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Efficacy and Safety of Ciclesonide Nasal Spray for the Treatment of Seasonal Allergic Rhinitis
S168 Abstracts
Efficacy and Safety of Ciclesonide Nasal Spray for the Treatment of Seasonal Allergic Rhinitis P. H. Ratner1, J. H. van Bavel2, P. Darken3, N. Hall4, T. Shah5, M. A. Wingertzahn6; 1Sylvana Research, San Antonio, TX, 2Allergy & Asthma Associates, Austin, TX, 3Director, Biostatistics and Data Management, Altana Pharma, Florham Park, NJ, 4Associate Director, Biostatistics, Altana Pharma, Florham Park, NJ, 5Scientific and Clinical Development, Altana Pharma, Florham Park, NJ, 6Clinical Project Head, Altana Pharma, Florham Park, NJ. RATIONALE: Intranasal corticosteroids are considered the most effective treatment for the management of allergic rhinitis (AR) symptoms. The objective of this study was to evaluate the efficacy and safety of a new corticosteroid in development for the treatment of asthma and AR, ciclesonide (CIC), in patients with seasonal AR (SAR). METHODS: In this phase III, double-blind, placebo-controlled trial, patients with SAR (age 12 years) were randomized to receive intranasal CIC 200 g (n = 164) or placebo (n = 163) once daily for 28 days. Patientassessed total nasal symptom score (TNSS), physician-assessed overall nasal signs and symptoms severity (PANS), and Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) were evaluated. Adverse events (AEs) were monitored throughout the study. RESULTS: Ciclesonide significantly improved the average of am and pm reflective TNSS and instantaneous TNSS versus placebo from Days 1 through 14 (primary endpoint) and over the 28-day treatment period (p < 0.001). Furthermore, CIC showed similar improvements in both am and pm placebo-adjusted reflective TNSS, suggesting a 24-hour effect. At Day 15, CIC improved RQLQ by -1.17 ± 0.10 compared with improvement of -0.72 ± 0.10 with placebo (p = 0.002). The frequency of treatment-related AEs was low and comparable between treatment groups, and the placeboadjusted epistaxis rate for CIC was 1.8%. CONCLUSIONS: Ciclesonide administered intranasally was superior to placebo in relieving nasal symptoms in adult and adolescent patients with SAR. Ciclesonide was well tolerated, with a safety profile comparable with placebo and a low epistaxis rate. These data support the continued clinical development of CIC nasal spray. Funding: Altana Pharma
653
SUNDAY
A Double-Blind Comparison of Efficacy of 0.1% Tacrolimus Ophthalmic Ointment and 2% Cyclosporine Eye Drop Vernal Keratoconjunctivitis (vkc) P. Labcharoenwongs1, W. Durongpisitkul2, P. Dumrongkigchaiporn3, O. Jirapongsananuruk1, N. Visitsunthorn1, P. Kosrirukvongs4, W. Booranapong4, P. Vichyanond1; 1Pediatric, Siriraj hospital, Bangkok, THAILAND, 2Pediatric, Police general hospital, Bangkok, THAILAND, 3Pediatric, Bangkok Pattaya hospital, Chonburi, THAILAND, 4Opthalmology, Siriraj hospital, Bangkok, THAILAND. RATIONALE: To compare the efficacy of 0.1% tacrolimus (FK-506) ophthalmic ointment and 2% cyclosporine eye drop VKC. METHODS: After 2 weeks washout period, 24 cases of VKC were randomized into 2 groups in a double-blinded, parallel fashion. The first group received 0.1% FK-506 eye ointment plus placebo eye drop and the 2nd group received cyclosporine eye drops plus placebo ointment for 8 weeks, follow by open treatment with 0.1% FK-506 eye ointment for 4 weeks in both groups. Subjective ocular symptoms and side effects were scored by patients at the entry, 1st, 4th, 8th and 12th weeks. Objective ocular signs were evaluated by one ophthalmologist. RESULTS: Twenty-four cases (23 boys) of VKC were enrolled with mean ages of 9.61+2.55 years. Mean duration of VKC was 3.07+2.28 years. There was no difference between the two groups in subjective, objective and side effect scores at the entry, 1st, 4th, 8th, and 12th weeks. Compared to baseline, the subjective scores at the 4th and 8th weeks decreased significantly in both groups. In contrast, the objective scores at the 4th and 8th week decreased significantly in FK-506 group only (p = 0.003, p = 0.001, respectively). The side effect scores at the 8th week reduced significantly in the FK-506 group only. (p = 0.004). CONCLUSIONS: The efficacy of 0.1% FK-506 eye ointment and cyclosporine are comparable for the treatment of VKC. However, total
