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Once-Daily Fluticasone Furoate∗ Nasal Spray (FFNS) 110mcg Improves Quality of Life (QoL) in Subjects with Seasonal Allergic Rhinitis (SAR) during the ragweed season ∗USAN approved name
S304 Abstracts
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Knemometric Assessment of Short-Term Lower-Leg Growth in Children with Allergic Rhinitis (AR) treated with Fluticasone Furoate* (FF) Nasal Spray *USAN approved name J. Gradman1, M. Caldwell2, O. Wolthers1; 1Asthma and Allergy Clinic, Children´s Clinic Randers, Randers, DENMARK, 2GlaxoSmithKline, Greenford, UNITED KINGDOM. RATIONALE: FF is a novel enhanced-affinity corticosteroid being developed for treatment of AR. The study objective was to evaluate potential effects on lower-leg growth rate with once-daily FF 110mcg nasal spray versus vehicle placebo in prepubertal children 6 to 11 years of age with AR. METHODS: Fifty-eight subjects were randomized to a double-blind treatment sequence with either FF followed by placebo spray or vice versa. Each double-blind treatment was administered for 2 weeks, separated by a 2-week washout period with single-blind placebo spray. Primary Endpoint: Mean growth rate (mm/wk) in lower-leg length over 2 weeks, as determined by knemometry. The primary analysis was the non-inferiority comparison of FF versus placebo using ANCOVA, adjusting for baseline lower-leg growth rate, age, and gender. Treatment and period were included as fixed effects and subject as a random effect. RESULTS: FF was non-inferior to placebo based on the lower bound of the 95% CI being above the pre-specified non-inferiority margin of 20.20mm/wk in lower-leg growth rate. In the Growth Population (e.g., no protocol violations likely to affect accuracy of growth assessments; n 5 53), mean lower-leg growth rate was 0.40mm/wk during treatment with FF and 0.42mm/wk during placebo treatment, with a treatment difference of 20.016mm/wk (95% CI: [-0.13, 0.10]). Results in the ITT population were supportive of those in the Growth Population. CONCLUSIONS: FF 110mcg nasal spray once-daily does not affect short term growth in children with AR Funding: GlaxoSmithKline
1188
TUESDAY
Once-Daily Fluticasone Furoate* Nasal Spray (FFNS) 110mcg Improves Quality of Life (QoL) in Subjects with Seasonal Allergic Rhinitis (SAR) during the ragweed season *USAN approved name J. Given1, T. Toler2, A. Ellsworth2, R. Stanford2, E. Philpot2; 1Allergy Respiratory & Sleep Center, Canton, OH, 2GlaxoSmithkline, RTP, NC. RATIONALE: Cumulative symptoms and allergic rhinitis burden may lead to impairment in daily activities and sleep patterns, resulting in a significant effect on patients’ QoL. This study evaluated potential improvements in QoL that patients with SAR may experience following the use of FFNS, a novel enhanced high affinity steroid, administered in a unique side-actuated device. METHODS: The Rhinoconjunctivitis QoL Questionnaire (RQLQ), a 28item, self-administered, disease-specific QoL instrument was used to assess QoL changes in a randomized, double-blind, placebo-controlled, two-week trial of 299 SAR subjects (12 years) randomized to once-daily FFNS 110mcg spray or placebo spray conducted in the ragweed season. The RQLQ was administered at baseline and at end of study (Week 2/early withdrawal). An RQLQ score reduction of at least 0.5 from baseline has been determined to be a clinically meaningful difference (CMD). RESULTS: Least square mean change from baseline compared with placebo was statistically significant and clinically meaningful for the overall RQLQ score (-0.599, p<0.001). All domains: Sleep (-0.724, p<0.001), Activities (-0.588 p50.027), Non-Hay fever symptoms (-0.538, p5 0.003), Practical problems (-0.773, p<0.001), Nasal symptoms (-0.873, p<0.001) Emotional problems (-0.590, p50.002), except Eye symptoms (-0.254, p50.168) were also significantly different and met the CMD threshold compared with placebo. CONCLUSIONS: FFNS 110mcg once-daily provided significant and clinically meaningful improvements in SAR subjects’ overall rhinitisrelated QoL compared with placebo during a two-week SAR study. Funding: GlaxoSmithKline
