- Email: [email protected]
Placebo-controlled, double-blind study of the efficacy and safety of triamcinolone acetonide aerosol nasal inhaler in pediatric patients with seasonal allergic rhinitis
CLINICAL THERAPEUTICSVVOL.
18, NO. 2, 1996
Placebo-Controlled, Double-Blind Study of the Efficacy and Safety of ‘Ikiamcinolone Acetonide Aerosol Nasal Inhaler in Pediatric Patients with Seasonal Allergic Rhinitis Charles Andrew John A. John A.
H. Banov, MD,’ William S. Silvers, MD,2 W. Green, MD,3 Julius H. van Bavel, MD,4 Winder MD,5 Gary Feiss, MS,6 Brandon Simpsorq4 Furst,dand Joseph A. Smith, MD6
‘Allergy & Asthma Centers of Charleston, PA., North Charleston, South Carolina, 2Allergy, Asthma & Immunology Clinic of Colorado, F!C., Englewood, Colorado, 3Adult and Pediatric Allergy, West Seneca, New York, 4Allergy Associates of the Austin Diagnostic Clinic, Austin, Texas, sAllergy & Asthma Research Center Toledo, Ohio, and 6RhBne-Poulenc Rorer Pharmaceuticals Inc., Collegeville, Pennsylvania
ABSTRACT Triamcinolone acetonide (TAA) aerosol nasal inhaler has been shown to effectively relieve the symptoms of seasonal allergic rhinitis in adults and adolescents. We conducted a study to evaluate the efficacy and safety of once-daily administration of TAA aerosol nasal inhaler in pediatric patients aged 6 to 11 years with grass seasonal allergic rhinitis. This multicenter, randomized, double-blind, placebocontrolled, parallel-group study enrolled 116 children who were treated with either TAA aerosol nasal inhaler (220 kg/d) or placebo once daily for 2 weeks. Patients evaluated the severity of rhinitis symptoms (nasal stuffiness, discharge, sneezing, and itching) daily according to a four-
0149-2918/96/$3.50
point scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Patients’ and physicians’ global evaluations of overall treatment efficacy were assessed at the end of the 2-week treatment period. Patients treated with TAA aerosol nasal inhaler had significantly greater reductions in all nasal symptom scores overall and in virtually all symptoms at the end of week 1 and week 2 compared with those in the placebo group. Both patients’ and physicians’ global evaluations of efficacy favored TAA aerosol nasal inhaler over placebo. This study demonstrated that once-daily administration of 220 pg of TAA aerosol nasal inhaler was well tolerated and effectively reduced the symptoms of seasonal allergic rhinitis in pediatric patients.
265
CLINICAL THERAPEUTICS”
INTRODUCTION Intranasal corticosteroids are highly effective in relieving the symptoms associated with both seasonal and perennial allergic rhinitis. 1A Additionally, topical formulations of synthetic corticosteroids have considerably reduced the systemic side effects and potential effects on adrenocortical function associated with systemic corticosteroid use.3,4 Triamcinolone acetonide (TAA) aerosol nasal inhaler,* the first intranasal corticosteroid approved in the United States for once-daily administration, has been shown to effectively reduce symptoms of seasonal and perennial allergic rhinitis with no measurable systemic effects, limited adverse events, and no measurable effects on adrenocortical function.5-11 The recommended starting dose for patients 12 years of age and older is 220 l.i,g/d. If adequate control is not achieved, the dose can be increased to a maximum of 440 kg/d. Once symptoms are controlled, some patients can be effectively maintained on 110 l,r,g/d.Although several studies have examined the safety and effectiveness of TAA aerosol nasal inhaler in populations that included young children with perennial allergic rhinitis” and adolescents with seasonal and perennial allergic rhinitis,“8,10 none specifically targeted seasonal allergic rhinitis symptoms with a once-daily, 220-pg TAA aerosol nasal inhaler dosing regimen in patients younger than age 12 years. Our study was designed to determine whether symptoms of seasonal allergic rhinitis in a pediatric population can be safely and effectively
*Trademark: Nasacort@ (RhBne-Poulenc Rorer Pharmaceuticals Inc., Collegeville, Pennsylvania).
266
reduced with once-daily administration 220 pg of TAA aerosol nasal inhaler.