654
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
objective scores (after 4th week) and side effect scores (after 8th week) improves only with FK-506. Effect of Anti-Allergic Herbal Extract, SA-2121, on the Development of Allergic Conjunctivitis J. Davidson1, S. Baik1, Z. Yao2, R. Martin2, C. K. Oh1; 1Harbor-UCLA Medical Center, Torrance, CA, 2Tanox Inc., Houston, TX. RATIONALE: Severe allergic conjunctivitis such as atopic and vernal keratoconjunctivitis is a sight-threatening clinical entity. We previously demonstrated that SA-2121 has anti-allergic properties in a murine model of atopic asthma. We now determined whether SA-2121 prevents the development of allergic conjunctivitis. METHODS: SWR/J mice were given an intraperitoneal injection of ovalbumin (OVA), aluminum hydroxide (ALUM), and pertussis toxin. Five days later, they received a booster injection of OVA alone subcutaneously at the back. Eighteen days after the first immunization, the mice were used as actively sensitized animals. Mice were actively immunized with OVA, and conjunctivitis was induced by topical instillation of OVA. Five or 10 microliters of SA-2121 (500 micrograms/microliter) was administered to each eye 30 minutes before OVA challenge. Conjunctival tissue was obtained 30 minutes after OVA challenge. Objective clinical scores including tearing, chemosis, erythema, edema and rubbing were assigned and conjunctival TNF-alpha levels were measured by real-time reverse transcriptase polymerase chain reaction. RESULTS: OVA-challenged mice showed markedly increased chemosis, erythema, edema, rubbing as compared to phosphate-buffered saline (PBS) challenged control mice. Conjunctival tissue from OVA-challenged mice showed 6-fold increase in TNF-alpha mRNA level compared to PBS-challenged control mice. Pre-treatment with SA-2121 markedly attenuated development of clinical symptoms of allergic conjunctivitis in a dose-dependent fashion and TNF-alpha by up to 90% compared to OVA-challenged tissue without SA-2121 treatment. CONCLUSIONS: Anti-allergic herbal extract, SA-2121, may prevent the development of allergic conjunctivitis by suppressing the expression of pro-inflammatory cytokines such as TNF-alpha. Funding: AAAAI
655
656
House Dust Mite Allergy causing Otitis Externa
R. S. Kaulsay1, P. P1, Y. Yeow1, L. Rampal2, I. Hidayah3; 1Dept of ENT Surgery, University Putra Malaysia, Kuala Lumpur, MALAYSIA, 2Dept of Community Health Medicine, University Putra Malaysia, Kuala Lumpur, MALAYSIA, 3Dept of Biomedical Science, University Technology Malaysia, Kuala Lumpur, MALAYSIA. RATIONALE: Do House Dust Mites Cause Otitis Externa. METHODS: This Prospective Case Control Study was undertaken to investigate the correlation between Otitis Externa and the Sensitization and presence of House Dust Mite in the External Auditory Canal. This multicentre study was conducted from October 2004 to April 2005 in two centres here. Fifty patients were enrolled of whom 29 had Otitis Externa and 21 were controls with no ear symptoms.All 29 positives presented with one more of following symptoms; itching, hearing loss, otalgia, swollen and narrowing of the canal lumen or otorrhea. A detailed questionnaire was completed, sample of cerumen (earwax) were taken from subjects, microscopic observation of the cerumen (earwax), and skin prick tests was performed. Informed consent was taken prior to carrying out the procedures. RESULTS: Out of the 29 Otitis Externa patients, 18 (82%) of them were sensitized to House Dust Mite and only 1 (3.4 %) had physical presence of the House Dust Mite in the earwax sample. Meanwhile in control subjects, 4 (19%) were sensitized to House Dust Mite, and none of them had physical presence of the House Dust Mite in the earwax sample. CONCLUSIONS: From the study we conclude that, significantly more people with Otitis Externa were sensitized to House Dust Mite compared to the controls group as seen by the skin prick test results.
