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1B STUDY OF AN INHALED FORMULATION OF ITRACONAZOLE IN HEALTHY VOLUNTEERS AND ASTHMATICS
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Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 121 (2018) S22−S62
outcomes (p value < 0.0001) indicating frozen and thawed devices fired a similar mass of epinephrine solution compared with unfrozen devices. Testing continued to show equivalence after controlling for device epinephrine dose (0.3 mg vs 0.15 mg) and expiration date, using two one-sided tests in a general linear model. Conclusions: Freezing for 24 hours did not impair EAI device’s function once thawed. While freezing is not recommended, devices accidentally left in freezing temperatures for short periods are at low risk for malfunction.
P401 ATTITUDES AND BELIEFS TOWARD EPINEPHRINE AUTO-INJECTOR PRICE INCREASE E. Wang*, A. Plunk, M. Morales, Norfolk, VA Introduction: A few years ago, the price of an epinephrine autoinjection device increased dramatically. Now with multiple options of epinephrine auto-injectors, we set out to identify what drives patient purchasing trends. Methods: Cross sectional study using an anonymous survey. The target population included parents of both male and female children who have purchased an epinephrine auto-injector within the last 10 years. The patient panel included multiple satellite CHKD allergy and immunology clinics. Results: We found that while 73% of families we surveyed “completely agreed” to feeling financially burdened by the cost of an epinephrine auto-injector (and 97% overall agreed), 68% “completely agreed” (and 93% overall agreed) to the belief in having a new auto-injector every year. 86% of families “completely agreed” in the importance of having an epinephrine auto-injector at school or daycare and only 15% of families generally worried about the side effects or harm of giving the epinephrine auto-injector. 95% of families generally felt comfortable giving the auto-injector if necessary. The number one factor in deciding which epinephrine auto-injector to purchase was physician recommendation and prescription, followed by price/insurance coverage, then pharmacy suggestion, and finally, ease of use and brand name. Conclusions: While a significant majority of our patients feel financially burdened by the cost of epinephrine auto-injectors, they also agree with the importance of purchasing it yearly. Physician recommendation and prescription is the number one deciding factor in their purchasing choice, almost three times more than cost. This study demonstrates the importance of physician awareness of the prices of medications.
P402 A PHASE 1/1B STUDY OF AN INHALED FORMULATION OF ITRACONAZOLE IN HEALTHY VOLUNTEERS AND ASTHMATICS D. Hava*,1, L. Tan2, P. Johnson3, A. Curran1, J. Perry1, S. Kramer1, K. Kane1, P. Bedwell4, D. Henderson5, G. Layton4, K. Singh6, L. Connor6, D. Singh6, J. Roach1, 1. Lexington, MA; 2. Cambridge, United Kingdom; 3. Eichenweg 3, Switzerland; 4. Kent, United Kingdom; 5. Nottingham, United Kingdom; 6. Manchester, United Kingdom Introduction: Oral itraconazole has variable pharmacokinetics and risks of significant adverse events (AEs) associated with high plasma exposure. A dry powder inhalation formulation of itraconazole (ITRA) is being developed to treat Allergic Bronchopulmonary Aspergillosis (ABPA). This study was conducted to evaluate safety, tolerability and pharmacokinetics of ITRA in healthy volunteers and asthmatics. Methods: The study was a 3-part, multi-center, open-label study. Healthy volunteers (n=5-6/cohort) received either single (Part 1 5mg, 10mg, 25mg, 35mg) or multiple doses of ITRA (Part 2 -10mg, 20mg, 35mg) over 14d. In Part 3 stable, adult asthmatics received a single dose of 20mg ITRA or 200mg of oral itraconazole in a 2-period cross-over design. Itraconazole plasma (Parts 1-3) and sputum (Part 3) concentrations were evaluated.
Results: All study drug-related AEs were mild, and no moderate, severe or serious study drug-related AEs were reported. The most common drug-related AE was the infrequent occurrence of mild cough. At steady-state, ITRA resulted in plasma exposure (AUC0-24h) that was 100-400 fold lower across doses tested than reported for oral itraconazole. In asthmatics, ITRA achieved Cmax sputum concentrations 45-fold higher and plasma AUC0-24h concentrations 85-fold lower than oral itraconazole. Conclusions: ITRA was safe and well-tolerated under the study conditions tested, and achieved significantly higher lung and lower plasma exposure compared to oral itraconazole, supporting the potential of ITRA to improve upon both the efficacy and safety profile observed with oral itraconazole in patients with ABPA.
