. The primary analysis method was the comparison of
treatment groups (fluticasone furoate, 110 mg, vs placebo) by using
an analysis of covariance with adjustments for baseline rTNSS, inves-
tigative site, age, and sex. Secondary efficacy measures of nasal and
nonnasal symptoms were analyzed similarly. Overall evaluation of re-
sponse to therapy was analyzed with logistic regression, adjusting for
age,sex,investigativesite,andtreatment.Fordeterminationofonsetof
action, mean change from baseline in morning predose iTNSS at 4, 6,
8, 10, and 12 hours after the first dose of study drug was analyzed by
using a repeated-measures model, adjusting for baseline iTNSS, age,
sex, treatment, investigator, time, and treatment-by-time interaction.
Multiplicity adjustments were made for the results from the primary
and key secondary efficacy analyses. The primary efficacy end point
served as gatekeeper for the interpretation of treatment comparisons
for the key secondary efficacy and health outcomes end points.
Analyses were performed in a sequential manner to control for multi-
plicity across the key secondary efficacy and health outcomes end
points as follows: (1) mean change from baseline over the entire treat-
ment period in morning predose iTNSS; (2) overall evaluation of
response to therapy; and (3) the end points of mean change from
baseline over the entire treatment period in daily rTOSS and mean
change from baseline to end point in the global score of the RQLQ
were controlled at the 0.05 level by using Hochberg’s method. Study
randomization was stratified by site to account for any variability.
RESULTS
Study population
A total of 428 patients were screened, of whom 299
were randomized and evaluated as the intent-to-treat
population. Ninety-six percent of patients completed the
FIG 1. Study design.
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4. study; reasons for withdrawal were similar between the
treatment and placebo groups, although withdrawal be-
cause of AEs (2 patients) or lack of efficacy (2 patients)
occurred only in patients in the placebo group. Patient
demographics and baseline characteristics were similar
between the 2 treatment groups (Table I). Patients were
mainly white and between 18 and 65 years of age, and
71% had SAR for 10 years or longer. The mean daily
rTNSS (9.6 6 1.56 for fluticasone furoate and 9.9 6
1.33 for placebo) and rTOSS (6.6 6 1.44 for fluticasone
furoate and 6.5 6 1.47 for placebo) over the 4 days before
randomization were similar between treatment groups, as
was the mean daily exposure of patients to ragweed pol-
len during both screening and the 2-week study period.
Mean ragweed exposure ranged from 26.0 to 64.7 pollen
grains/m3
during screening, 18.5 to 42.7 pollen grains/m3
during week 1, and 10.6 to 25.7 pollen grains/m3
during
week 2. Mean pollen counts exceeded 20 grains/m3
for
most of the studyperiod. Overthe 2 weeks oftreatment, ap-
proximately 88% of patients were compliant to study med-
ication in both treatment groups on the basis of patient
diary cards.
Efficacy
For the primary efficacy end point (mean change from
baseline in daily rTNSS), fluticasone furoate, 110 mg,
significantly reduced nasal symptoms compared with
placebo, with an observed treatment difference of
21.473 (P < .001; Fig 2, A) over the entire treatment pe-
riod. Similarly, an observed difference of 20.600 (P 5
.004, Fig 3) between the treatment groups was recorded
for the mean change from baseline in daily rTOSS over
the treatment period. These observed differences corre-
spond to a mean percentage change from baseline of
221.59% in the placebo group and 235.63% in the fluti-
casone furoate group (a difference of 214.04%) for daily
rTNSS and 225.37% in the placebo group and
234.21% in the fluticasone furoate group (a difference
of 28.626%) for daily rTOSS.
Once-daily dosing with fluticasone furoate, 110 mg,
was supported, with efficacy demonstrated at 24 hours
after the dose on the basis of a significant reduction in
morning predose iTNSS of 21.375 (P < .001; Fig 2, B)
compared with placebo over the entire treatment period.
For the onset of action assessment, the first significant
treatment difference in morning predose iTNSS between
fluticasone furoate and placebo was observed at 8 hours
after the first dose (20.696, P < .028). A significant treat-
ment difference was maintained from day 1 throughout the
remaining study.
These results were reaffirmed by each of the individual
nasal and ocular symptom score reductions, with greater
reductions for fluticasone furoate than for placebo over the
entire treatment period (P < .001 and P .033, respec-
tively; Tables II and III). For the exploratory end point
of throat/palatal itching, the mean changes from baseline
were also statistically in favor of fluticasone furoate for
daily reflective (20.249, P 5 .001) and morning predose
instantaneous (20.237, P 5 .002) assessments.
The treatment difference in the overall response to
therapy was significant (P .01). Seventy-three percent of
patients receiving fluticasone furoate compared with only
52% of patients receiving placebo reported improvement
in their overall evaluation of response to therapy.