Efficacy and Safety of Ciclesonide Nasal Spray for the Treatment of Seasonal Allergic Rhinitis P. H. Ratner1, J. H. van Bavel2, P. Darken3, N. Hall4, T. Shah5, M. A. Wingertzahn6; 1Sylvana Research, San Antonio, TX, 2Allergy & Asthma Associates, Austin, TX, 3Director, Biostatistics and Data Management, Altana Pharma, Florham Park, NJ, 4Associate Director, Biostatistics, Altana Pharma, Florham Park, NJ, 5Scientific and Clinical Development, Altana Pharma, Florham Park, NJ, 6Clinical Project Head, Altana Pharma, Florham Park, NJ. RATIONALE: Intranasal corticosteroids are considered the most effective treatment for the management of allergic rhinitis (AR) symptoms. The objective of this study was to evaluate the efficacy and safety of a new corticosteroid in development for the treatment of asthma and AR, ciclesonide (CIC), in patients with seasonal AR (SAR). METHODS: In this phase III, double-blind, placebo-controlled trial, patients with SAR (age 12 years) were randomized to receive intranasal CIC 200 g (n = 164) or placebo (n = 163) once daily for 28 days. Patientassessed total nasal symptom score (TNSS), physician-assessed overall nasal signs and symptoms severity (PANS), and Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) were evaluated. Adverse events (AEs) were monitored throughout the study. RESULTS: Ciclesonide significantly improved the average of am and pm reflective TNSS and instantaneous TNSS versus placebo from Days 1 through 14 (primary endpoint) and over the 28-day treatment period (p < 0.001). Furthermore, CIC showed similar improvements in both am and pm placebo-adjusted reflective TNSS, suggesting a 24-hour effect. At Day 15, CIC improved RQLQ by -1.17 ± 0.10 compared with improvement of -0.72 ± 0.10 with placebo (p = 0.002). The frequency of treatment-related AEs was low and comparable between treatment groups, and the placeboadjusted epistaxis rate for CIC was 1.8%. CONCLUSIONS: Ciclesonide administered intranasally was superior to placebo in relieving nasal symptoms in adult and adolescent patients with SAR. Ciclesonide was well tolerated, with a safety profile comparable with placebo and a low epistaxis rate. These data support the continued clinical development of CIC nasal spray. Funding: Altana Pharma
653
SUNDAY
A Double-Blind Comparison of Efficacy of 0.1% Tacrolimus Ophthalmic Ointment and 2% Cyclosporine Eye Drop Vernal Keratoconjunctivitis (vkc) P. Labcharoenwongs1, W. Durongpisitkul2, P. Dumrongkigchaiporn3, O. Jirapongsananuruk1, N. Visitsunthorn1, P. Kosrirukvongs4, W. Booranapong4, P. Vichyanond1; 1Pediatric, Siriraj hospital, Bangkok, THAILAND, 2Pediatric, Police general hospital, Bangkok, THAILAND, 3Pediatric, Bangkok Pattaya hospital, Chonburi, THAILAND, 4Opthalmology, Siriraj hospital, Bangkok, THAILAND. RATIONALE: To compare the efficacy of 0.1% tacrolimus (FK-506) ophthalmic ointment and 2% cyclosporine eye drop VKC. METHODS: After 2 weeks washout period, 24 cases of VKC were randomized into 2 groups in a double-blinded, parallel fashion. The first group received 0.1% FK-506 eye ointment plus placebo eye drop and the 2nd group received cyclosporine eye drops plus placebo ointment for 8 weeks, follow by open treatment with 0.1% FK-506 eye ointment for 4 weeks in both groups. Subjective ocular symptoms and side effects were scored by patients at the entry, 1st, 4th, 8th and 12th weeks. Objective ocular signs were evaluated by one ophthalmologist. RESULTS: Twenty-four cases (23 boys) of VKC were enrolled with mean ages of 9.61+2.55 years. Mean duration of VKC was 3.07+2.28 years. There was no difference between the two groups in subjective, objective and side effect scores at the entry, 1st, 4th, 8th, and 12th weeks. Compared to baseline, the subjective scores at the 4th and 8th weeks decreased significantly in both groups. In contrast, the objective scores at the 4th and 8th week decreased significantly in FK-506 group only (p = 0.003, p = 0.001, respectively). The side effect scores at the 8th week reduced significantly in the FK-506 group only. (p = 0.004). CONCLUSIONS: The efficacy of 0.1% FK-506 eye ointment and cyclosporine are comparable for the treatment of VKC. However, total