P403 MULTIPHASIC TREATMENT MODALITY FOR PEDIATRIC EOSINOPHILIC GASTROENTERITIS, A SINGLE CENTER EXPERIENCE K. Kennedy*, M. Ruffner, A. Muir, Philadelphia, PA Introduction: Treatment of eosinophilic gastroenteritis (EG) in pediatrics is challenging. Options available include systemic immune modulators as well as targeted dietary restriction. Both regimens are difficult to adhere to given the adverse effects of systemic steroid therapy and compliance difficulties with diet restriction. At our institution we have found that only 25% of patients with EG respond to diet restriction. Here we describe the presentation and outcome of pediatric EG patients placed on a unique multiphasic steroid treatment. This treatment modality has not been previously described and is novel in its delivery pharmacokinetics which enable targeted local steroid delivery to areas beyond the esophagus. Methods: Seven patients with biopsy proven EG treated with a regimen of multiphasic steroids were reviewed. Endoscopy results including visualization and gastric eosinophil count were compared before and several months after treatment. When available, the effect of treatment on serum absolute eosinophil count, albumin and total protein was compared. Results: All patients had improvement on biopsy after initiation of multiphasic therapy with most showing resolution of gastric eosinophils. The most common modality used was at least one capsule crushed and one capsule opened of budesonide 3mg. Most patients were not on concurrent diet restriction unless they had known IgE mediated sensitization or self-restricted. The age range at initiation was 1-17 years with more patients starting treatment in adolescence. Five of the seven patients reviewed had atopic disease. Conclusions: We present our experience and promising outcomes in using a novel, targeted steroid treatment for pediatric patients with EG.
P404 FACTORS ASSOCIATED WITH THE INITIATION OF BIOLOGIC DRUGS IN MEDICAID PATIENTS WITH SEVERE UNCONTROLLED ASTHMA D. Bukstein*, fitchburg, WI Introduction: Severe Uncontrolled asthma is associated with high health care costs, yet guidance is lacking on how early to initiate biologic drugs. Few studies have examined the factors associated with the transition from nonbiologic drugs to biologics. Objective: To examine patient sociodemographics, medication use patterns, and clinical characteristics associated with lack of initiation of biologic drugs in the treatment of severe uncontrolled asthma. Methods: This was a prospective study using the Wisconsin Medicaid patients that were seen in an entirely Medicaid clinic in an underserved area of Milwaukee, Wisconsin. 31 consecutive Medicaid patients with severe uncontrolled asthma were interviewed.
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 121 (2018) S22−S62
outcomes (p value < 0.0001) indicating frozen and thawed devices fired a similar mass of epinephrine solution compared with unfrozen devices. Testing continued to show equivalence after controlling for device epinephrine dose (0.3 mg vs 0.15 mg) and expiration date, using two one-sided tests in a general linear model. Conclusions: Freezing for 24 hours did not impair EAI device’s function once thawed. While freezing is not recommended, devices accidentally left in freezing temperatures for short periods are at low risk for malfunction.
P401 ATTITUDES AND BELIEFS TOWARD EPINEPHRINE AUTO-INJECTOR PRICE INCREASE E. Wang*, A. Plunk, M. Morales, Norfolk, VA Introduction: A few years ago, the price of an epinephrine autoinjection device increased dramatically. Now with multiple options of epinephrine auto-injectors, we set out to identify what drives patient purchasing trends. Methods: Cross sectional study using an anonymous survey. The target population included parents of both male and female children who have purchased an epinephrine auto-injector within the last 10 years. The patient panel included multiple satellite CHKD allergy and immunology clinics. Results: We found that while 73% of families we surveyed “completely agreed” to feeling financially burdened by the cost of an epinephrine auto-injector (and 97% overall agreed), 68% “completely agreed” (and 93% overall agreed) to the belief in having a new auto-injector every year. 86% of families “completely agreed” in the importance of having an epinephrine auto-injector at school or daycare and only 15% of families generally worried about the side effects or harm of giving the epinephrine auto-injector. 95% of families generally felt comfortable giving the auto-injector if necessary. The number one factor in deciding which epinephrine auto-injector to purchase was physician recommendation and prescription, followed by price/insurance coverage, then pharmacy suggestion, and finally, ease of use and brand name. Conclusions: While a significant majority of our patients feel financially burdened by the cost of epinephrine auto-injectors, they also agree with the importance of purchasing it yearly. Physician recommendation and prescription is the number one deciding factor in their purchasing choice, almost three times more than cost. This study demonstrates the importance of physician awareness of the prices of medications.
