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1005 Evaluation of safety and efficacy of dexacort™ turbinaire® (DEX) nasal spray in patients with perennial allergic rhinitis
434 1005
Abstracts
J ALLERGY CLIN IMMUNOL JANUARY 1996
EVALUATION OF SAFETY AND EFFICACY OF DEXACORTTM TURBINAIRE~ (DEX) NASAL SPRAY IN PATIENTS WITH PERENNIAL ALLERGIC RHINITIS. G a r y Rachelefskv. MD. Jeffrey Adel~lass. MD. J o n a t h a n Corren. MD. Sheldon Snector. M D . H o w a r d Schanker. MD. Linda Kielv. Sheldon Siegel, MD, Los Angeles, CA and Dallas, Texas.This randomized, double-blind, placebo-controlled trial was performed to assess the safety and efficacy of DexacorffM Turbinaire~fDEX) nasal spray in adult patients with perennial allergic rhinitis. 73 mite-allergic patients received either DEX 200 m e g BID, D E X 200 m e g TID, placebo BID or placebo TID for 12 weeks. Nasal symptoms were assessed daily and A M e o r t i s o l / A C T H stimulation testing was performed at baseline, 4 and 12 weeks. After 4 weeks of treatment, nasal symptoms improved in patients treated with both doses o f D E X and placebo. A f t e r 12 weeks, both doses o f D E X r e d u c e d sneezing (13=.02) and nasal c o n g e s t i o n (p---O.03) c o m p a r e d with placebo. There was no difference between the two doses of D E X after 4 or 12 weeks of treatment. A M cortisol levels declined after 4 and 12 weeks in patients treated with DEX c o m p a r e d with placebo, although these changes were of small magnitude. Responses to A C T H stimulation did not differ between D E X and placebo or between the two doses o f D E X at 4 or 12 weeks. In conclusion, D E X n a s a l spray appears to be effective while eansing minimal changes in adrenal function in most patients when administered for 12 weeks.
1006 Comparative CNS Depressant Effects Cetir,zine and Classical Antihistamines an Experimental Animal Model.
of in
M del Prado MS. J Sherwood MS. JA Hey PhD. Kenilworth NJ Sedation is the most common side effect of first generation H 1 antihistamines. The second generation H 1 antihistamines, Ioratadine and terfenadine are representative of therapeutically effective antihistamines devoid of sedative side effects. In the present study, the CNS effect profile of several sedating antihistamines and the newly developed second generation antihistamine, certirizine were evaluated using cortical EEG in anesthetized guinea pigs. The goal of the study was to determine the relationship between the dose producing depression of cortical EEG (CNS effect) and dose producing peripheral H1 antihistamine activity (H 1 antihistamine ED50). The lowest dose of diphenhydramine and promethazine that depressed cortical EEG activity was 0.1 and 0.03 mg/kg, i.v., respectively. The EEG depression/H 1 antihistamine ratio for diphenhydramine and promethazine was 0.6 and 2.0, indicating greater sedative activity of these drugs. The lowest dose of cetirizine producing depression of EEG was 3.0 mg/kg, i.v. The maximal depressant activity seen at this dose was a decrease in EEG amplitude of 21%. The separation between the EEG depression and the peripheral antihistamine doses was 33 fold for cetirizine. In contrast, the nonsedating antihistamine, Ioratadine did not depress cortical EEG at doses up to 100 mg/Ikg, and its separation between CNS and antihistamine activities was - 170. These findings indicate that cetirizine is mildly depressant and exhibits a sedative potential that is less than diphenhydramine or promethazine. In conclusion, we found that the relative CNS depressant liability of H 1 antihistamines based on a separation of antihistamine activity and depression of cortical EEG activity in the anesthetized guinea pig is diphenhydramine = promethazine > cetirizine ~ Ioratadine = placebo.
1007 Onset of Action, Efficacy and Safety of a Single Dose of 60 mg and 120 mg Fexofenadine HCI for Ragweed ( R W ) Allergy Using C o n t r o l l e d A n t i g e n E x p o s u r e in an Environmental Exposure Unit (EEU), JH Day
MD~ MP Briseoe MD~ A Welsh BSc~ J Smith BScH~ J Mason R N MN, K i n g s t o n , Ontario, Canada. One hundred and forty-six RW sensitive subjects were primed in the offseason with RW pollen in the EEU. One hundred and thirtysix subjects who adequately responded to 5000 gr/cu m in the EEU entered a single dose placebo phase. On the test day, the 99 subjects who qualified for the study were given a single dose of double blind medication either Fexofenadine HCI 120 mg (33), 60 mg (33) or placebo (33) after 60 min of RW exposure when all were sufficiently symptomatic. RW pollen exposure continued over 5 hrs and subjects recorded symptoms every 20 rain. Median time to clinically important relief(CIR) was 60 rain for both Fexofenadine HCI treatment groups (p=0.018) and 100 min for placebo. The proportion having CIR was 82% at 60 rag, 85% at 120 nag and 64% for placebo. The treated groups had a reduction in total symptom score double that of the placebo, i.e. 30% and 28% respectively for 60 mg and 120 mg ofFexofenadine HCI versus 14% for placebo. Both doses had comparable efficacy. Fexofenadine HCI is safe and well tolerated at single doses of 60 mg and 120 mg and average time to onset of effect was 60 rain using controlled pollen exposure in the EEU setting.