Significant/moderate improvement was reported by 42%
of patients receiving fluticasone furoate compared with
21% of those receiving placebo.
Patients receiving fluticasone furoate also experienced
significant improvements in the overall RQLQ score
over those receiving placebo (20.606, P .001), which
achieved or exceeded the minimally important difference
of 0.5, indicating a clinically meaningful improvement in
their overall quality of life.
Safety and tolerability
Fluticasone furoate, 110 mg QD, was well tolerated. No
serious AEs occurred during the study, and no safety
issues of clinical importance were identified from nasal
examinations, vital signs, laboratory values, or ECGs.
AEs occurred in 21% and 12% of patients in the
fluticasone furoate and placebo groups, respectively. The
most common AE was headache, which was the only
event that occurred at an incidence of greater than 3% and
was more common in the fluticasone furoate group than in
the placebo group (Table IV). Six (4%) patients in the
TABLE I. Patient demographics and baseline characteris-
tics in an intent-to-treat population
Placebo
(n 5 148)
Fluticasone
furoate, 110 mg
(n 5 151)
Total
(n 5 299)
Age (y)
Mean, SD 34.5, 14.09 35.4, 13.85 35.0, 13.95
Minimum-maximum 12-74 12-70 12-74
Age groups, n (%)
12 to 18 y 27 (18) 22 (15) 49 (16)
18 to 65 y 119 (80) 128 (85) 247 (83)
65 to 75 y 2 (1) 1 (1) 3 (1)
Sex, n (%)
Female 84 (57) 96 (64) 180 (60)
Male 64 (43) 55 (36) 119 (40)
Race, n (%)
White 129 (87) 139 (92) 268 (90)
Black 16 (11) 10 (7) 26 (9)
Other 3 (2) 2 (1) 5 (2)
Symptom scores,
mean (SD)
TNSS
Daily reflective 9.9 (1.33) 9.6 (1.56) 9.8 (1.45)
Morning
instantaneous
9.3 (1.61) 9.4 (1.65) 9.4 (1.63)
Morning reflective 9.8 (1.39) 9.6 (1.64) 9.7 (1.53)
Evening reflective 9.9 (1.44) 9.8 (1.54) 9.8 (1.50)
TOSS
Daily reflective 6.5 (1.47) 6.6 (1.44) 6.5 (1.45)
Morning
instantaneous
6.3 (1.63) 6.6 (1.56) 6.5 (1.60)
Morning reflective 6.4 (1.53) 6.6 (1.47) 6.5 (1.50)
Evening reflective 6.5 (1.52) 6.7 (1.50) 6.6 (1.51)
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5. active group and 2 (1%) patients in the placebo group had
drug-related AEs, the most common of which were
headache and epistaxis. One patient receiving placebo
withdrew from the study because of a nasopharyngitis
(common cold). The incidence of laboratory abnormali-
ties was low and similar between the 2 treatment
groups. All changes in vital signs, nasal examinations,
and ECGs were minor and similar across the 2 treatment
groups.
DISCUSSION
This study demonstrated that treatment with fluticasone
furoate, 110 mg QD, is effective for alleviating the nasal
symptoms of SAR (nasal congestion, itching, rhinorrhea,
and sneezing) in adults and adolescents. Efficacy was also
demonstrated in the relief of ocular symptoms (eye
watering/tearing, eye itching/burning, and eye redness).
The response to treatment was characterized by a fast
onset, with significant improvement in nasal symptoms
compared with that seen in the placebo group as early as 8
hours after the first dose that continued consistently over
the course of the study. Fluticasone furoate also provided
relief of nasal symptoms over the entire 24-hour dosing
period, as seen on the basis of the significant reductions in
the morning predose symptom scores, providing support
for the QD dosing regimen.
Given that eye symptoms are reported to be present in
60% of patients with AR25
and are notably bothersome,
the statistically significant reduction in the ocular symp-
tom scores with fluticasone furoate over the treatment
period was clinically significant, particularly when com-
pared with the ocular efficacy seen with antihistamines.26
FIG 2. Mean change from baseline in the daily rTNSS (A) and morning predose iTNSS (B) ofpatients treated with
placebo or fluticasone furoate, 110 mg QD, over the 2-week treatment period (in an intent-to-treat population).
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6. Although previously investigated in other studies, older
INSs failed to show consistent efficacy for ocular symp-
toms in adult patients with SAR.27-29
Physicians tend to
coprescribe a topical or systemic agent with the AR drug
regimen to treat allergic eye symptoms.6,18,30
The need
for ancillary treatments might be reduced with an INS
capable of relieving both nasal and ocular symptoms.
Fluticasone furoate nasal spray, 110 mg QD, offers an
opportunity to address this need in AR symptoms.
