Two multicenter, randomized, single-blind, single-dose, crossover studies of specific sensory attributes of budesonide aqueous nasal spray and fluticasone propionate nasal spray

Two Multicenter, Randomized, Single-Blind, Single-Dose, Crossover Studies of Specific Sensory Attributes of Budesonide Aqueous Nasal Spray and Fluticasone Propionate Nasal Spray Shailen R. Shah, MD,l Christopher Thomas Uryniak, MS,2 M. Kathryn and Liza O’Dowd, MD2

Miller, MStat,2 Ned Pethick, C. Jones, MA, MSC,~

BS,’

IAllergy and Asthma Consultants of NJ-PA,PC, Collegeville,Pennsylvania, and 2AstraZeneca Le Wilmington, Delaware

ABSTRACT

Background: Intranasal corticosteroids are effective for the treatment of allergic rhinitis. Sensory attributes associated with these sprays may affect patient preference and adherence to treatment regimens. Objectives: These 2 studies compared patients’ perceptions of and preferences for specific sensory attributes of budesonide aqueous nasal spray (BANS) and fluticasone propionate nasal spray (FPNS). Methods: In 2 multicenter, randomized, single-blind (patient), single-dose, 2-period, l-day crossover studies, adults with mild to moderate allergic rhinitis received single doses of BANS (one 32-pg spray per nostril in both studies, 64yg total dose) and FPNS (two 50-yg sprays per nostril in study 1, 2OO+g total dose; one SO-pg spray per nostril in study 2, 100-pg total dose). Study 1 compared the once-daily recommended starting doses of BANS and FPNS, and study 2 compared BANS with half the once-daily recommended dose of FPNS to balance the number of actuations for delivery of study drug. Patients completed the 23-item Sensory Perceptions Questionnaire and indicated their product preference (if any). Results: A total of 110 women and 71 men in study 1 and 136 women and 54 men in study 2 were randomized to treatment. None had previously used BANS or FPNS. In both studies, fewer patients perceived scent or taste (both P < 0.001 in both studies), forceful spray (P < 0.001 in both studies), and a wet feel in both the nose and throat (study 1, P < 0.004; study 2, P < 0.002) with BANS Accepted for publication June 11, 2003. Printed in the USA. Reproduction in whole or part is not permitted.

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S.R.Shah et al.

than with FPNS. In addition, more patients in both studies liked the spray force (study 1, P < 0.01; study 2, P < 0.001) and moisture content in the throat (study 1, P < 0.001; study 2, P < 0.006) of BANS and indicated a greater overall satisfaction with the sensory features of BANS than those of FPNS (study 1, P c: 0.001; study 2, P < 0.015). In analyses that included all responding patients, 54.4% of patients in study 1 preferred BANS and 37.8% preferred FPNS (P < 0.022). In study 2, 47.4% preferred BANS and 41.1% preferred FPNS (not significant). Of the 92.2% of patients in study 1 and 88.4% in study 2 who specified a product preference, 59.0% preferred BANS and 41.0% preferred FPNS in study 1 (P = 0.021), and 53.6% preferred BANS and 46.4% preferred FPNS in study 2 (not significant). Conclusions: On the basis of perceptions of specific sensory attributes reported after 1 administration in these 2 studies, BANS was rated as more pleasing and preferred over the recommended QD starting dose of FPNS, and was also rated as more pleasing than half the QD recommended starting dose of FPNS. (Chin Tvzev: 2003;25:2198-2214) Copyright 0 2003 Excerpta Medica, Inc. Key words: budesonide aqueous, fluticasone propionate, nasal spray, patient preference, sensory attributes.