PATIENTS
of
AND METHODS
Boys and premenarcheal girls aged 6 to 11 years with a l-year history of seasonal allergic rhinitis, a positive response to a skin prick test for grass allergens, and a minimum qualifying total rhinitis symptom (nasal stuffiness, nasal discharge, sneezing, and nasal itching) score of 24 points (out of a possible 48 points) were enrolled in the study. Patients were excluded for any clinically relevant deviation from normal medical or laboratory values, nasal candidiasis, acute sinusitis, or a history of hypersensitivity to corticosteroids. Patients also were excluded if they had been treated with nasal, inhaled, or systemic corticosteroids within 42 days of study enrollment; nasal cromolyn sodium within 14 days; an investigational drug within 90 days; or a medication that might produce or relieve the signs and symptoms of allergic rhinitis. Patients who had begun immunotherapy within 30 days of study enrollment or had participated in any previous TAA aerosol nasal inhaler study were excluded. The investigational protocol was approved by an institutional review board at each study site, and informed, written consent was obtained from each parent or guardian. This multicenter (five US centers), randomized, double-blind, placebo-controlled, parallel-group study was designed to compare the efficacy and safety of oncedaily administration of 220 p,g of TAA aerosol nasal inhaler with that of placebo in pediatric patients with grass seasonal allergic rhinitis. The study consisted of a screening/baseline peTiod fol-
C.H. BANOV ET AL.
lowed by a 2-week treatment period. The study was conducted during the grass pollen season, between the months of April and July. During the initial screening visit (5 to 14 days before randomization), the patient’s medical and drug history were recorded; a skin prick test, physical examination, and laboratory tests were performed; and mucous membranes were examined for signs of fungal infection. Diary cards were distributed to record daily nasal symptom scores (stuffiness, discharge, sneezing, and itching), concomitant medications, adverse events, and compliance with the prescribed study medication regimen. The severity of daily rhinitis symptoms was rated according to the following four-point scale: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. Symptoms were rated once daily in the evening and reflected symptom severity over the previous 24 hours. If the aggregate sum of the rhinitis symptom scores for 4 days preceding randomization was 24 points or more (out of a possible 48 points), the patient was randomized to one of two treatment groups. Patients received either 220 pg of TAA aerosol nasal inhaler (55 pg per puff) or placebo administered as 2 puffs in each nostril every morning for 14 days. New diary cards were distributed at this baseline visit and at the end of week 1; diaries were collected and reviewed after week 1 and at the final visit after the 2-week treatment period. At the final visit, medical and laboratory examinations were performed and global evaluations of treatment efficacy were recorded by the patient and the investigator according to the following scale: 0 = greatly improved, 1 = somewhat improved, 2 = no change, 3 = somewhat worsened, and 4 = greatly worsened.
Statistical Analyses The primary efficacy variables evaluated for this study were the mean changes from baseline in the daily symptom ratings for nasal stufftness, nasal discharge, sneezing, and the nasal index (the sum of these three symptom scores). Mean changes from baseline were averaged for each week separately and for the entire 2-week treatment period. Secondary efficacy variables included nasal itching and patients’ and investigators’ global evaluations of overall efficacy. The statistical model was a twoway analysis of variance with treatment and investigator as main effects and no interaction term. Differences between treatment groups were analyzed using a onesided t test. Statistical significance was set at an alpha level of 0.05.
RESULTS One hundred sixteen patients, 74 boys and 42 girls, were enrolled in the study. Fiftyeight patients were included in each treatment group; 65% and 62% of patients in the TAA aerosol nasal inhaler and placebo groups, respectively, were boys. Demographic characteristics were similar for both groups. Overall, the mean age was 9 years (range, 6 to 1 I years), with 93% of the study population white and 7% black. One hundred fifteen of the 116 patients completed the 2-week treatment period. One patient in the placebo group discontinued treatment after 8 days because the medication canister was empty despite using the medication as prescribed. One hundred fourteen of the 116 patients enrolled had evaluable data and were included in the efficacy analyses; results from the intent-totreat analyses did not differ from those obtained in the assessable population.
