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Effectiveness of Ciclesonide Nasal Aerosol in Adult and Adolescent Patients With Seasonal Allergic Rhinitis (SAR)
BDP were epistaxis (14% vs 9%), headache (41% vs 39%), pharyngitis (28% vs 21%). CONCLUSIONS: One-year treatment with MFNS 100 mcg QD improved overall condition of PAR in children and was well-tolerated, with no evidence of HPA-axis suppression or ocular changes.
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Low Systemic Bioavailability of Ciclesonide Aqueous Nasal Spray and Ciclesonide HFA Nasal Aerosol Compared With Orally Inhaled Ciclesonide M. Weiswasser1, J. Zhu2, V. Chia1, R. Nave3, M. Wingertzahn1; 1 ALTANA Pharma US, A NYCOMED Company, Florham Park, NJ, 2 ALTANA Pharma US, A Nycomed Company, Florham Park, NJ, 3Altana Pharma AG, Konstanz, GERMANY. RATIONALE: This study investigated the pharmacokinetics of 2 ciclesonide formulations for allergic rhinitis, an aqueous nasal spray and a hydro-fluoro-alkane (HFA) nasal aerosol, compared with a solution formulation of ciclesonide for treatment of asthma focusing on desisobutyryl-ciclesonide (des-CIC), the pharmacologically active metabolite of ciclesonide. METHODS: Healthy volunteers ( 18 years; N 5 30) were randomized in an open-label, single-dose, 3-period crossover study to 300 mg ciclesonide aqueous nasal spray, 300 mg ciclesonide HFA nasal aerosol (ciclesonide-HFA), or 320 mg ciclesonide orally inhaled by a metered-dose inhaler (MDI). Primary pharmacokinetic parameters are area under the serum concentration time curve extrapolated to infinity (AUCinf) and maximum serum concentraton (Cmax) of des-CIC. The safety and tolerability of ciclesonide were also evaluated. RESULTS: Concentrations of des-CIC above 10 pg/mL (5 lower limit of quantification) were detected in only 3% of the serum samples in volunteers receiving ciclesonide aqueous. The highest value of des-CIC for this treatment was 26.7 pg/mL. Hence, bioavailability is too low to characterize pharmacokinetic properties accurately for this formulation. Mean Cmax (ng/L) of des-CIC for ciclesonide-HFA and orally inhaled ciclesonide were 59.1 and 586.2, respectively. Mean AUCinf of des-CIC for ciclesonide-HFA and for orally inhaled ciclesonide were 397.5 and 2,685 ngdh/L, respectively. The exposure of des-CIC following intranasal administration of HFA nasal is 14.3% compared to the inhalation using the same formulation via MDI. CONCLUSIONS: The systemic bioavailability of des-CIC was low for both nasal ciclesonide formulations compared with orally inhaled ciclesonide with that of aqueous nasal spray lower than that of HFA nasal aerosol.
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Effectiveness of Ciclesonide Nasal Aerosol in Adult and Adolescent Patients With Seasonal Allergic Rhinitis (SAR) J. van Bavel1, C. LaForce2, E. Meltzer3, V. Chia4, P. Darken4, M. Wingertzahn4; 1Allergy and Asthma Association, Austin, TX, 2University of North Carolina School of Medicine, Raleigh, NC, 3Allergy and Asthma Medical Group and Research Center, San Diego, CA, 4ALTANA Pharma US Inc, A Nycomed Company, Florham Park, NJ. RATIONALE: Corticosteroid aqueous nasal sprays are effective treatments for allergic rhinitis; however, aerosol-based nasal formulations are preferred by some patients. This dose-ranging study evaluated the effectiveness of a hydro-fluoro-alkane (HFA) nasal aerosol formulation of ciclesonide. METHODS: Adult and adolescent patients ( 12 years) with a history of SAR were randomized in a double-blind manner to receive ciclesonide HFA nasal aerosol 75 mg, 150 mg, or 300 mg or placebo once daily for up to 2 weeks. Efficacy was assessed by patient-reported average AM and PM reflective and instantaneous total nasal symptom scores (TNSS) and patient-reported AM instantaneous TNSS. The safety and tolerability of ciclesonide were also assessed. RESULTS: All ciclesonide HFA doses demonstrated a statistically significantly greater reduction from baseline in 24-hour reflective TNSS versus placebo (0.64 [p 5 0.011] for the75-mg group; 0.89 [p < 0.001] for 150-mg group; and 0.80 [p 5 0.001] for the 300-mg group versus placebo
on days 1 to 14]. Twenty-four hour average AM and PM instantaneous TNSS and patient-reported AM instantaneous TNSS were similar (p 0.003 for all groups versus placebo). The incidence of treatment-related adverse events was low (< 1.6% for all) and was similar among all treatment groups. CONCLUSIONS: The HFA nasal aerosol formulation of ciclesonide demonstrated statistically significant reduction in 24-hour TNSS versus placebo. Ciclesonide HFA is appropriate for further clinical phase 3 investigation.