INTRODUCTION

Allergic rhinitis is a common medical condition that affects -10% to 15% of the US population.’ Although allergic rhinitis affects both children and adults, it is most prevalent among persons aged 20 to 40 years.’ Therefore, a significant proportion of men and women in the workforce are affected.2 The symptoms of allergic rhinitis (ie, sneezing, rhinorrhea, and nasal congestion) produce physical discomfort and have a detrimental impact on patients’ psychological, social, and vocational lives.3 Furthermore, the discomfort and cognitive impairment associated with allergic rhinitis reduce work productivity4 and account for millions of lost days of work each year.5 Although 70% of patients use prescription medication to treat the symptoms of allergic rhinitis, -25% experience inadequate symptom control.6 This lack of optimal symptom control could be a result of ineffective treatment, poor patient adherence, or both. Medications that are ineffective at relieving symptoms; produce undesirable effects such as drowsiness, headache, or burning and stinging in the nose; or have a disagreeable scent or taste may reduce patients’ willingness to adhere to their treatment regimens. This may in turn, reduce the effectiveness of the prescribed allergy product. Intranasal corticosteroids are an efficacious pharmacologic therapy for the treatment of allergic rhinitis. They successfully reduce nasal congestion, rhinorrhea, sneezing, and itching in most patients, and available data suggest that intranasal corticosteroids are more effective than oral antihistamines7J As a result, topical cor2199

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ticosteroids administered via nasal sprays are being used increasingly as first-line therapy for the relief of symptoms of allergic rhinitis9J0 Moreover, recent guidelines developed by a joint task force on the practice parameters in allergy, asthma, and immunology1 l and by the Allergic Rhinitis and its Impact on Asthma workshop in collaboration with the World Health Organizationlo have recommended the use of nasal corticosteroids in all patients except those with occasional or the mildest of allergic rhinitis symptoms. Intranasal corticosteroids for the treatment of allergic rhinitis were introduced to the market -3 decades ago. l2 Since then, advances in formulations and delivery methods have become important factors when selecting a treatment.13 Early formulations were delivered via pressurized metered-dose inhalers (pMDI$, whereas the present formulations include aqueous products such as budesonide aqueous nasal spray* (BANS) and fluticasone propionate nasal spray+ (FPNS). BANS was designed to provide additional comfort to patients with sensitive mucosa who may have been unable to tolerate the pMD1 formulations.r4 BANS also has a low volume of spray (one 50-uL spray per nostril QD) for treatment delivery and does not contain a chlorofluorocarbon propellant or alcohol, both of which may cause burning or stinging in the nose. Moreover, BANS does not contain benzalkonium chloride, a preservative with antimicrobial properties that is known to have a bitter taste; other corticosteroid nasal sprays, such as FPNS, contain this compound.15 Although subtle differences may exist, intranasal corticosteroids show similar efficacy and safety for treating the symptoms of allergic rhinitis when administered at the recommended daily doses. 16-18 Success or failure of the treatment and proper management of the symptoms depend on patient adherence to an established schedule initiated by the prescribing physician. Sensory attributes are increasingly important to patients and may affect their preference for intranasal products, especially when medications prove to be similar in efficacy Therefore, when patients prefer the specific sensory attributes associated with a particular intranasal corticosteroid formulation or delivery device, they may better adhere to a treatment regimen. The primary objectives of the studies reported here were to compare patients’ perceptions of and preferences for specific sensory attributes of BANS and FPNS. PATIENTS

AND

METHODS

Study Design

Two multicenter, randomized, single-blind (patient), single-dose, 2-period, lday crossover studies were conducted (AstraZeneca studies RAQ-1002 [study 11 and RAQ-1003 [study 21). Study 1 consisted of 12 investigational sites, and study *Trademark: Rhinocort Aqua@ (AstraZeneca LP, Wilmington, Delaware). ‘Trademark: Flonase@ (GlaxoSmithKline, Research Mangle Park, North Carolina)

