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Fluticasone Propionate Nasal Spray in an Anatomical Model of the Human Nasal Cavity
AB218 Abstracts
704
Once-Daily Treatment with Beclomethasone Dipropionate Nasal Aerosol Is Effective in Improving Total Nasal Symptom Scores (TNSS) in Children with Perennial Allergic Rhinitis (PAR) Regardless of Baseline Symptom Severity Niran J. Amar, MD, FAAAAI1, William E. Berger, MD, MBA, FAAAAI2, Robert L. Jacobs, MD3, Calvin Small, MD, MS4; 1Allergy Asthma Research Institute, Waco, TX, 2Allergy & Asthma Associates of Southern California, Mission Viejo, CA, 3Biogenics Research Institute, San Antonio, TX, 4Teva Branded Pharmaceutical Products R&D, Inc. RATIONALE: Beclomethasone dipropionate (BDP) nasal aerosol (a nonaqueous formulation) is approved for management of seasonal and perennial allergic rhinitis in adolescents and adults. This post hoc analysis evaluated the effectiveness of BDP nasal aerosol based on baseline symptom severity in children with PAR. METHODS: This 12-week, double-blind, placebo-controlled study evaluated children with PAR (aged 4-11 years) randomized to BDP nasal aerosol 80mg/day; n5362) or placebo (n5185). Efficacy assessments included change from baseline in patient-reported average AM and PM reflective and instantaneous TNSS (rTNSS and iTNSS) over 6 weeks for children aged 6-11 years (primary variable) evaluated by baseline symptom severity: less severe (baseline rTNSS or iTNSS RESULTS: Treatment with BDP nasal aerosol improved average AM and PM rTNSS versus placebo in children with more severe baseline symptoms (least squares mean [95% confidence interval] difference: 20.70 [21.31, 20.08]; P50.027) and less severe baseline symptoms (20.64 [21.20, 20.08]; P50.026) over the 6 weeks. Treatment with BDP nasal aerosol improved average AM/PM iTNSS versus placebo in children with more severe baseline symptoms (20.72 [21.32, 20.12]; P50.019); however, in children with less severe baseline symptoms, the improvement did not reach statistical significance (80mg 20.43 [20.92, 0.07]; P50.094). CONCLUSIONS: In this post hoc analysis, BDP nasal aerosol treatment in children with PAR resulted in significant improvements versus placebo in rTNSS regardless of baseline symptom severity and in iTNSS in the group with more severe symptoms at baseline. Study sponsored by Teva.
MONDAY
705
Cetirizine Improves Both Ocular and Nasal Allergy Symptoms in Subjects with Perennial Allergic Rhinitis Eduardo Urdaneta, MD1, Qiong Du, MS2, Mei-Miau Wu, Dr PH3, Kathleen B. Franklin, BSN, RN1, Mitesh Patel, PharmD1; 1McNeil Consumer Healthcare, Fort Washington, PA, 2Johnson & Johnson Consumer Products, China, Shanghai, China, 3J & J Consumer Products, US, Morris Plains, NJ. RATIONALE: Evaluate efficacy of cetirizine 5 to 20mg for ocular and nasal allergy symptom relief in subjects with perennial allergic rhinitis (PAR). METHODS: A post hoc evaluation of four randomized PAR studies of _12 years was cetirizine 5 to 20mg administered to subjects aged > conducted. Total ocular symptom score (TOSS) was sum of severity scores for itchy eyes and watery eyes. Total nasal symptom score (TNSS) was sum of severity scores for sneezing, runny nose, itchy nose, and postnasal drip. Individual symptom scores were rated on 4-point scale (05none to 35severe). TOSS and TNSS changes over a 4-week treatment period, by day in first week, and weekly were evaluated in subjects with _1, _1 and itchy nose symptom score > baseline itchy eye symptom score > respectively. RESULTS: In the cetirizine groups, TOSS (N5416) improved 32.8% to 68.3% from baseline and TNSS (N5444) improved 30.9% to 53.9% from baseline over 4 weeks (adjusted mean changes of -1.1 to -2.2, respectively for TOSS and -2.3 to -4.0 respectively for TNSS). Compared with placebo (TOSS, N5311, TNSS, N5323, respectively), improvements with cetirizine were statistically superior (P<0.05) for TOSS in 4 of 6 groups and for TNSS in all 6 groups over 4 weeks (95% CI for between-treatment differences ranging from: [-1.02, -0.30] to [-0.69, 0.16] and [-1.96,-0.59] to [-1.58, -0.10], respectively). In the 6 cetirizine groups, treatment effect size
J ALLERGY CLIN IMMUNOL FEBRUARY 2015
ranged from 0.24 to 0.61 for ocular symptoms and from 0.33 to 0.62 for nasal symptoms. CONCLUSIONS: Cetirizine improves both ocular and nasal allergy symptoms in subjects with PAR.