J ALLERGY CLIN IMMUNOL JANUARY 2007
1189
Once-daily Fluticasone Furoate* Nasal Spray (FF) is Safe and Effective in The Long-term Treatment of Perennial Allergic Rhinitis (PAR) in Children Ages 2 to 11 Years *USAN approved name J. F. Maspero1, A. Rosenblut2, A. Finn, Jr, 3, J. Lim4, W. Wu4, M. Faris5, E. Philpot4; 1Allergy and Clinical Immunology Buenos Aires University, Buenos Aires, ARGENTINA, 2Hospital Dr. Sotero del Rio, Santiago, CHILE, 3National Allergy, Asthma, Urticaria Center of Charleston, Charleston, SC, 4GlaxoSmithKline, RTP, NC, 5GlaxoSmithKline, Greenfort, UNITED KINGDOM. RATIONALE: This study assessed the safety and efficacy of FF, a novel enhanced-affinity corticosteroid administered using a unique side-actuated device, during long-term treatment in children with PAR. METHODS: A 12-week, randomized, double-blind, placebo-controlled study of 558 pediatric PAR subjects (ages 2 to 11 years) treated with once-daily placebo, FF 55mcg or FF 110mcg. Safety assessments included adverse events, laboratory tests, and ECGs. Steroid-specific safety measures involved thorough nasal and ophthalmic examinations and HPA axis assessment. Total nasal symptom scores (reflective and instantaneous-r/i TNSS), which were the sum of nasal congestion, itching, rhinorrhea, and sneezing symptom scores on a 0-3 (none-severe) scale, were collected. Efficacy evaluation was based on data collected over the first 4 weeks of treatment from patients 6 to 11 years of age; data from patients 2 to 11 years of age were supportive. Allergy rescue medication was provided after Week 4. RESULTS: No safety issues with either active dose were identified from AE reporting, ophthalmic and nasal examinations, ECGs, laboratory tests, or HPA axis assessment. For patients 6 to 11 years of age, the 55mcg dose demonstrated significantly greater reductions in daily rTNSS and morning, pre-dose, iTNSS compared with placebo, when adjusted for baseline value, age, sex, and country; with the 110mcg dose, only the morning, pre-dose, iTNSS showed significant reduction. For patients 2 to 11 years of age, both doses demonstrated significantly greater reduction in both endpoints. CONCLUSION: Once-daily FF nasal spray is safe and effective in the long-term management of PAR in children 2 to 11 years of age. Funding: GlaxoSmithKline
1190
Once-daily Fluticasone Furoate* Nasal Spray (FF) Provides 24-hour Symptom Relief In Subjects With Seasonal Allergic Rhinitis (SAR) Caused By Mountain Cedar Pollen *USAN approved name F. C. Hampel, Jr, 1, R. Jacobs2, B. Martin3, T. Toler4, A. Ellsworth4, E. Philpot4; 1Central Texas Health Research, New Braunfels, TX, 2Biogenics Research Institute, San Antonio, TX, 3Southwest Allergy and Asthma Research, San Antonio, TX, 4GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: FF is a novel enhanced-affinity steroid being developed for the treatment of rhinitis. METHODS: Three hundred two subjects (12 years) with active SAR to mountain cedar pollen were randomized to once-daily FF 110mcg or placebo spray administered in a unique, side-actuated device. Primary endpoint: Mean change from baseline (MCFB) over the entire 2-week treatment period in daily reflective total nasal symptoms scores (rTNSS), which was the sum of 4 symptoms: nasal congestion, itching, rhinorrhea, and sneezing. Key secondary endpoints were MCFB in AM pre-dose instantaneous total nasal symptoms scores (iTNSS), overall response to therapy (ORT), and MCFB in daily reflective total ocular symptoms scores (rTOSS). Total ocular scores were the sum of 3 symptoms: eye itching/burning; tearing/watering; and redness. Nasal and ocular symptom data were analyzed using ANCOVA. ORT was analyzed using logistic regression. RESULTS: For the primary endpoint, MCFB in rTNSS, FF 110mcg was significantly more effective at improving the nasal symptoms of SAR compared with placebo (p 5 0.003). FF 110mcg also was significantly more effective for the key secondary endpoints: MCFB in AM pre-dose iTNSS (p <0.001), ORT (p <0.001), and MCFB in rTOSS (p 50.008). The incidence of epistaxis was 7% and 5% in the placebo and FF groups,