267
CLINICAL THERAPEUTICS”
Table I. Mean baseline rhinitis symptom scores.*
Symptom Nasal stuffiness Nasal discharge Sneezing Nasal index? Nasal itching
TAA Aerosol Nasal Inhaler (n = 58)
Placebo (n = 56)
Total (n = 114+)
2.19 2.05 1.92 6.16 2.06
2.19 1.83 1.83 5.85 2.07
2.19 1.94 1.88 6.01 2.07
TAA = triamcinolone acetonide. ‘Rhinitis symptom scale: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. +n = number of patients with evaluable data. ‘Nasal index is the sum of symptom scores for nasal stuffiness, nasal discharge,
Efficacy Mean nasal symptom ratings at baseline were similar for the two treatment groups and considered moderate in intensity, with values ranging from 1.83 to 2.19 for nasal stuffiness, nasal discharge, sneezing, and nasal itching (Table I). After 2 weeks of treatment, patients using TAA aerosol nasal inhaler showed statistically significant reductions (P c 0.05) from baseline in nasal stuffiness, nasal discharge, sneezing, nasal index, and nasal itching compared with the placebo group (Table II). The TAA aerosol nasal inhaler group also had significantly greater improvements (P c 0.05) in symptoms during week 1 and week 2 for nasal stuffiness, nasal discharge, nasal index, and nasal itching. Significant improvement (P < 0.05) also was observed during week 2 for sneezing. Daily mean changes from baseline over the 2-week treatment period also were examined for nasal index scores (figure). Beginning at day 2 and continuing throughout the 2-week treatment period,
268
and sneezing.
TAA aerosol nasal inhaler produced progressively larger reductions in nasal index scores compared with placebo. Both patients’ and physicians’ global evaluations of treatment efficacy significantly favored TAA aerosol nasal inhaler over placebo (P < 0.05). Eighty-six percent of patients (50 of 58) treated with TAA aerosol nasal inhaler reported that their nasal symptoms had greatly or somewhat improved compared with 64% of those (36 of 56) in the placebo group. In addition, more physicians reported that patients treated with TAA aerosol nasal inhaler had greatly or somewhat improved symptoms compared with those receiving placebo (72% vs 64%, respectively).
Safety Safety was evaluated for all 116 patients enrolled in the study. No serious adverse events were reported during the study, nor did any patient discontinue treatment because of an adverse event. Thirty-one patients in the TAA aerosol nasal inhaler group and 22 patients in the
C.H. BANOV ET AL.
Table II. Adjusted* changes from baseline in allergic rhinitis symptoms+ in assessable patients over the 2-week treatment period. Values are given as mean + SE. TAA Aerosol Nasal Inhaler” Week 1 (n = 58) Week 2 (n = 57)
Symptom Nasal stuffiness Week 1 Week 2 Overall Nasal discharge Week 1 Week 2 Overall Sneezing Week 1 Week 2 Overall Nasal index” Week
1
Placebos Week 1 (n = 56)
Overall (n = 58)
Week 2 (n = 54) Overall (n = 56)
-060+008”
-0.33
f 0.08
-0:91
+ 0:10n
-0.37
f 0.10
-0.74
r 0.08”
-0.34
r 0.08
-0.67
f 0.095
-0.38
+ 0.09
-1.02
2 0.10”
-0.46
f 0.11
-0.84
f 0.09$
-0.42
f 0.09
-0.57
+ 0.10
-0.34
f 0.10
-0.89
f 0.10”
-0.46
f 0.10
-0.72
zt 0.09”
-0.40
+ 0.10 f 0.20
-I .85 + 0.20”
-1.05
Week 2
-2.82
f 0.24”
-1.30
+ 0.24
Overall
-2.30
+ 0.20”
-1.16
-I- 0.21
Nasal
itching
-0.64 f 0.10”
-0.37
f 0.10
Week 2
-0.95
+ 0.11s
-0.53
+ 0.11
Overall
-0.76
f 0.10”
-0.43
* 0.10
Week
1
TAA = triamcinolone acetonide. *Means adjusted for imbalances among investigators. +Rhinitis symptom scale: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. ‘n = number of patients with evaluable data. “P < 0.05 versus placebo for one-tailed t test. “Nasal index is the sum of symptom scores for nasal stuffiness, nasal discharge,
placebo group reported adverse events; the majority of these events were mild. The most frequently reported adverse events were headache and epistaxis, with both occurring more often in the TAA aerosol nasal inhaler group than in the placebo group. Adverse events indicative of topical effects were minimal and similar for both treatment groups. No fungal infections were detected at baseline or the
and sneezing.
conclusion of the study. No clinically significant changes from baseline in vital signs or laboratory values were observed in either treatment group.
