No abstract

Studies indicate that allergy sufferers remain dissatisfied with available antiallergic therapies. A new convenient formulation of solubilized steroid combined in the same nasal spray solution with antihistamine may provide added symptom relief. The objective was to evaluate effects of CDX-947 (solubilized budesonide) and CDX-313 (solubilized azelastine + budesonide) against their suspension-type comparators (budesonide [Rhinocort Aqua {RA}] or azelastine + budesonide [Astelin] {AS} + RA]) and placebo on nasal allergy symptoms of patients exposed to controlled levels of ragweed pollen in an environmental exposure chamber (EEC). Two separate EEC studies that enrolled 173 patients were analyzed. Total nasal symptom score (TNSS) and onset of action were captured. Mean change from baseline of TNSS was compared with analysis of covariance and the onset of action determined. Meta-analysis was performed to allow cross-comparisons between studies. All active treatments significantly reduced TNSS when compared with placebo and both CDX-947 and CDX-313 showed increased improvement over the suspension-type comparators. CDX-313 provided significantly faster onset of action for itchy nose and sneezing. No clinically significant adverse events were reported in this study. The novel combination product, CDX-313, provided fast, long-lasting relief for allergic rhinitis symptoms. Compared with products where corticosteroid remains suspended, the new solubilized nasal spray formulation provides added benefit including faster onset of action and superior, convenient dosing of two therapeutics in one convenient product.

The levothyroxine soft capsule formulated with the stricter new potency guideline set forward by the Food and Drug Administration met equivalence criteria in terms of rate and extent of exposure under fasting conditions to the reference tablet formulation. Clinical doses of the capsule formulation can be given using any combination of the commercialized strengths.

No abstract

Nonallergic rhinitis (NAR) subjects present clinically with similar symptoms to subjects with allergic rhinitis, but which mechanistically are not IgE- mediated. NAR is difficult to study because of multiple, as yet unknown, disease mechanisms and lack of biomarkers and diagnostic tests. The purpose of this proof of concept pilot study was to develop an environmental exposure chamber (EEC) model to simulate weather conditions in a controlled setting to objectively diagnose NAR subjects and ultimately to investigate novel NAR therapies. Thirty-seven subjects with a history of NAR confirmed by negative skin-prick test to a panel of aeroallergens were tested with cold dry air (CDA) and temperature change challenges. Objective (acoustic rhinometry [AcR] and nasal secretions) and subjective measures (total nasal symptom scores [TNSSs]: congestion, rhinorrhea, and postnasal drip [0-3]) were collected. Data was presented as mean ± SEM and statistical significance was assessed by paired t-test. The NAR EEC AcR responders to CDA had a significant decrease in mean minimal cross-sectional area (MCA; a measure of nasal patency) of 22.2 ± 2.43% (p < 0.0001) and 6.7 ± 7.22% (not statistically significant) at 30 and 60 minutes, respectively, with a concomitant increase in TNSS of 1.0 ± 0.24 U and 1.4 ± 0.30 U, respectively. AcR responders to temperature change showed a significant decrease in mean MCA to warm air of 16.0 ± 3.82% (p < 0.001) and 19.4 ± 3.88% (p < 0.0001) at 30 and 60 minutes, respectively, with an increase of TNSS of 0.4 ± 0.25 U and 0.4 ± 0.27 U, respectively. With rapid conversion to cold air, further decrease in mean MCA accompanied by an increase in TNSS was observed at 30 and 60 minutes. Increase in rhinorrhea was highest for CDA and the cold air phase of the temperature change challenge. Using the NAR EEC model, significant symptoms were induced in response to simulated weather changes in NAR patient responders. This proof of concept pilot study shows that the EEC model provides a consistent and reliable method to phenotype weather-induced NAR subjects that could be used to investigate disease mechanisms and novel therapies for NAR.