654
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
objective scores (after 4th week) and side effect scores (after 8th week) improves only with FK-506. Effect of Anti-Allergic Herbal Extract, SA-2121, on the Development of Allergic Conjunctivitis J. Davidson1, S. Baik1, Z. Yao2, R. Martin2, C. K. Oh1; 1Harbor-UCLA Medical Center, Torrance, CA, 2Tanox Inc., Houston, TX. RATIONALE: Severe allergic conjunctivitis such as atopic and vernal keratoconjunctivitis is a sight-threatening clinical entity. We previously demonstrated that SA-2121 has anti-allergic properties in a murine model of atopic asthma. We now determined whether SA-2121 prevents the development of allergic conjunctivitis. METHODS: SWR/J mice were given an intraperitoneal injection of ovalbumin (OVA), aluminum hydroxide (ALUM), and pertussis toxin. Five days later, they received a booster injection of OVA alone subcutaneously at the back. Eighteen days after the first immunization, the mice were used as actively sensitized animals. Mice were actively immunized with OVA, and conjunctivitis was induced by topical instillation of OVA. Five or 10 microliters of SA-2121 (500 micrograms/microliter) was administered to each eye 30 minutes before OVA challenge. Conjunctival tissue was obtained 30 minutes after OVA challenge. Objective clinical scores including tearing, chemosis, erythema, edema and rubbing were assigned and conjunctival TNF-alpha levels were measured by real-time reverse transcriptase polymerase chain reaction. RESULTS: OVA-challenged mice showed markedly increased chemosis, erythema, edema, rubbing as compared to phosphate-buffered saline (PBS) challenged control mice. Conjunctival tissue from OVA-challenged mice showed 6-fold increase in TNF-alpha mRNA level compared to PBS-challenged control mice. Pre-treatment with SA-2121 markedly attenuated development of clinical symptoms of allergic conjunctivitis in a dose-dependent fashion and TNF-alpha by up to 90% compared to OVA-challenged tissue without SA-2121 treatment. CONCLUSIONS: Anti-allergic herbal extract, SA-2121, may prevent the development of allergic conjunctivitis by suppressing the expression of pro-inflammatory cytokines such as TNF-alpha. Funding: AAAAI
655
656
House Dust Mite Allergy causing Otitis Externa
R. S. Kaulsay1, P. P1, Y. Yeow1, L. Rampal2, I. Hidayah3; 1Dept of ENT Surgery, University Putra Malaysia, Kuala Lumpur, MALAYSIA, 2Dept of Community Health Medicine, University Putra Malaysia, Kuala Lumpur, MALAYSIA, 3Dept of Biomedical Science, University Technology Malaysia, Kuala Lumpur, MALAYSIA. RATIONALE: Do House Dust Mites Cause Otitis Externa. METHODS: This Prospective Case Control Study was undertaken to investigate the correlation between Otitis Externa and the Sensitization and presence of House Dust Mite in the External Auditory Canal. This multicentre study was conducted from October 2004 to April 2005 in two centres here. Fifty patients were enrolled of whom 29 had Otitis Externa and 21 were controls with no ear symptoms.All 29 positives presented with one more of following symptoms; itching, hearing loss, otalgia, swollen and narrowing of the canal lumen or otorrhea. A detailed questionnaire was completed, sample of cerumen (earwax) were taken from subjects, microscopic observation of the cerumen (earwax), and skin prick tests was performed. Informed consent was taken prior to carrying out the procedures. RESULTS: Out of the 29 Otitis Externa patients, 18 (82%) of them were sensitized to House Dust Mite and only 1 (3.4 %) had physical presence of the House Dust Mite in the earwax sample. Meanwhile in control subjects, 4 (19%) were sensitized to House Dust Mite, and none of them had physical presence of the House Dust Mite in the earwax sample. CONCLUSIONS: From the study we conclude that, significantly more people with Otitis Externa were sensitized to House Dust Mite compared to the controls group as seen by the skin prick test results.