706
Quantification of the Distribution of Azelastine HCl/ Fluticasone Propionate Nasal Spray in an Anatomical Model of the Human Nasal Cavity Alexander D’Addio, PhD1, Nancy Ruiz, MD1, Michael Mayer, PhD2, William E. Berger, MD, MBA, FAAAAI3, Eli O. Meltzer, MD, FAAAAI4; 1 Meda Pharmaceuticals, Somerset, NJ, 2Next Breath, LLC, 3Allergy & Asthma Associates of Southern California, Mission Viejo, CA, 4Allergy and Asthma Medical Group & Research Center, San Diego, CA. RATIONALE: In vitro evaluations using an anatomical model of the human nasal cavity quantified the distribution of azelastine HCl (AZ) and fluticasone propionate (FP) in a single nasal spray (Dymista) compared to sequential sprays of marketed azelastine (Astelin) and either Flonase or generic fluticasone. METHODS: The cast was divided into 4 sections from anterior to posterior of the cast. A single spray of AZ/FP (0.137 mL [137 mcg of azelastine/50 mcg of fluticasone propionate]) or sequential single sprays of azelastine (0.137 mL) followed by generic fluticasone propionate or Flonase nasal spray (0.100 mL) were manually actuated into the model. A vacuum (15 mL/min) was applied during actuation to simulate nasal inhalation. Following extraction from the nasal cast, HPLC was used to quantify drug deposition on the different sections of the cast. Each experiment was repeated three times. RESULTS: A single spray of AZ/FP showed a uniform distribution of close to 100% of applied drug within the nose/nasal valve and turbinates (first 2 sections of the cast); the average % AZ was 61.4% in section 1 and 38.6% in section 2 and the average % FP was 65.4% and 34.6% in sections 1 and 2, respectively. In comparison, single sprays of the individual agents showed uneven distribution of AZ and FP and a substantial amount of dripping from sequential administration. CONCLUSIONS: Application of AZ/FP in a single spray provided more uniform distribution and greater retention in the nasal cavity than sequential sprays of the individual components, potentially allowing for better local absorption of medication.
704
Once-Daily Treatment with Beclomethasone Dipropionate Nasal Aerosol Is Effective in Improving Total Nasal Symptom Scores (TNSS) in Children with Perennial Allergic Rhinitis (PAR) Regardless of Baseline Symptom Severity Niran J. Amar, MD, FAAAAI1, William E. Berger, MD, MBA, FAAAAI2, Robert L. Jacobs, MD3, Calvin Small, MD, MS4; 1Allergy Asthma Research Institute, Waco, TX, 2Allergy & Asthma Associates of Southern California, Mission Viejo, CA, 3Biogenics Research Institute, San Antonio, TX, 4Teva Branded Pharmaceutical Products R&D, Inc. RATIONALE: Beclomethasone dipropionate (BDP) nasal aerosol (a nonaqueous formulation) is approved for management of seasonal and perennial allergic rhinitis in adolescents and adults. This post hoc analysis evaluated the effectiveness of BDP nasal aerosol based on baseline symptom severity in children with PAR. METHODS: This 12-week, double-blind, placebo-controlled study evaluated children with PAR (aged 4-11 years) randomized to BDP nasal aerosol 80mg/day; n5362) or placebo (n5185). Efficacy assessments included change from baseline in patient-reported average AM and PM reflective and instantaneous TNSS (rTNSS and iTNSS) over 6 weeks for children aged 6-11 years (primary variable) evaluated by baseline symptom severity: less severe (baseline rTNSS or iTNSS
MONDAY
705