1187
Knemometric Assessment of Short-Term Lower-Leg Growth in Children with Allergic Rhinitis (AR) treated with Fluticasone Furoate* (FF) Nasal Spray *USAN approved name J. Gradman1, M. Caldwell2, O. Wolthers1; 1Asthma and Allergy Clinic, Children´s Clinic Randers, Randers, DENMARK, 2GlaxoSmithKline, Greenford, UNITED KINGDOM. RATIONALE: FF is a novel enhanced-affinity corticosteroid being developed for treatment of AR. The study objective was to evaluate potential effects on lower-leg growth rate with once-daily FF 110mcg nasal spray versus vehicle placebo in prepubertal children 6 to 11 years of age with AR. METHODS: Fifty-eight subjects were randomized to a double-blind treatment sequence with either FF followed by placebo spray or vice versa. Each double-blind treatment was administered for 2 weeks, separated by a 2-week washout period with single-blind placebo spray. Primary Endpoint: Mean growth rate (mm/wk) in lower-leg length over 2 weeks, as determined by knemometry. The primary analysis was the non-inferiority comparison of FF versus placebo using ANCOVA, adjusting for baseline lower-leg growth rate, age, and gender. Treatment and period were included as fixed effects and subject as a random effect. RESULTS: FF was non-inferior to placebo based on the lower bound of the 95% CI being above the pre-specified non-inferiority margin of 20.20mm/wk in lower-leg growth rate. In the Growth Population (e.g., no protocol violations likely to affect accuracy of growth assessments; n 5 53), mean lower-leg growth rate was 0.40mm/wk during treatment with FF and 0.42mm/wk during placebo treatment, with a treatment difference of 20.016mm/wk (95% CI: [-0.13, 0.10]). Results in the ITT population were supportive of those in the Growth Population. CONCLUSIONS: FF 110mcg nasal spray once-daily does not affect short term growth in children with AR Funding: GlaxoSmithKline
1188
TUESDAY
Once-Daily Fluticasone Furoate* Nasal Spray (FFNS) 110mcg Improves Quality of Life (QoL) in Subjects with Seasonal Allergic Rhinitis (SAR) during the ragweed season *USAN approved name J. Given1, T. Toler2, A. Ellsworth2, R. Stanford2, E. Philpot2; 1Allergy Respiratory & Sleep Center, Canton, OH, 2GlaxoSmithkline, RTP, NC. RATIONALE: Cumulative symptoms and allergic rhinitis burden may lead to impairment in daily activities and sleep patterns, resulting in a significant effect on patients’ QoL. This study evaluated potential improvements in QoL that patients with SAR may experience following the use of FFNS, a novel enhanced high affinity steroid, administered in a unique side-actuated device. METHODS: The Rhinoconjunctivitis QoL Questionnaire (RQLQ), a 28item, self-administered, disease-specific QoL instrument was used to assess QoL changes in a randomized, double-blind, placebo-controlled, two-week trial of 299 SAR subjects (12 years) randomized to once-daily FFNS 110mcg spray or placebo spray conducted in the ragweed season. The RQLQ was administered at baseline and at end of study (Week 2/early withdrawal). An RQLQ score reduction of at least 0.5 from baseline has been determined to be a clinically meaningful difference (CMD). RESULTS: Least square mean change from baseline compared with placebo was statistically significant and clinically meaningful for the overall RQLQ score (-0.599, p<0.001). All domains: Sleep (-0.724, p<0.001), Activities (-0.588 p50.027), Non-Hay fever symptoms (-0.538, p5 0.003), Practical problems (-0.773, p<0.001), Nasal symptoms (-0.873, p<0.001) Emotional problems (-0.590, p50.002), except Eye symptoms (-0.254, p50.168) were also significantly different and met the CMD threshold compared with placebo. CONCLUSIONS: FFNS 110mcg once-daily provided significant and clinically meaningful improvements in SAR subjects’ overall rhinitisrelated QoL compared with placebo during a two-week SAR study. Funding: GlaxoSmithKline
J ALLERGY CLIN IMMUNOL JANUARY 2007
1189