1008 A Placebo-Controlled Trial of Cetirizine in Seasonal Allergic R h i n i t i s in C h i l d r e n Aged 6 to 11. W R Lumry MD, DS Pearlman MD, Dallas, TX, Aurora, CO. Cetirizine, a highly selective HI-antagonist, has been shown to be efficacious in the treatment of seasonal allergic rhinitis (SAR), perennial allergic rhinitis and chronic urticaria when given oncedaily. In the present 4-week, randomized, double-blind, and placebocontrolled study, the safety and efficacy of cetirizine syrup (5 or 10 mg daily) were investigated in 209 children aged 6 to I l years with SAR. Patients, with the assistance of a parent, recorded severity of symptoms (sneezing, nasal discharge, itchy eyes, itchy nose or mouth, conjunctivitis and nasal congestion) twice daily on diary cards using a rating scale from 0 (none) to 3 (severe). A total symptom severity score (TSS) was derived from all symptoms excluding nasal congestion. TSS at baseline was comparable for the three treatment groups, ranging from 6.8 to 7.0. Cetirizine 10 mg given once-daily produced a mean redaction in TSS by 3.2 over the four week treatment period (1)<0.05). Cetirizine 5 mg given once-daily produced a mean reduction in TSS by 2.4 however this difference was not statistically different from placebo. Cetirizine l0 mg daily produced a mean reduction in symptom scores by 2.5, 3.2, 3.5 and 3.5 compared to baseline at weeks 1 to 4. Furthermore, cetirizine l0 mg significantly improved the symptoms of itchy eyes and itchy nose or mouth. The most commonly reported adverse reactions were headache, pharyngitis and abdominal pain which were not statistically different from placebo. Once-daily Cetirizine is safe in the treatment of SAR in children aged 6 to 11 years. Cetirizine 10rag provides effective improvement in symptoms associated with SAR.
Abstracts
J ALLERGY CLIN IMMUNOL JANUARY 1996
EVALUATION OF SAFETY AND EFFICACY OF DEXACORTTM TURBINAIRE~ (DEX) NASAL SPRAY IN PATIENTS WITH PERENNIAL ALLERGIC RHINITIS. G a r y Rachelefskv. MD. Jeffrey Adel~lass. MD. J o n a t h a n Corren. MD. Sheldon Snector. M D . H o w a r d Schanker. MD. Linda Kielv. Sheldon Siegel, MD, Los Angeles, CA and Dallas, Texas.This randomized, double-blind, placebo-controlled trial was performed to assess the safety and efficacy of DexacorffM Turbinaire~fDEX) nasal spray in adult patients with perennial allergic rhinitis. 73 mite-allergic patients received either DEX 200 m e g BID, D E X 200 m e g TID, placebo BID or placebo TID for 12 weeks. Nasal symptoms were assessed daily and A M e o r t i s o l / A C T H stimulation testing was performed at baseline, 4 and 12 weeks. After 4 weeks of treatment, nasal symptoms improved in patients treated with both doses o f D E X and placebo. A f t e r 12 weeks, both doses o f D E X r e d u c e d sneezing (13=.02) and nasal c o n g e s t i o n (p---O.03) c o m p a r e d with placebo. There was no difference between the two doses of D E X after 4 or 12 weeks of treatment. A M cortisol levels declined after 4 and 12 weeks in patients treated with DEX c o m p a r e d with placebo, although these changes were of small magnitude. Responses to A C T H stimulation did not differ between D E X and placebo or between the two doses o f D E X at 4 or 12 weeks. In conclusion, D E X n a s a l spray appears to be effective while eansing minimal changes in adrenal function in most patients when administered for 12 weeks.