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2 consisted of 13 sites within the United States. Eligible patients were screened at an initial visit and were enrolled for randomization and treatment on the same day or within 7 days of screening. In study 1, the recommended (labeled) QD starting doses of BANS (one 32-yg spray per nostril, equal to 64-ug total dose) and FPNS (two 50-pg sprays per nostril, equal to 200~pg total dose) were used. Study 2 compared the same dose of BANS with half the recommended once-daily starting dose of FPNS (one 50-pg spray per nostril, equal to 100~ug total dose) to balance the number of actuations for delivery of study drug. To eliminate bias due to order of treatment, we assigned patients to 1 of the 2 possible treatment sequences (BANS followed by FPNS or FPNS followed by BANS) in balanced blocks at each site according to a randomization schedule generated in advance by a centralized computer at AstraZeneca. Investigators at each site assigned numbers (corresponding to randomized assignment to a treatment sequence) to patients sequentially as they qualified for the study, thus ensuring that patients were randomly assigned to a treatment sequence in balanced blocks at each site. This process resulted in the same designated maximum number of patients at each site that could be enrolled in the study but varying total numbers of patients at each site. Before receiving study medication, patients in study 1 briefly rinsed their mouths with a small cup of water. Patients in study 2 chewed unsalted crackers, briefly rinsed their mouths with a small cup of water, and then smelled a swatch of wool. Patients then self-administered the study treatments under supervision from a professional at the investigational site after instructions were given on the proper technique of nasal spray use. Study 1 included a l-hour washout period and study 2 included a 2-hour washout period between dosing. These washout periods between single administrations of each product were chosen based on previous studies investigating patients’ preferences of sensory attributes of nasal products lg and inhaled asthma medications20; results of these studies showed that washout periods of 30 to 45 minutes were sufficient. Although the investigators were not blinded, patients were blinded to the identity of the treatment by removal or covering of the labels on the spray bottles, along with removal of the distinctively colored caps. In addition, patients were eligible for the study only if they had not previously used either medication. Both studies received approval from an independent ethics committee or institutional review board, and all enrolled patients provided written informed consent before treatment. Patient

Population

Patients enrolled were of either sex, were aged 218 years, had H-year history of allergic rhinitis (seasonal or perennial), and were experiencing mild to moderate symptoms of allergic rhinitis as determined by a 24-hour reflective total nasal symptom score on the study day In addition, all participants had a history of ei2201

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ther inadequate control of symptoms with antihistamines, decongestants, and/or immunotherapy, or previous success with intranasal corticosteroids other than budesonide or fluticasone propionate. Exclusion criteria were the following: pregnancy, nursing, or not using an accepted method of birth control; the presence of nasal candidiasis, rhinitis medicamentosa, atrophic rhinitis, acute or chronic rhinitis, and nasal obstructions or abnormalities; a significant disease history or unstable medical condition; the use of topical nasal corticosteroid treatment within 2 weeks before study initiation; a history of hypersensitivity or intolerance to corticosteroids (topical or systemic); use of medications that could mask the symptoms of rhinitis immediately after the study treatment day; use of an experimental drug within 30 days preceding study initiation; or previous use of BANS or FPNS. Sensory Perceptions Questionnaire

Immediately after each treatment session, patients were placed in a predesignated waiting area and instructed not to discuss their impressions of the treatment while completing the 23-item Sensory Perceptions Questionnaire (SPQ).21 The self-administered SPQ was developed and validated in collaboration with 2 healthoutcomes research groups (Avalon Health Solutions, Inc., Philadelphia, Pennsylvania, and Psychometric Technologies, Hillsborough, North Carolina) and was presented in 2 parts. Part I was administered to the patients after the first spray treatment to record their perceptions of specific sensory attributes of the treatment. After a washout period (1-2 hours) and administration of the second treatment, Part I of the SPQ was again administered to record their perceptions of the second spray, followed by Part II to determine their overall (global) preference, if any, for either treatment based on the sensory attributes of the products. Part I of the SPQ consisted of a list of 5 yes/no questions about whether they perceived any scent, taste, aftertaste, medicine rundown into the throat, or runout from the nose. Next, an additional 16 questions were presented, and ?-point Likert scales were used to rate each patient’s degree of perception and like/dislike of each attribute (1 = strongest perception and greatest disliking; 5 = weakest perception and greatest liking). Attributes included the same 5 qualities as for the yes/no questions plus force and liking of the force of spray, and feel and liking of the spray in the nose and throat. The last question in Part I asked the patients, “Overall, how pleased were you with the sensory features of the nasal spray you just used?” on a 5-point Likert scale (1 = very displeased; 5 = very pleased). Part II of the SPQ asked those patients who completed the entire study the following global preference question: “Based on the sensory features of the 2 study sprays you used today, overall, which study spray did you prefer?” Patients responded by indicating either the first or second spray or no preference. The questions in Part I of the SPQ are listed in Table I. 2202

