Abstract
Azelastine hydrochloride is a potent second-generation antihistamine, available in Europe and the USA as a nasal spray formulation for the treatment of allergic rhinitis symptoms. GlaxoSmithKline (GSK) Consumer Healthcare has developed a new nasal formulation of azelastine hydrochloride. The present study was aimed at comparing the clinical pharmacokinetic profiles and assessing the bioequivalence of the new formulation of azelastine hydrochloride with a marketed reference nasal spray product. This was a randomized, two-way crossover, two-stage, single-dose pharmacokinetic study with 2 weeks washout between the two treatment periods. A dosage of 0.28 mg of the test and reference products was administered as a single dose to healthy volunteers according to the crossover design. Twenty-three subjects (15 subjects from stage 1 and 8 subjects from stage 2) were enrolled in the study. Adjusted mean values for AUC0–t were 1,526.8 h pg/mL for the test drug and 1,441.5 h pg/mL for the reference drug; for C max the values were 61.59 pg/mL for the test drug and 58.21 pg/mL for the reference drug. The 94.12 % CI of geometric mean ratios (test/reference) were 0.99–1.13 and 0.95–1.18 for AUC0–t and C max. This met the predefined criteria for bioequivalence between test and reference drugs. Secondary pharmacokinetic parameters for azelastine and for the metabolite desmethyl azelastine, AUC(0–∞) and t max, were numerically similar between the two study treatments. Both test and reference azelastine hydrochloride formulations were well tolerated at single dose. This study demonstrated the bioequivalence between the new azelastine hydrochloride nasal spray formulation and the marketed reference Allergodil® after single-dose administration.
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Acknowledgments
The authors appreciate the excellent help in preparing the manuscript and support of the study by Renata Perego, Elena Tedeschi and Sharron Ashburner. We also thank Dr. Nick P. Kronfield and Mairead North for their critical discussion of the study design and manuscript review. This study was sponsored by GlaxoSmithKline Consumer Healthcare.
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Du, D., Targett, D., Stolberg, E. et al. A clinical pharmacokinetic study comparing two azelastine hydrochloride nasal formulations in a single-dose design. Eur J Drug Metab Pharmacokinet 39, 69–75 (2014). https://doi.org/10.1007/s13318-013-0134-0
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DOI: https://doi.org/10.1007/s13318-013-0134-0