DISCUSSION
AND CONCLUSION
TAA aerosol nasal inhaler is effective and well tolerated by adults and adolescents with symptoms of seasonal or perennial
269
CLINICAL THERAPEUTICS”
0 Placebo 0 TAA aerosol nasal inhaler (220 @d)
E 3
‘-
-1
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-1.5
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-2
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-2.5
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-3
-3.5 , I Baseline 1
I
I
I
I
I
I
I
I
/
I
I
I
1
2
3
4
5
6
7
8
9
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Study Day
Figure.
Daily mean changes (GE) from baseline in the nasal index over the 2-week treatment period. The nasal index is the sum of the symptom scores for nasal stuffiness, nasal discharge, and sneezing. TAA = triamcinolone acetonide.
allergic rhinitis5-to and by children as young as age 4 years with symptoms of perennial allergic rhinitis.” Our study confirms and reinforces the efficacy and safety of once-daily administration of TAA aerosol nasal inhaler in children aged 6 to 11 years to relieve symptoms of seasonal allergic rhinitis. Patients treated with TAA aerosol nasal inhaler had significantly greater reductions (P < 0.05) in all nasal symptom scores after 2 weeks of treatment compared with those receiving placebo. Virtually all nasal symptoms were significantly reduced (P < 0.05) at the end of weeks 1 and 2 in patients treated with TAA aerosol nasal inhaler. Both patients and physicians
270
reported TAA aerosol nasal inhaler to be more favorable than placebo in controlling rhinitis symptoms. Although patients in the TAA aerosol nasal inhaler group in this study reported a higher percentage of adverse events than those in the placebo group, overall findings from other studies of pediatric patients show comparable adverse events between active treatment groups and placebo and no apparent dose-related trends in studies with varying TAA aerosol nasal inhaler dosages.6~8~10*”In addition, other studies8~i0~” have shown that epistaxis is reported more frequently or comparably in patients receiving placebo compared with those treated with TAA aerosol
C.H. BANOV ET AL.
nasal inhaler. While patients treated with TAA aerosol nasal inhaler in our study had a somewhat higher incidence of epistaxis compared with those in the placebo group, these data may be skewed because recurrent epistaxis is especially common in pediatric patients.” Control of seasonal allergic rhinitis symptoms was accomplished with oncedaily administration of medication. Although this is an important consideration with all patients in that multiple daily dosing is associated with patient noncompliance and incomplete therapeutic response, it is especially important when treating children.13,14 From our findings, we concluded that once-daily administration of 220 p,g of TAA aerosol nasal inhaler is a reliable and effective treatment for the symptoms of seasonal allergic rhinitis and is well tolerated by pediatric patients.
ACKNOWLEDGMENT This study was funded in part by RhonePoulenc Rorer Pharmaceuticals Inc., Collegeville, Pennsylvania.
Address correspondence to: Charles H. Banov, MD, 9213A University Boulevard, North Charleston, SC 29406.
REFERENCES I. Druce HM, Kaliner MA. Allergic rhinitis. JAMA. 1988;259:26&263. 2. Mabry RL. Corticosteroids in the management of upper respiratory allergy: The emerging role of steroid nasal sprays. Otolaryngol Head Neck Surg. 1992;107: 855-860.
3. Naclerio
RM. Allergic
rhinitis.
NEJM.