P402 A PHASE 1/1B STUDY OF AN INHALED FORMULATION OF ITRACONAZOLE IN HEALTHY VOLUNTEERS AND ASTHMATICS D. Hava*,1, L. Tan2, P. Johnson3, A. Curran1, J. Perry1, S. Kramer1, K. Kane1, P. Bedwell4, D. Henderson5, G. Layton4, K. Singh6, L. Connor6, D. Singh6, J. Roach1, 1. Lexington, MA; 2. Cambridge, United Kingdom; 3. Eichenweg 3, Switzerland; 4. Kent, United Kingdom; 5. Nottingham, United Kingdom; 6. Manchester, United Kingdom Introduction: Oral itraconazole has variable pharmacokinetics and risks of significant adverse events (AEs) associated with high plasma exposure. A dry powder inhalation formulation of itraconazole (ITRA) is being developed to treat Allergic Bronchopulmonary Aspergillosis (ABPA). This study was conducted to evaluate safety, tolerability and pharmacokinetics of ITRA in healthy volunteers and asthmatics. Methods: The study was a 3-part, multi-center, open-label study. Healthy volunteers (n=5-6/cohort) received either single (Part 1 5mg, 10mg, 25mg, 35mg) or multiple doses of ITRA (Part 2 -10mg, 20mg, 35mg) over 14d. In Part 3 stable, adult asthmatics received a single dose of 20mg ITRA or 200mg of oral itraconazole in a 2-period cross-over design. Itraconazole plasma (Parts 1-3) and sputum (Part 3) concentrations were evaluated.
Results: All study drug-related AEs were mild, and no moderate, severe or serious study drug-related AEs were reported. The most common drug-related AE was the infrequent occurrence of mild cough. At steady-state, ITRA resulted in plasma exposure (AUC0-24h) that was 100-400 fold lower across doses tested than reported for oral itraconazole. In asthmatics, ITRA achieved Cmax sputum concentrations 45-fold higher and plasma AUC0-24h concentrations 85-fold lower than oral itraconazole. Conclusions: ITRA was safe and well-tolerated under the study conditions tested, and achieved significantly higher lung and lower plasma exposure compared to oral itraconazole, supporting the potential of ITRA to improve upon both the efficacy and safety profile observed with oral itraconazole in patients with ABPA.
P403 MULTIPHASIC TREATMENT MODALITY FOR PEDIATRIC EOSINOPHILIC GASTROENTERITIS, A SINGLE CENTER EXPERIENCE K. Kennedy*, M. Ruffner, A. Muir, Philadelphia, PA Introduction: Treatment of eosinophilic gastroenteritis (EG) in pediatrics is challenging. Options available include systemic immune modulators as well as targeted dietary restriction. Both regimens are difficult to adhere to given the adverse effects of systemic steroid therapy and compliance difficulties with diet restriction. At our institution we have found that only 25% of patients with EG respond to diet restriction. Here we describe the presentation and outcome of pediatric EG patients placed on a unique multiphasic steroid treatment. This treatment modality has not been previously described and is novel in its delivery pharmacokinetics which enable targeted local steroid delivery to areas beyond the esophagus. Methods: Seven patients with biopsy proven EG treated with a regimen of multiphasic steroids were reviewed. Endoscopy results including visualization and gastric eosinophil count were compared before and several months after treatment. When available, the effect of treatment on serum absolute eosinophil count, albumin and total protein was compared. Results: All patients had improvement on biopsy after initiation of multiphasic therapy with most showing resolution of gastric eosinophils. The most common modality used was at least one capsule crushed and one capsule opened of budesonide 3mg. Most patients were not on concurrent diet restriction unless they had known IgE mediated sensitization or self-restricted. The age range at initiation was 1-17 years with more patients starting treatment in adolescence. Five of the seven patients reviewed had atopic disease. Conclusions: We present our experience and promising outcomes in using a novel, targeted steroid treatment for pediatric patients with EG.
P404 FACTORS ASSOCIATED WITH THE INITIATION OF BIOLOGIC DRUGS IN MEDICAID PATIENTS WITH SEVERE UNCONTROLLED ASTHMA D. Bukstein*, fitchburg, WI Introduction: Severe Uncontrolled asthma is associated with high health care costs, yet guidance is lacking on how early to initiate biologic drugs. Few studies have examined the factors associated with the transition from nonbiologic drugs to biologics. Objective: To examine patient sociodemographics, medication use patterns, and clinical characteristics associated with lack of initiation of biologic drugs in the treatment of severe uncontrolled asthma. Methods: This was a prospective study using the Wisconsin Medicaid patients that were seen in an entirely Medicaid clinic in an underserved area of Milwaukee, Wisconsin. 31 consecutive Medicaid patients with severe uncontrolled asthma were interviewed.