Once-daily Fluticasone Furoate* Nasal Spray (FF) is Safe and Effective in The Long-term Treatment of Perennial Allergic Rhinitis (PAR) in Children Ages 2 to 11 Years *USAN approved name J. F. Maspero1, A. Rosenblut2, A. Finn, Jr, 3, J. Lim4, W. Wu4, M. Faris5, E. Philpot4; 1Allergy and Clinical Immunology Buenos Aires University, Buenos Aires, ARGENTINA, 2Hospital Dr. Sotero del Rio, Santiago, CHILE, 3National Allergy, Asthma, Urticaria Center of Charleston, Charleston, SC, 4GlaxoSmithKline, RTP, NC, 5GlaxoSmithKline, Greenfort, UNITED KINGDOM. RATIONALE: This study assessed the safety and efficacy of FF, a novel enhanced-affinity corticosteroid administered using a unique side-actuated device, during long-term treatment in children with PAR. METHODS: A 12-week, randomized, double-blind, placebo-controlled study of 558 pediatric PAR subjects (ages 2 to 11 years) treated with once-daily placebo, FF 55mcg or FF 110mcg. Safety assessments included adverse events, laboratory tests, and ECGs. Steroid-specific safety measures involved thorough nasal and ophthalmic examinations and HPA axis assessment. Total nasal symptom scores (reflective and instantaneous-r/i TNSS), which were the sum of nasal congestion, itching, rhinorrhea, and sneezing symptom scores on a 0-3 (none-severe) scale, were collected. Efficacy evaluation was based on data collected over the first 4 weeks of treatment from patients 6 to 11 years of age; data from patients 2 to 11 years of age were supportive. Allergy rescue medication was provided after Week 4. RESULTS: No safety issues with either active dose were identified from AE reporting, ophthalmic and nasal examinations, ECGs, laboratory tests, or HPA axis assessment. For patients 6 to 11 years of age, the 55mcg dose demonstrated significantly greater reductions in daily rTNSS and morning, pre-dose, iTNSS compared with placebo, when adjusted for baseline value, age, sex, and country; with the 110mcg dose, only the morning, pre-dose, iTNSS showed significant reduction. For patients 2 to 11 years of age, both doses demonstrated significantly greater reduction in both endpoints. CONCLUSION: Once-daily FF nasal spray is safe and effective in the long-term management of PAR in children 2 to 11 years of age. Funding: GlaxoSmithKline
1190
Once-daily Fluticasone Furoate* Nasal Spray (FF) Provides 24-hour Symptom Relief In Subjects With Seasonal Allergic Rhinitis (SAR) Caused By Mountain Cedar Pollen *USAN approved name F. C. Hampel, Jr, 1, R. Jacobs2, B. Martin3, T. Toler4, A. Ellsworth4, E. Philpot4; 1Central Texas Health Research, New Braunfels, TX, 2Biogenics Research Institute, San Antonio, TX, 3Southwest Allergy and Asthma Research, San Antonio, TX, 4GlaxoSmithKline, Research Triangle Park, NC. RATIONALE: FF is a novel enhanced-affinity steroid being developed for the treatment of rhinitis. METHODS: Three hundred two subjects (12 years) with active SAR to mountain cedar pollen were randomized to once-daily FF 110mcg or placebo spray administered in a unique, side-actuated device. Primary endpoint: Mean change from baseline (MCFB) over the entire 2-week treatment period in daily reflective total nasal symptoms scores (rTNSS), which was the sum of 4 symptoms: nasal congestion, itching, rhinorrhea, and sneezing. Key secondary endpoints were MCFB in AM pre-dose instantaneous total nasal symptoms scores (iTNSS), overall response to therapy (ORT), and MCFB in daily reflective total ocular symptoms scores (rTOSS). Total ocular scores were the sum of 3 symptoms: eye itching/burning; tearing/watering; and redness. Nasal and ocular symptom data were analyzed using ANCOVA. ORT was analyzed using logistic regression. RESULTS: For the primary endpoint, MCFB in rTNSS, FF 110mcg was significantly more effective at improving the nasal symptoms of SAR compared with placebo (p 5 0.003). FF 110mcg also was significantly more effective for the key secondary endpoints: MCFB in AM pre-dose iTNSS (p <0.001), ORT (p <0.001), and MCFB in rTOSS (p 50.008). The incidence of epistaxis was 7% and 5% in the placebo and FF groups,