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Table I. Part I of the Sensory Perceptions Questionnaire. Response

Question Preliminary

questions

I. Did the nasal spray have any smell?

Yes/no

2.

Did the nasal spray have any taste?

Yes/no

3.

Did any medicine run down the back of your nose into your throat?

Yes/no

4.

Did any medicine run out of your nostrils?

Yes/no

5.

Did the nasal spray have an aftertaste?

Yes/no

Follow-up

questions*

I a. Strength of the smell

Very strong ( I )-very

I b. Liking of the smell

Disliked a lot (I)-liked

2a. Strength of the taste

Very strong ( I )-very

2b. Liking of the taste

Disliked a lot (I)-liked

3a. Amount

Extreme amount

of medicine that ran into your throat

3b. How much were you bothered

by the medicine

of medicine that ran out of your nostrils

4b. How much were you bothered

a lot (5) weak (5) a lot (5)

(I)-minimal

bothered

(I)-not

amount

(5)

bothered

at all (5)

running into your throat? 4a. Amount

Extremely

weak (5)

by the medicine

Extreme amount Extremely

(I)-minimal

bothered

(I)-not

amount

(5)

bothered

at all (5)

running out of your nostrils?

Very strong ( I )-very

5a. What was the force of the spray?

weak (5)

5b. Extent to which you liked/disliked the force of Disliked a lot (I)-liked

the spray

Very dry (I)-very

6a. How did the spray feel in your nose? 6b. Extent to which you liked/disliked

how the spray Dislilced a lot (I )-liked

felt in your nose 7a. How did the spray feel in your throat 7b. Extent to which you liked/disliked

after use?

Very dry (I)-very

a lot (5)

moist (5)

how the spray Disliked a lot (I)-liked

felt in your throat 8a. Opinion

a lot (5)

moist (5)

Very strong (I )-very

of the strength of the aftertaste

a lot (5) weak (5)

Disliked a lot (I)-liked

8b. Liking of the aftertaste

a lot (5)

Final question* Overall, how pleased were you with the sensory features of the nasal spray you just used? “Patients rated their degree of perception ception

Statistical

Very displeased (I)-very

and like/dislike of each attrlbute

and greatest dislike; 5 = weakest perception

pleased (5)

using Lilcert scales (I = strongest per-

and greatest liking).

Analyses

the design of each study we estimated that - 155 evaluable patients would provide 80% power to detect a treatment difference of 0.125 in the proportion of patients preferring 1 of the treatments with the use of a 2-tailed l-sample test for proportions. In

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In each study, the primary end point was patient preference. Study 1 and study 2 results from the global patient preference question (Part II of the SPQ) were analyzed with the Mainland-Gart test (stratified by site) and also with the Prescott test (stratified by site) to include patients who did not express a preference for 1 product over the other. 22-24 Binary (yes/no) responses for the patients’ perceptions of specific sensory attributes from questions in Part I of the SPQ were analyzed with the Mainland-Gart test, and ordinal responses (Likert scale) with the Wilcoxon signed rank test. All statistical comparisons were performed as 2-sided tests. Statistical significance was set at P I 0.05. Safety

Safety was assessed in each patient who received 21 treatment spray The safety assessment was based on clinical evaluation by the study investigators and by patient self-monitoring of adverse events (AEs). AEs were reported on the study day and in a follow-up telephone call 2 weeks after treatment to inquire about any additional events. RESULTS Patient