1991;325:860-869. 4. Siege1 SC. Topical intranasal corticosteroid therapy in rhinitis. J Allergy Clin Immunol. 1988;81:984-991. 5. Feiss G, Morris R, Rom D, et al. A comparative study of the effects of intranasal triamcinolone acetonide aerosol (ITAA) and prednisone on adrenocortical function. J Allergy Clin Immunol. 1992;89: 1151-1156. 6. Findlay S, Huber F, Garcia J, Huang L. Efficacy of once-a-day intranasal administration of triamcinolone acetonide in patients with seasonal allergic rhinitis. Ann Allergy. 1992;68:228-232. 7. Spector S, Bronsky E, Chervinsky P, et al. Multicenter, double-blind, placebo-controlled trial of triamcinolone acetonide nasal aerosol in the treatment of perennial allergic rhinitis. Ann Allergy. 1990;64: 300-305. 8. Storms W, Bronsky E, Findlay S, et al. Once daily triamcinolone acetonide nasal spray is effective for the treatment of perennial allergic rhinitis. Ann Allergy. 1991;66:329-334. 9. Tinkelman D, Falliers C, Gross G, et al. Multicenter evaluation of triamcinolone acetonide nasal aerosol in the treatment of adult patients with seasonal allergic rhinitis. Ann Allergy. 1990;64:234-240. 10. Welch MJ, Bronsky EA, Findlay S, et al. Long-term safety of triamcinolone acetonide nasal aerosol for the treatment of perennial allergic rhinitis. Clin Ther. 1994;16:253-262. 11. Welch MJ, Bronsky EA, Grossman J, et al. Clinical evaluation of triamcinolone acetonide nasal aerosol in children with
271
CLINICAL THERAPEUTICS@
perennial allergic 1991;67:493498.
rhinitis.
Ann Allergy.
12. Sly RM. Pediatric Allergy. 2nd ed. Garden City, NY Medical Examination Rublishing Co, Inc;‘1981: 197. 13. Becker MH, Maiman LA. Strategies for enhancing patient compliance. J Community Health. 1980;6: 113-135.
272
14. Cramer JA, Mattson RH, Prevey ML, et al. How often is medication taken as prescribed? A novel assessment technique. JAMA. 1989;261:3273-3277.
18, NO. 2, 1996
Placebo-Controlled, Double-Blind Study of the Efficacy and Safety of ‘Ikiamcinolone Acetonide Aerosol Nasal Inhaler in Pediatric Patients with Seasonal Allergic Rhinitis Charles Andrew John A. John A.
H. Banov, MD,’ William S. Silvers, MD,2 W. Green, MD,3 Julius H. van Bavel, MD,4 Winder MD,5 Gary Feiss, MS,6 Brandon Simpsorq4 Furst,dand Joseph A. Smith, MD6
‘Allergy & Asthma Centers of Charleston, PA., North Charleston, South Carolina, 2Allergy, Asthma & Immunology Clinic of Colorado, F!C., Englewood, Colorado, 3Adult and Pediatric Allergy, West Seneca, New York, 4Allergy Associates of the Austin Diagnostic Clinic, Austin, Texas, sAllergy & Asthma Research Center Toledo, Ohio, and 6RhBne-Poulenc Rorer Pharmaceuticals Inc., Collegeville, Pennsylvania
ABSTRACT Triamcinolone acetonide (TAA) aerosol nasal inhaler has been shown to effectively relieve the symptoms of seasonal allergic rhinitis in adults and adolescents. We conducted a study to evaluate the efficacy and safety of once-daily administration of TAA aerosol nasal inhaler in pediatric patients aged 6 to 11 years with grass seasonal allergic rhinitis. This multicenter, randomized, double-blind, placebocontrolled, parallel-group study enrolled 116 children who were treated with either TAA aerosol nasal inhaler (220 kg/d) or placebo once daily for 2 weeks. Patients evaluated the severity of rhinitis symptoms (nasal stuffiness, discharge, sneezing, and itching) daily according to a four-
0149-2918/96/$3.50
point scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). Patients’ and physicians’ global evaluations of overall treatment efficacy were assessed at the end of the 2-week treatment period. Patients treated with TAA aerosol nasal inhaler had significantly greater reductions in all nasal symptom scores overall and in virtually all symptoms at the end of week 1 and week 2 compared with those in the placebo group. Both patients’ and physicians’ global evaluations of efficacy favored TAA aerosol nasal inhaler over placebo. This study demonstrated that once-daily administration of 220 pg of TAA aerosol nasal inhaler was well tolerated and effectively reduced the symptoms of seasonal allergic rhinitis in pediatric patients.