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Once-daily Fluticasone Furoate Nasal Spray Showed Greater Improvement In Nocturnal Quality Of Life In Subjects With Seasonal Allergic Rhinitis Compared With Oral Fexofenadine C. P. Andrews1, B. G. Martin2, R. L. Jacobs3, J. Diaz4, W. T. Toler5, B. A. Prillaman5, A. A. Dalal5, E. E. Philpot5; 1Diagnostics Research Group, San Antonio, TX, 2Southwest Allergy and Asthma Research, San Antonio, TX, 3Biogenics Research Institute, San Antonio, TX, 4 Allergy, Asthma and Immunology Associates of South Texas, San Antonio, TX, 5GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: Fluticasone Furoate Nasal Spray (FFNS), a new enhancedaffinity intranasal corticosteroid, was evaluated against oral fexofenadine (FEX) using the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) to further characterize its therapeutic profile. METHODS: This was a randomized, double-blind, double-dummy, placebo-controlled, 2-week study (FFU109045) of 936 subjects with SAR who received either FFNS 110 mcg (312 subjects), fexofenadine 180 mg (311), or placebo (313) once-daily. The NRQLQ, a 16-item, selfadministered, disease-specific, quality of life instrument that measures functional problems that are most troublesome to subjects with nocturnal allergy symptoms, was administered at randomization and at end of study. NRQLQ items are scored from 0 to 6, with higher scores indicating greater nocturnal impairment. Items are grouped into four domains: sleep problems; sleep time problems; symptoms on waking in the morning; and practical problems. An overall score is calculated from the mean score of all items. Mean change from baseline (MCFB) treatment differences in overall NRQLQ were analyzed using an analysis of covariance model. RESULTS: Baseline NRQLQ global and individual domains scores were similar across treatment groups. MCFB differences in overall NRQLQ scores were significantly (p < 0.001) different with FFNS compared with placebo (-0.6, 95% CI -0.8, 0.1) and FEX (-0.5, 95% CI -0.7, -0.3) MCFB differences between FEX and placebo were not significantly different (-0.1, 95% CI -0.4, 0.1). CONCLUSIONS: Subjects treated with FFNS had significant improvements in their rhinitis-related nocturnal quality of life compared with both FEX and placebo, while those treated with FEX did not show significant improvement over placebo. Funding: GlaxoSmithKline
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Abstracts S53
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
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Low Systemic Bioavailability of Ciclesonide Aqueous Nasal Spray and Ciclesonide HFA Nasal Aerosol Compared With Orally Inhaled Ciclesonide M. Weiswasser1, J. Zhu2, V. Chia1, R. Nave3, M. Wingertzahn1; 1 ALTANA Pharma US, A NYCOMED Company, Florham Park, NJ, 2 ALTANA Pharma US, A Nycomed Company, Florham Park, NJ, 3Altana Pharma AG, Konstanz, GERMANY. RATIONALE: This study investigated the pharmacokinetics of 2 ciclesonide formulations for allergic rhinitis, an aqueous nasal spray and a hydro-fluoro-alkane (HFA) nasal aerosol, compared with a solution formulation of ciclesonide for treatment of asthma focusing on desisobutyryl-ciclesonide (des-CIC), the pharmacologically active metabolite of ciclesonide. METHODS: Healthy volunteers ( 18 years; N 5 30) were randomized in an open-label, single-dose, 3-period crossover study to 300 mg ciclesonide aqueous nasal spray, 300 mg ciclesonide HFA nasal aerosol (ciclesonide-HFA), or 320 mg ciclesonide orally inhaled by a metered-dose inhaler (MDI). Primary pharmacokinetic parameters are area under the serum concentration time curve extrapolated to infinity (AUCinf) and maximum serum concentraton (Cmax) of des-CIC. The safety and tolerability of ciclesonide were also evaluated. RESULTS: Concentrations of des-CIC above 10 pg/mL (5 lower limit of quantification) were detected in only 3% of the serum samples in volunteers receiving ciclesonide aqueous. The highest value of des-CIC for this treatment was 26.7 pg/mL. Hence, bioavailability is too low to characterize pharmacokinetic properties accurately for this formulation. Mean Cmax (ng/L) of des-CIC for ciclesonide-HFA and orally inhaled ciclesonide were 59.1 and 586.2, respectively. Mean AUCinf of des-CIC for ciclesonide-HFA and for orally inhaled ciclesonide were 397.5 and 2,685 ngdh/L, respectively. The exposure of des-CIC following intranasal administration of HFA nasal is 14.3% compared to the inhalation using the same formulation via MDI. CONCLUSIONS: The systemic bioavailability of des-CIC was low for both nasal ciclesonide formulations compared with orally inhaled ciclesonide with that of aqueous nasal spray lower than that of HFA nasal aerosol.