Population

A total of 181 patients underwent randomization and received treatment in study 1 (110 women, 71 men); 1 patient was lost to follow-up (safety assessment) but completed the SPQ, and another patient was determined to have a protocol deviation after receiving the study drug and completing the SPQ. In study 2, a total of 190 patients (136 women, 54 men) underwent randomization, received treatment, and completed the entire study Demographic characteristics were well balanced between the 2 studies (Table II). Sensory Perceptions

Questionnaire

Part I

In study 1 (BANS 64 ug vs FPNS 200 ug), patients were significantly less likely to perceive any scent (P < O.OOl>, taste (P < O.OOl>, aftertaste (P < O.OOl), medicine rundown into the back of the nose and into the throat (P < O.OOl), or medicine runout of the nostrils (P < 0.019) when using BANS compared with FPNS (Figure 1A). In study 2 (BANS 64 p.g vs FPNS 100 pg), patients were also significantly less likely to perceive any scent or taste (both P < 0.001) when using BANS compared with FPNS (Figure 1B); no significant differences were found between products for aftertaste, medicine rundown into the back of the nose and into the throat, or medicine runout from the nostrils. Patients rated their sensory perceptions and the degree of their perceptions and their like or dislike of those perceptions using Likert scales (Figures 2 and 3). Study 1 (BANS 64 yg vs FPNS 200 pg) and study 2 (BANS 64 pg vs FPNS 100 ug) both 2204

S.R. Shah et al.

Table II. Demographics and baseline characteristics of patients randomized to treatment in studies I and 2. Study Characteristic

I

Study 2

(N = 181)

(N = 190)

I IO (60.8)

I36 (7 I .6)

71 (39.2)

54 (28.4)

Sex, no. (%) Women Men Agel Y Mean Range

40

38

I 8-73

I 8-80

125 (69.1)

I44 (75.8)

(I 6.0) 2 I (I I .6)

33 (I 7.4)

Race, no. (%) White

29

Blacl< Hispanic

8 (4.2)

Asian

6 (3.3)

2 (Ll)

Other

0 (0.0)

3 (1.6)

Baseline total nasal symptom Mean Range

score* 7

7 3-12

4-l

I

Allergic rhinitis duration, y Seasonal and perennial Mean

I9

I8

Range

l-58

I-62

Perennial Mean

I6

I3

Range

3-49

2-30

Seasonal Mean Range

I4

18

I47

l-50

‘Based on the sum of patient-reported individual nasal symptom scores of rhinorrhea, sneezrng,nasal congestion, and nasal itching (O-l 2 total scale). Higher scores indicate more severe symptoms.

showed that more patients perceived the feel of spray in the throat as less wet with BANS than with FPNS (Figure 2; study 1, P < 0.004; study 2, P < 0.002), and more patients preferred the feel of the spray in the throat with BANS than with FPNS (Figure 3; study 1, P < 0.001; study 2, P < 0.006). In addition, more patients in both studies perceived the feel of spray in the nose as less wet with BANS than with FPNS (Figure 2; study 1, P < 0.001; study 2, P < O.OOl), and more patients preferred the feel of spray in the nose with BANS than with FPNS (Figure 3; study 1, P < 0.001; study 2, P < 0.001). More patients in both studies perceived a less force2205

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W BANS 0 FPNS

* -

t

Scent

Taste (n = 179)

(n = 181)

Aftertaste

Throat

(n = 181)

Rundown

II. Nose

(n = 181)

Runout

(n = 181)

W BANS 0 FPNS

r

*

!..I. :

Scent

Taste (n = 189)

(n = 190)

Figure

I. Percentages sensory

of patients

attributes

propionate

responding

of budesonide

Aftertaste (n = 187)

Throat

Nose

Rundown

Runout

(n = 190)

(n = 190)

yes when asked if they perceived

specific

aqueous nasal spray (BANS) and fluticasone

nasal spray (FPNS) in (A) study

I (BANS 64 wg vs FPNS 200 kg)

and (B) study 2 (BANS 64 Fg vs FPNS IO0 pg). *P < 0.00 I; tP C 0.0 19. 2206

S.R. Shah et al.