265
CLINICAL THERAPEUTICS”
INTRODUCTION Intranasal corticosteroids are highly effective in relieving the symptoms associated with both seasonal and perennial allergic rhinitis. 1A Additionally, topical formulations of synthetic corticosteroids have considerably reduced the systemic side effects and potential effects on adrenocortical function associated with systemic corticosteroid use.3,4 Triamcinolone acetonide (TAA) aerosol nasal inhaler,* the first intranasal corticosteroid approved in the United States for once-daily administration, has been shown to effectively reduce symptoms of seasonal and perennial allergic rhinitis with no measurable systemic effects, limited adverse events, and no measurable effects on adrenocortical function.5-11 The recommended starting dose for patients 12 years of age and older is 220 l.i,g/d. If adequate control is not achieved, the dose can be increased to a maximum of 440 kg/d. Once symptoms are controlled, some patients can be effectively maintained on 110 l,r,g/d.Although several studies have examined the safety and effectiveness of TAA aerosol nasal inhaler in populations that included young children with perennial allergic rhinitis” and adolescents with seasonal and perennial allergic rhinitis,“8,10 none specifically targeted seasonal allergic rhinitis symptoms with a once-daily, 220-pg TAA aerosol nasal inhaler dosing regimen in patients younger than age 12 years. Our study was designed to determine whether symptoms of seasonal allergic rhinitis in a pediatric population can be safely and effectively
*Trademark: Nasacort@ (RhBne-Poulenc Rorer Pharmaceuticals Inc., Collegeville, Pennsylvania).
266
reduced with once-daily administration 220 pg of TAA aerosol nasal inhaler.
PATIENTS
of
AND METHODS
Boys and premenarcheal girls aged 6 to 11 years with a l-year history of seasonal allergic rhinitis, a positive response to a skin prick test for grass allergens, and a minimum qualifying total rhinitis symptom (nasal stuffiness, nasal discharge, sneezing, and nasal itching) score of 24 points (out of a possible 48 points) were enrolled in the study. Patients were excluded for any clinically relevant deviation from normal medical or laboratory values, nasal candidiasis, acute sinusitis, or a history of hypersensitivity to corticosteroids. Patients also were excluded if they had been treated with nasal, inhaled, or systemic corticosteroids within 42 days of study enrollment; nasal cromolyn sodium within 14 days; an investigational drug within 90 days; or a medication that might produce or relieve the signs and symptoms of allergic rhinitis. Patients who had begun immunotherapy within 30 days of study enrollment or had participated in any previous TAA aerosol nasal inhaler study were excluded. The investigational protocol was approved by an institutional review board at each study site, and informed, written consent was obtained from each parent or guardian. This multicenter (five US centers), randomized, double-blind, placebo-controlled, parallel-group study was designed to compare the efficacy and safety of oncedaily administration of 220 p,g of TAA aerosol nasal inhaler with that of placebo in pediatric patients with grass seasonal allergic rhinitis. The study consisted of a screening/baseline peTiod fol-
C.H. BANOV ET AL.
lowed by a 2-week treatment period. The study was conducted during the grass pollen season, between the months of April and July. During the initial screening visit (5 to 14 days before randomization), the patient’s medical and drug history were recorded; a skin prick test, physical examination, and laboratory tests were performed; and mucous membranes were examined for signs of fungal infection. Diary cards were distributed to record daily nasal symptom scores (stuffiness, discharge, sneezing, and itching), concomitant medications, adverse events, and compliance with the prescribed study medication regimen. The severity of daily rhinitis symptoms was rated according to the following four-point scale: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. Symptoms were rated once daily in the evening and reflected symptom severity over the previous 24 hours. If the aggregate sum of the rhinitis symptom scores for 4 days preceding randomization was 24 points or more (out of a possible 48 points), the patient was randomized to one of two treatment groups. Patients received either 220 pg of TAA aerosol nasal inhaler (55 pg per puff) or placebo administered as 2 puffs in each nostril every morning for 14 days. New diary cards were distributed at this baseline visit and at the end of week 1; diaries were collected and reviewed after week 1 and at the final visit after the 2-week treatment period. At the final visit, medical and laboratory examinations were performed and global evaluations of treatment efficacy were recorded by the patient and the investigator according to the following scale: 0 = greatly improved, 1 = somewhat improved, 2 = no change, 3 = somewhat worsened, and 4 = greatly worsened.