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Effectiveness of Ciclesonide Nasal Aerosol in Adult and Adolescent Patients With Seasonal Allergic Rhinitis (SAR) J. van Bavel1, C. LaForce2, E. Meltzer3, V. Chia4, P. Darken4, M. Wingertzahn4; 1Allergy and Asthma Association, Austin, TX, 2University of North Carolina School of Medicine, Raleigh, NC, 3Allergy and Asthma Medical Group and Research Center, San Diego, CA, 4ALTANA Pharma US Inc, A Nycomed Company, Florham Park, NJ. RATIONALE: Corticosteroid aqueous nasal sprays are effective treatments for allergic rhinitis; however, aerosol-based nasal formulations are preferred by some patients. This dose-ranging study evaluated the effectiveness of a hydro-fluoro-alkane (HFA) nasal aerosol formulation of ciclesonide. METHODS: Adult and adolescent patients ( 12 years) with a history of SAR were randomized in a double-blind manner to receive ciclesonide HFA nasal aerosol 75 mg, 150 mg, or 300 mg or placebo once daily for up to 2 weeks. Efficacy was assessed by patient-reported average AM and PM reflective and instantaneous total nasal symptom scores (TNSS) and patient-reported AM instantaneous TNSS. The safety and tolerability of ciclesonide were also assessed. RESULTS: All ciclesonide HFA doses demonstrated a statistically significantly greater reduction from baseline in 24-hour reflective TNSS versus placebo (0.64 [p 5 0.011] for the75-mg group; 0.89 [p < 0.001] for 150-mg group; and 0.80 [p 5 0.001] for the 300-mg group versus placebo
on days 1 to 14]. Twenty-four hour average AM and PM instantaneous TNSS and patient-reported AM instantaneous TNSS were similar (p 0.003 for all groups versus placebo). The incidence of treatment-related adverse events was low (< 1.6% for all) and was similar among all treatment groups. CONCLUSIONS: The HFA nasal aerosol formulation of ciclesonide demonstrated statistically significant reduction in 24-hour TNSS versus placebo. Ciclesonide HFA is appropriate for further clinical phase 3 investigation.
207
Once-daily Fluticasone Furoate Nasal Spray Showed Greater Improvement In Nocturnal Quality Of Life In Subjects With Seasonal Allergic Rhinitis Compared With Oral Fexofenadine C. P. Andrews1, B. G. Martin2, R. L. Jacobs3, J. Diaz4, W. T. Toler5, B. A. Prillaman5, A. A. Dalal5, E. E. Philpot5; 1Diagnostics Research Group, San Antonio, TX, 2Southwest Allergy and Asthma Research, San Antonio, TX, 3Biogenics Research Institute, San Antonio, TX, 4 Allergy, Asthma and Immunology Associates of South Texas, San Antonio, TX, 5GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: Fluticasone Furoate Nasal Spray (FFNS), a new enhancedaffinity intranasal corticosteroid, was evaluated against oral fexofenadine (FEX) using the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ) to further characterize its therapeutic profile. METHODS: This was a randomized, double-blind, double-dummy, placebo-controlled, 2-week study (FFU109045) of 936 subjects with SAR who received either FFNS 110 mcg (312 subjects), fexofenadine 180 mg (311), or placebo (313) once-daily. The NRQLQ, a 16-item, selfadministered, disease-specific, quality of life instrument that measures functional problems that are most troublesome to subjects with nocturnal allergy symptoms, was administered at randomization and at end of study. NRQLQ items are scored from 0 to 6, with higher scores indicating greater nocturnal impairment. Items are grouped into four domains: sleep problems; sleep time problems; symptoms on waking in the morning; and practical problems. An overall score is calculated from the mean score of all items. Mean change from baseline (MCFB) treatment differences in overall NRQLQ were analyzed using an analysis of covariance model. RESULTS: Baseline NRQLQ global and individual domains scores were similar across treatment groups. MCFB differences in overall NRQLQ scores were significantly (p < 0.001) different with FFNS compared with placebo (-0.6, 95% CI -0.8, 0.1) and FEX (-0.5, 95% CI -0.7, -0.3) MCFB differences between FEX and placebo were not significantly different (-0.1, 95% CI -0.4, 0.1). CONCLUSIONS: Subjects treated with FFNS had significant improvements in their rhinitis-related nocturnal quality of life compared with both FEX and placebo, while those treated with FEX did not show significant improvement over placebo. Funding: GlaxoSmithKline
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Abstracts S53
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2