0

Very moist or very weak (5) Somewhat moist or somewhat weak (4)

m

Neither

dry nor moist: neither strong nor weak (3)

?? Somewhat dry or somewhat strong (2) 0

Very dry or very strong (I)

A Mean Score

3.1

3.4+

2.7

BANS

FPNS

3.3*

80 60 40 20 0 BANS

BANS

FPNS

FPNS

Feel in Nose

Feel in Throat

Spray Force

6 Mean Score

3.2

3.4*

100 80 60 40 20 0 BANS

FPNS

Feel in Throat

BANS

FPNS

BANS

Feel in Nose

FPNS

Spray Force

Figure 2. Mean Likert scores for degree of perception of specific sensory attributes of budesonide aqueous nasal spray (BANS) and fluticasone propionate nasal spray (FPNS) in (A) study I (BANS 64 pg vs FPNS 200 Fg) and (B) study 2 (BANS 64 p,g vs FPNS 100 Fg). *P < 0.004; l’p C 0.001; *P < 0.002.

ful spray with BANS than with FPNS (Figure 2; study 1, P < 0.001; study 2, P < O.OOl>, and more patients preferred the force of spray with BANS than with FPNS (Figure 3; study 1, P < 0.002; study 2, P < 0.001). Finally, when patients were asked, “Overall, how pleased were you with the sensory features of the nasal spray you just used?” a greater majority of patients in both studies were very pleased or somewhat pleased with BANS than with FPNS (Figure 4; study 1, P < 0.001; study 2, P < 0.015).

The remaining questions in Part I of the SPQ were follow-up items to the preliminary questions. As a result, if a patient responded no to a preliminary question, he or she would be instructed not to answer the corresponding follow-up 2207

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THERAPEUTICS@

0 Like a lot (5) Like somewhat (4) Neither like nor dislike (3) ?? Dislike somewhat (2) 0 Dislike a lot (I) A

Mean Score

3.4*

3.1

3.6*

3.3

Y

100

100

‘52

80

80

;

60

60

%I :!

40

40

$

20

20

2

0

BANS

FPNS

Feel in Throat

BANS

FPNS

0

Feel in Nose

BANS

FPNS

Spray Force

B Mean Score 3

3.2+

3.0*

3.5*

3.1

100

80

80

60

60

4Oi

40

20

20

01

BANS

FPNS

Feel in Throat

Figure 3.

3.5*

100

Mean

Likert

BANS

FPNS

Feel in Nose

0

3.1

1

BANS

FPNS

Spray Force

scores for like/dislike of specific sensory attributes of budesonide

aqueous nasal spray (BANS) and fluticasone propionate nasal spray (FPNS) for (A) study I (BANS 64 pg vs FPNS 200 pg) and (B) study 2 (BANS 64 pg vs FPNS IO0 pg).*P < 0.00I ; l-P < 0.002; *P c 0.006.

questions, Because the number of evaluable patients for these follow-up questions was relatively small compared with the total number of all randomized patients in each study, and because this population was biased (ie, selected based on the answer to a preliminary question), formal statistical analyses of these data were not performed. However, the responses to these questions favored BANS, as did the preliminary yes/no questions for these items.

Part II of the SPQ asked patients the global preference question, “Based on the sensory features of the 2 sprays you used today, overall, which study spray did 2208

S.R.Shah et al.

A H BANS ? ?FPNS

100 90 80

IO 0

I

Very Pleased or Somewhat Pleased

Very Displeased or Somewhat Displeased

Neither Pleased nor Displeased

B ?? BANS

100

0

FPNS

90 80 $ c .$ c?