1006 Comparative CNS Depressant Effects Cetir,zine and Classical Antihistamines an Experimental Animal Model.
of in
M del Prado MS. J Sherwood MS. JA Hey PhD. Kenilworth NJ Sedation is the most common side effect of first generation H 1 antihistamines. The second generation H 1 antihistamines, Ioratadine and terfenadine are representative of therapeutically effective antihistamines devoid of sedative side effects. In the present study, the CNS effect profile of several sedating antihistamines and the newly developed second generation antihistamine, certirizine were evaluated using cortical EEG in anesthetized guinea pigs. The goal of the study was to determine the relationship between the dose producing depression of cortical EEG (CNS effect) and dose producing peripheral H1 antihistamine activity (H 1 antihistamine ED50). The lowest dose of diphenhydramine and promethazine that depressed cortical EEG activity was 0.1 and 0.03 mg/kg, i.v., respectively. The EEG depression/H 1 antihistamine ratio for diphenhydramine and promethazine was 0.6 and 2.0, indicating greater sedative activity of these drugs. The lowest dose of cetirizine producing depression of EEG was 3.0 mg/kg, i.v. The maximal depressant activity seen at this dose was a decrease in EEG amplitude of 21%. The separation between the EEG depression and the peripheral antihistamine doses was 33 fold for cetirizine. In contrast, the nonsedating antihistamine, Ioratadine did not depress cortical EEG at doses up to 100 mg/Ikg, and its separation between CNS and antihistamine activities was - 170. These findings indicate that cetirizine is mildly depressant and exhibits a sedative potential that is less than diphenhydramine or promethazine. In conclusion, we found that the relative CNS depressant liability of H 1 antihistamines based on a separation of antihistamine activity and depression of cortical EEG activity in the anesthetized guinea pig is diphenhydramine = promethazine > cetirizine ~ Ioratadine = placebo.
1007 Onset of Action, Efficacy and Safety of a Single Dose of 60 mg and 120 mg Fexofenadine HCI for Ragweed ( R W ) Allergy Using C o n t r o l l e d A n t i g e n E x p o s u r e in an Environmental Exposure Unit (EEU), JH Day
MD~ MP Briseoe MD~ A Welsh BSc~ J Smith BScH~ J Mason R N MN, K i n g s t o n , Ontario, Canada. One hundred and forty-six RW sensitive subjects were primed in the offseason with RW pollen in the EEU. One hundred and thirtysix subjects who adequately responded to 5000 gr/cu m in the EEU entered a single dose placebo phase. On the test day, the 99 subjects who qualified for the study were given a single dose of double blind medication either Fexofenadine HCI 120 mg (33), 60 mg (33) or placebo (33) after 60 min of RW exposure when all were sufficiently symptomatic. RW pollen exposure continued over 5 hrs and subjects recorded symptoms every 20 rain. Median time to clinically important relief(CIR) was 60 rain for both Fexofenadine HCI treatment groups (p=0.018) and 100 min for placebo. The proportion having CIR was 82% at 60 rag, 85% at 120 nag and 64% for placebo. The treated groups had a reduction in total symptom score double that of the placebo, i.e. 30% and 28% respectively for 60 mg and 120 mg ofFexofenadine HCI versus 14% for placebo. Both doses had comparable efficacy. Fexofenadine HCI is safe and well tolerated at single doses of 60 mg and 120 mg and average time to onset of effect was 60 rain using controlled pollen exposure in the EEU setting.
1008 A Placebo-Controlled Trial of Cetirizine in Seasonal Allergic R h i n i t i s in C h i l d r e n Aged 6 to 11. W R Lumry MD, DS Pearlman MD, Dallas, TX, Aurora, CO. Cetirizine, a highly selective HI-antagonist, has been shown to be efficacious in the treatment of seasonal allergic rhinitis (SAR), perennial allergic rhinitis and chronic urticaria when given oncedaily. In the present 4-week, randomized, double-blind, and placebocontrolled study, the safety and efficacy of cetirizine syrup (5 or 10 mg daily) were investigated in 209 children aged 6 to I l years with SAR. Patients, with the assistance of a parent, recorded severity of symptoms (sneezing, nasal discharge, itchy eyes, itchy nose or mouth, conjunctivitis and nasal congestion) twice daily on diary cards using a rating scale from 0 (none) to 3 (severe). A total symptom severity score (TSS) was derived from all symptoms excluding nasal congestion. TSS at baseline was comparable for the three treatment groups, ranging from 6.8 to 7.0. Cetirizine 10 mg given once-daily produced a mean redaction in TSS by 3.2 over the four week treatment period (1)<0.05). Cetirizine 5 mg given once-daily produced a mean reduction in TSS by 2.4 however this difference was not statistically different from placebo. Cetirizine l0 mg daily produced a mean reduction in symptom scores by 2.5, 3.2, 3.5 and 3.5 compared to baseline at weeks 1 to 4. Furthermore, cetirizine l0 mg significantly improved the symptoms of itchy eyes and itchy nose or mouth. The most commonly reported adverse reactions were headache, pharyngitis and abdominal pain which were not statistically different from placebo. Once-daily Cetirizine is safe in the treatment of SAR in children aged 6 to 11 years. Cetirizine 10rag provides effective improvement in symptoms associated with SAR.