Statistical Analyses The primary efficacy variables evaluated for this study were the mean changes from baseline in the daily symptom ratings for nasal stufftness, nasal discharge, sneezing, and the nasal index (the sum of these three symptom scores). Mean changes from baseline were averaged for each week separately and for the entire 2-week treatment period. Secondary efficacy variables included nasal itching and patients’ and investigators’ global evaluations of overall efficacy. The statistical model was a twoway analysis of variance with treatment and investigator as main effects and no interaction term. Differences between treatment groups were analyzed using a onesided t test. Statistical significance was set at an alpha level of 0.05.
RESULTS One hundred sixteen patients, 74 boys and 42 girls, were enrolled in the study. Fiftyeight patients were included in each treatment group; 65% and 62% of patients in the TAA aerosol nasal inhaler and placebo groups, respectively, were boys. Demographic characteristics were similar for both groups. Overall, the mean age was 9 years (range, 6 to 1 I years), with 93% of the study population white and 7% black. One hundred fifteen of the 116 patients completed the 2-week treatment period. One patient in the placebo group discontinued treatment after 8 days because the medication canister was empty despite using the medication as prescribed. One hundred fourteen of the 116 patients enrolled had evaluable data and were included in the efficacy analyses; results from the intent-totreat analyses did not differ from those obtained in the assessable population.
267
CLINICAL THERAPEUTICS”
Table I. Mean baseline rhinitis symptom scores.*
Symptom Nasal stuffiness Nasal discharge Sneezing Nasal index? Nasal itching
TAA Aerosol Nasal Inhaler (n = 58)
Placebo (n = 56)
Total (n = 114+)
2.19 2.05 1.92 6.16 2.06
2.19 1.83 1.83 5.85 2.07
2.19 1.94 1.88 6.01 2.07
TAA = triamcinolone acetonide. ‘Rhinitis symptom scale: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. +n = number of patients with evaluable data. ‘Nasal index is the sum of symptom scores for nasal stuffiness, nasal discharge,
Efficacy Mean nasal symptom ratings at baseline were similar for the two treatment groups and considered moderate in intensity, with values ranging from 1.83 to 2.19 for nasal stuffiness, nasal discharge, sneezing, and nasal itching (Table I). After 2 weeks of treatment, patients using TAA aerosol nasal inhaler showed statistically significant reductions (P c 0.05) from baseline in nasal stuffiness, nasal discharge, sneezing, nasal index, and nasal itching compared with the placebo group (Table II). The TAA aerosol nasal inhaler group also had significantly greater improvements (P c 0.05) in symptoms during week 1 and week 2 for nasal stuffiness, nasal discharge, nasal index, and nasal itching. Significant improvement (P < 0.05) also was observed during week 2 for sneezing. Daily mean changes from baseline over the 2-week treatment period also were examined for nasal index scores (figure). Beginning at day 2 and continuing throughout the 2-week treatment period,
268
and sneezing.
TAA aerosol nasal inhaler produced progressively larger reductions in nasal index scores compared with placebo. Both patients’ and physicians’ global evaluations of treatment efficacy significantly favored TAA aerosol nasal inhaler over placebo (P < 0.05). Eighty-six percent of patients (50 of 58) treated with TAA aerosol nasal inhaler reported that their nasal symptoms had greatly or somewhat improved compared with 64% of those (36 of 56) in the placebo group. In addition, more physicians reported that patients treated with TAA aerosol nasal inhaler had greatly or somewhat improved symptoms compared with those receiving placebo (72% vs 64%, respectively).
Safety Safety was evaluated for all 116 patients enrolled in the study. No serious adverse events were reported during the study, nor did any patient discontinue treatment because of an adverse event. Thirty-one patients in the TAA aerosol nasal inhaler group and 22 patients in the
C.H. BANOV ET AL.