70

z a,

50

3 c $ [Lfz

60

II

40 30 20 IO 01-

Very Pleased or Somewhat Pleased

Figure 4. Patients’ overall

satisfaction

Neither Pleased nor Displeased

based on the sensory

aqueous nasal spray (BANS) and fluticasone (A) study

Very Displeased or Somewhat Displeased

propionate

features

of budesonide

nasal spray (FPNS) in

I (BANS 64 kg vs FPNS 200 pg [mean scores, 3.9 BANS vs 3.5

FPNS; P < 0.00 I]) and (B) study 2 (BANS 64 pg vs FPNS IO0 pg [mean scores, 3.8 BANS vs 3.5 FPNS; P 4 0.0) 51). 2209

CLINICALTHERAPEUTICS@

you prefer?” Of the 181 randomized patients in study 1, 180 (99.4%) completed this question and were therefore considered evaluable for the analysis of preference. Of this group, 166 (92.2%) expressed a preference for 1 of the 2 randomized treatments and were included in the primary analysis of preference. Significantly more patients preferred BANS (98 patients, 59.0%) than FPNS (68 patients, 41.0%) (P = 0.021; Figure SA). When the analysis included patients who completed the global preference question but did not express a preference for either product (14 patients, 7.8%), significantly more patients preferred BANS over FPNS (54.4% vs 37.8%; P <: 0.022; Figure 5B). Patients preferred BANS to FPNS regardless of the order of administration of the 2 study drugs. However, the patients who were randomized to receive BANS first indicated a stronger preference for BANS over FPNS than those patients who received BANS second, although this difference was not assessed for statistical significance. Patients who received the study drugs in the BANS-FPNS sequence preferred BANS to FPNS 61.1% to 34.4% (4.4% had no preference). Patients who received the FPNS-BANS sequence preferred BANS to FPNS 47.8% to 41.1% (11.1% had no preference). In study 2, all 190 randomized patients were considered evaluable for the analysis of preference. Of this group, 168 (88.4%) expressed a preference for 1 of the 2 randomized treatments and were included in the primary analysis of preference. Ninety patients (53.6%) preferred BANS compared with 78 (46.4%) who preferred FPNS, but these values were not significantly different (Figure SC). When patients were included who did not express a preference for either product (22 patients, 11.6%), these values remained nonsignificant (Figure 5D). Patients who received the study drugs in the BANS-FPNS sequence preferred BANS to FPNS 52.6% to 35.1% (12.4% had no preference; statistical significance not assessed). Those who received the FPNS-BANS sequence preferred FPNS to BANS 47.3% to 41.9% (10.8% had no preference; statistical significance not assessed). Variation among sites was observed in both studies with respect to patients’ responses to the global preference question (Part II of the SPQ). In study 1, at 5 of the 11 sites, >50% of patients preferred BANS; at 3 sites, equal numbers of patients preferred BANS or FPNS; and at the remaining 3 sites, >50% of patients preferred FPNS. In study 2, 7 of the 13 sites had more patients who preferred BANS, and 6 sites had more patients who preferred FPNS. Safety Profile

BANS and FPNS were well tolerated in both studies. Overall, AEs were few, mild to moderate in severity, and similarly distributed across treatment sequences. Nine patients in study 1 (5.0%) and 11 patients in study 2 (5.8%) reported an AE. In study 1, no AEs were judged to be causally related to the study treatment. In study 2, 7 AEs were judged to be treatment related (rhinitis [n = 41, dry mouth [n = 11, nausea [n = 11, and headache [n = 11). No serious or significant AEs were 2210

S.R.Shah et al.

Figure 5. Percentages

of patients

expressing

aqueous nasal spray (BANS) neither, based on sensory

a global preference

or fluticasone

features, in study

propionate

for either

budesonide

nasal spray (FPNS), or

I (BANS 64 kg vs FPNS 200 kg)

and study 2 (BANS 64 p,g vs FPNS IO0 kg). (A) Study I results, based on I66 evaluable

patients

all 180 patients who expressed responded.

who expressed who

responded.

a preference.

a preference.