Allergic ocular symptoms are likely to be the result of
both direct contact with pollen and reflex-generated
symptoms originating from the nose. Although the
FIG 3. Mean change from baseline in the daily rTOSS of patients treated with placebo or fluticasone furoate,
110 mg QD, over the 2-week treatment period (in an intent-to-treat population).
TABLE II. Mean change from baseline over the entire treatment period in daily reflective and morning predose iTNSSs
and individual nasal symptom scores in an intent-to-treat population
Daily reflective Morning predose instantaneous
Nasal symptom
Placebo
(n 5 148)
Fluticasone furoate, 110 mg
(n 5 151)
Placebo
(n 5 148)
Fluticasone furoate, 110 mg
(n 5 151)
TNSS
LS mean change (SE) 22.07 (0.22) 23.55 (0.21) 21.53 (0.21) 22.90 (0.21)
LS mean difference 21.473 21.375
P value .001 .001
95% CI 22.01 to 20.94 21.90 to 20.85
Rhinorrhea
LS mean change (SE) 20.54 (0.06) 20.87 (0.06) 20.38 (0.06) 20.68 (0.06)
LS mean difference 20.331 20.302
P value .001 .001
95% CI 20.48 to 20.18 20.45 to 20.15
Nasal congestion
LS mean change (SE) 20.48 (0.06) 20.84 (0.06) 20.34 (0.05) 20.65 (0.05)
LS mean difference 20.358 20.306
P value .001 .001
95% CI 20.50 to 20.22 20.44 to 20.17
Nasal itching
LS mean change (SE) 20.52 (0.06) 20.86 (0.06) 20.42 (0.06) 20.74 (0.06)
LS mean difference 20.337 20.319
P value .001 .001
95% CI 20.48 to 20.20 20.46 to 20.17
Sneezing
LS mean change (SE) 20.52 (0.06) 20.99 (0.06) 20.38 (0.06) 20.82 (0.06)
LS mean difference 20.475 20.444
P value .001 .001
95% CI 20.63 to 20.32 20.60 to 20.29
LS, Least square; LS mean difference, least-square mean change in fluticasone furoate minus least-square mean change in placebo.
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7. mechanisms by which INSs relieve ocular symptoms have
not been fully characterized, one likely mechanism has
been strongly considered: modulation of a naso-ocular
neurogenic reflex. It is, however, unlikely that the ob-
served effect of fluticasone furoate on ocular symptoms
results from systemic action, either through absorption of
minor amounts of swallowed drug or through absorption
into the nasal mucosa. Fluticasone furoate has been shown
to work topically with a low absolute bioavailability
(0.50%), which results from the drug’s poor aqueous
solubility, limited mucosal contact time with the nose, and
extensive first-pass metabolism.31
Furthermore, flutica-
sone furoate has previously shown no treatment-related
trends or dose-response effect on 24-hour urinary cortisol
excretion and no systemic adverse reactions.22
After 2 weeks’ therapy with fluticasone furoate, pa-
tients experienced statistically and clinically meaningful
improvements in overall quality of life (as determined by
improvements in RQLQ) that corresponded with the
improvements in symptom severity. The symptoms of
SAR have been shown to have a significant effect on
quality of life, and therefore any improvements in quality
of life should help to reduce disease burden.4,32
Data from this study support the safety of fluticasone
furoate, 110 mg QD, in this population of patients with
SAR. Although headache was the most commonly
reported AE, this condition is common in clinical trials
and the general population and is not an expected drug-
related effect of fluticasone furoate. The incidence of
epistaxis was low in this study (2% for fluticasone furoate
vs 1% for placebo). Overall, no safety or tolerability
issues of clinical importance were identified from AE
reporting, nasal examinations, vital signs, laboratory
values, or ECG results after treatment.
In conclusion, the results of this large, randomized
placebo-controlled trial demonstrate that fluticasone furo-
ate nasal spray, 110 mg QD, is well tolerated and effective
in the relief of nasal symptoms in adult and adolescent
patients with ragweed-induced SAR. The totality of data
from this study confirms that fluticasone furoate, 110 mg
QD, is indeed an appropriate therapeutic dosage; this
shows consistency with the dose-ranging study conducted
in adult and adolescent patients with SAR.22,23
Moreover,
the QD dose led to improvements in ocular symptoms and
meaningful improvements in overall quality of life in this
study. Based on our findings, fluticasone furoate nasal
spray, 110 mg QD, might present a single treatment option
for the nasal and ocular symptoms of SAR.
Data reviewed in this manuscript correspond to study number
FFR104861. We thank the members of the FFR104861 GSK study
team for their contribution to this study, including Susan Cheer, PhD,
and Anna Koundouris, PhD, for writing assistance and manuscript
management.
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Eye itching/burning
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P value .033
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Eye tearing/watering
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P value .001
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Eye redness
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