Cetirizine Improves Both Ocular and Nasal Allergy Symptoms in Subjects with Perennial Allergic Rhinitis Eduardo Urdaneta, MD1, Qiong Du, MS2, Mei-Miau Wu, Dr PH3, Kathleen B. Franklin, BSN, RN1, Mitesh Patel, PharmD1; 1McNeil Consumer Healthcare, Fort Washington, PA, 2Johnson & Johnson Consumer Products, China, Shanghai, China, 3J & J Consumer Products, US, Morris Plains, NJ. RATIONALE: Evaluate efficacy of cetirizine 5 to 20mg for ocular and nasal allergy symptom relief in subjects with perennial allergic rhinitis (PAR). METHODS: A post hoc evaluation of four randomized PAR studies of _12 years was cetirizine 5 to 20mg administered to subjects aged > conducted. Total ocular symptom score (TOSS) was sum of severity scores for itchy eyes and watery eyes. Total nasal symptom score (TNSS) was sum of severity scores for sneezing, runny nose, itchy nose, and postnasal drip. Individual symptom scores were rated on 4-point scale (05none to 35severe). TOSS and TNSS changes over a 4-week treatment period, by day in first week, and weekly were evaluated in subjects with _1, _1 and itchy nose symptom score > baseline itchy eye symptom score > respectively. RESULTS: In the cetirizine groups, TOSS (N5416) improved 32.8% to 68.3% from baseline and TNSS (N5444) improved 30.9% to 53.9% from baseline over 4 weeks (adjusted mean changes of -1.1 to -2.2, respectively for TOSS and -2.3 to -4.0 respectively for TNSS). Compared with placebo (TOSS, N5311, TNSS, N5323, respectively), improvements with cetirizine were statistically superior (P<0.05) for TOSS in 4 of 6 groups and for TNSS in all 6 groups over 4 weeks (95% CI for between-treatment differences ranging from: [-1.02, -0.30] to [-0.69, 0.16] and [-1.96,-0.59] to [-1.58, -0.10], respectively). In the 6 cetirizine groups, treatment effect size
J ALLERGY CLIN IMMUNOL FEBRUARY 2015
ranged from 0.24 to 0.61 for ocular symptoms and from 0.33 to 0.62 for nasal symptoms. CONCLUSIONS: Cetirizine improves both ocular and nasal allergy symptoms in subjects with PAR.
706
Quantification of the Distribution of Azelastine HCl/ Fluticasone Propionate Nasal Spray in an Anatomical Model of the Human Nasal Cavity Alexander D’Addio, PhD1, Nancy Ruiz, MD1, Michael Mayer, PhD2, William E. Berger, MD, MBA, FAAAAI3, Eli O. Meltzer, MD, FAAAAI4; 1 Meda Pharmaceuticals, Somerset, NJ, 2Next Breath, LLC, 3Allergy & Asthma Associates of Southern California, Mission Viejo, CA, 4Allergy and Asthma Medical Group & Research Center, San Diego, CA. RATIONALE: In vitro evaluations using an anatomical model of the human nasal cavity quantified the distribution of azelastine HCl (AZ) and fluticasone propionate (FP) in a single nasal spray (Dymista) compared to sequential sprays of marketed azelastine (Astelin) and either Flonase or generic fluticasone. METHODS: The cast was divided into 4 sections from anterior to posterior of the cast. A single spray of AZ/FP (0.137 mL [137 mcg of azelastine/50 mcg of fluticasone propionate]) or sequential single sprays of azelastine (0.137 mL) followed by generic fluticasone propionate or Flonase nasal spray (0.100 mL) were manually actuated into the model. A vacuum (15 mL/min) was applied during actuation to simulate nasal inhalation. Following extraction from the nasal cast, HPLC was used to quantify drug deposition on the different sections of the cast. Each experiment was repeated three times. RESULTS: A single spray of AZ/FP showed a uniform distribution of close to 100% of applied drug within the nose/nasal valve and turbinates (first 2 sections of the cast); the average % AZ was 61.4% in section 1 and 38.6% in section 2 and the average % FP was 65.4% and 34.6% in sections 1 and 2, respectively. In comparison, single sprays of the individual agents showed uneven distribution of AZ and FP and a substantial amount of dripping from sequential administration. CONCLUSIONS: Application of AZ/FP in a single spray provided more uniform distribution and greater retention in the nasal cavity than sequential sprays of the individual components, potentially allowing for better local absorption of medication.