Table II. Adjusted* changes from baseline in allergic rhinitis symptoms+ in assessable patients over the 2-week treatment period. Values are given as mean + SE. TAA Aerosol Nasal Inhaler” Week 1 (n = 58) Week 2 (n = 57)
Symptom Nasal stuffiness Week 1 Week 2 Overall Nasal discharge Week 1 Week 2 Overall Sneezing Week 1 Week 2 Overall Nasal index” Week
1
Placebos Week 1 (n = 56)
Overall (n = 58)
Week 2 (n = 54) Overall (n = 56)
-060+008”
-0.33
f 0.08
-0:91
+ 0:10n
-0.37
f 0.10
-0.74
r 0.08”
-0.34
r 0.08
-0.67
f 0.095
-0.38
+ 0.09
-1.02
2 0.10”
-0.46
f 0.11
-0.84
f 0.09$
-0.42
f 0.09
-0.57
+ 0.10
-0.34
f 0.10
-0.89
f 0.10”
-0.46
f 0.10
-0.72
zt 0.09”
-0.40
+ 0.10 f 0.20
-I .85 + 0.20”
-1.05
Week 2
-2.82
f 0.24”
-1.30
+ 0.24
Overall
-2.30
+ 0.20”
-1.16
-I- 0.21
Nasal
itching
-0.64 f 0.10”
-0.37
f 0.10
Week 2
-0.95
+ 0.11s
-0.53
+ 0.11
Overall
-0.76
f 0.10”
-0.43
* 0.10
Week
1
TAA = triamcinolone acetonide. *Means adjusted for imbalances among investigators. +Rhinitis symptom scale: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. ‘n = number of patients with evaluable data. “P < 0.05 versus placebo for one-tailed t test. “Nasal index is the sum of symptom scores for nasal stuffiness, nasal discharge,
placebo group reported adverse events; the majority of these events were mild. The most frequently reported adverse events were headache and epistaxis, with both occurring more often in the TAA aerosol nasal inhaler group than in the placebo group. Adverse events indicative of topical effects were minimal and similar for both treatment groups. No fungal infections were detected at baseline or the
and sneezing.
conclusion of the study. No clinically significant changes from baseline in vital signs or laboratory values were observed in either treatment group.
DISCUSSION
AND CONCLUSION
TAA aerosol nasal inhaler is effective and well tolerated by adults and adolescents with symptoms of seasonal or perennial
269
CLINICAL THERAPEUTICS”
0 Placebo 0 TAA aerosol nasal inhaler (220 @d)
E 3
‘-
-1
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I
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/
I
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1
2
3
4
5
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Study Day
Figure.
Daily mean changes (GE) from baseline in the nasal index over the 2-week treatment period. The nasal index is the sum of the symptom scores for nasal stuffiness, nasal discharge, and sneezing. TAA = triamcinolone acetonide.
allergic rhinitis5-to and by children as young as age 4 years with symptoms of perennial allergic rhinitis.” Our study confirms and reinforces the efficacy and safety of once-daily administration of TAA aerosol nasal inhaler in children aged 6 to 11 years to relieve symptoms of seasonal allergic rhinitis. Patients treated with TAA aerosol nasal inhaler had significantly greater reductions (P < 0.05) in all nasal symptom scores after 2 weeks of treatment compared with those receiving placebo. Virtually all nasal symptoms were significantly reduced (P < 0.05) at the end of weeks 1 and 2 in patients treated with TAA aerosol nasal inhaler. Both patients and physicians
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reported TAA aerosol nasal inhaler to be more favorable than placebo in controlling rhinitis symptoms. Although patients in the TAA aerosol nasal inhaler group in this study reported a higher percentage of adverse events than those in the placebo group, overall findings from other studies of pediatric patients show comparable adverse events between active treatment groups and placebo and no apparent dose-related trends in studies with varying TAA aerosol nasal inhaler dosages.6~8~10*”In addition, other studies8~i0~” have shown that epistaxis is reported more frequently or comparably in patients receiving placebo compared with those treated with TAA aerosol
C.H. BANOV ET AL.
nasal inhaler. While patients treated with TAA aerosol nasal inhaler in our study had a somewhat higher incidence of epistaxis compared with those in the placebo group, these data may be skewed because recurrent epistaxis is especially common in pediatric patients.” Control of seasonal allergic rhinitis symptoms was accomplished with oncedaily administration of medication. Although this is an important consideration with all patients in that multiple daily dosing is associated with patient noncompliance and incomplete therapeutic response, it is especially important when treating children.13,14 From our findings, we concluded that once-daily administration of 220 p,g of TAA aerosol nasal inhaler is a reliable and effective treatment for the symptoms of seasonal allergic rhinitis and is well tolerated by pediatric patients.
ACKNOWLEDGMENT This study was funded in part by RhonePoulenc Rorer Pharmaceuticals Inc., Collegeville, Pennsylvania.
Address correspondence to: Charles H. Banov, MD, 9213A University Boulevard, North Charleston, SC 29406.
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