(B) Study I results, based on

(C) Study 2 results, based on I68 patients

(D) Study 2 results, based on all I90 patients who

*P = 0.02 I ; tP -z 0.022.

reported in either study and no significant noted in any patient.

clinical changes in vital signs were

DISCUSSION

These 2 multicenter, randomized, single-blind (patient) studies found that these patients were significantly less likely to perceive any scent, taste, aftertaste, or 2211

CLINICAL THERAPEUTICS@

medicine rundown into the throat or out of the nostrils with the recommended QD starting dose of BANS than with FPNS. These studies also showed that BANS was associated with a significantly less forceful and more likable force of spray, a drier and more likable feel of spray in the nose and throat, and overall a more pleasant assessment of sensory features than FPNS in the population studied. In support of the present findings, another aqueous intranasal corticosteroid, triamcinolone acetonide nasal spray, was also preferred over FPNS and mometasone furoate in a multicenter study using a nasal spray evaluation questionnaire.25 In the present studies, we did not attempt to assess patients’ preference for 1 product over another based on differences in efficacy or safety profile, nor did we attempt to assess overall patient satisfaction with BANS as compared with FPNS. These attributes cannot be adequately assessed in a single-exposure treatment design. These studies were designed to assess overall preference based on the patients’ perceptions of all relevant sensory attributes associated with the use of a nasal corticosteroid spray By design, the SPQ did not include items to assess AEs such as nasal irritation or epistaxis because these events would not be expected to occur immediately after a single exposure. These studies were also not designed to compare the safety of the 2 treatments, although we determined the incidence of AEs as reported by the patients. Very few of the reported AEs were judged to be treatment related; however, the physicians evaluating these reported AEs were not blinded to treatment, so there was a possibility of bias. The overall incidence of AEs reported by the blinded patients was low and similar across treatment sequences. Patient adherence to a prescribed treatment regimen is essential for adequate management of disease symptoms. Adherence is especially important for treating the symptoms of allergic rhinitis, for which preventive administration of intranasal corticosteroids is recommended to achieve successful long-term symptom management.lO Previous reports have shown that patients’ perceptions of the sensory attributes and ease of administration of intranasal corticosteroids are important considerations when prescribing a specific treatment regimen, along with the traditional factors of effectiveness and safety 19,25,26For example, FPNS contains benzalkonium chloride, a preservative known to have a bitter taste, and phenylethyl alcohol, an additive known to have a floral scent, whereas BANS does not contain either additive. The presence of these compounds may have contributed to the larger number of patients in both study 1 and study 2 who described only FPNS as having a taste or scent. The recommended starting dose of BANS requires only one SO-pL spray per nostril QD, whereas both recommended daily doses of FPNS consist of two lOOpL sprays per nostril daily (2 sprays per nostril QD or 1 spray per nostril BID).27 The lower spray volume of BANS may have contributed to the significant differences in study 1 (but not study 2) seen between BANS and FPNS in the perception of medicine rundown into the throat and medicine runout from the nostrils. 2212

S.R. Shahet al.

CONCLUSIONS On the basis

of perceptions

of specific

sensory

attributes

reported

after 1 admin-

istration in these 2 studies, BANS was rated as more pleasing and preferred over the recommended QD starting dose of FPNS, and was also rated as more pleasing than

half the QD recommended

starting

dose of FPNS.

ACKNOWLEDGMENTS This

study

was

Christopher Media,

supported

Tobias,

PhD,

Pennsylvania),

by a financial and

Stella

contributed

grant

Chow,

provided

PhD

by AstraZeneca

(Tri-Med

to the preparation

LP.

Communications,

of the manuscript.

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Address correspondence Consultants of NJ-PA, PC, 19426. 2214

to: 555

Shailen Second

(SAR).

R. Shah, MD, Allergy and Asthma Avenue, Suite C-750, Collegeville, PA