Azelastine hydrochloride displayed no sensitising potential in the guinea pig. Azelastine demonstrated no genotoxic potential in a battery of in vitro and in vivo tests, nor any carcinogenic potential in rats or mice. In male and female rats, azelastine at oral doses greater than 3 mg/kg/day caused a dose-related decrease in the fertility index; no substance-related alterations were found in the reproductive organs of males or females during chronic toxicity studies, however, embryotoxic and teratogenic effects in rats, mice and rabbits occurred only at maternal toxic doses (for example, skeletal malformations were observed in rats and mice at doses of mg/kg/day).
Results shown are from a 12-week, multicenter, randomized, double-blind, parallel-group study of 349 patients aged 12 years and older, with asthma (mean baseline forced expiratory volume in 1 second [FEV 1 ] 66% to 69% predicted) previously treated with medium doses of inhaled corticosteroids. Patients were randomized to treatment with ADVAIR DISKUS 250/50, fluticasone propionate 250 mcg, salmeterol 50 mcg, or placebo, each given twice daily through the DISKUS device. Patients were withdrawn from the study because of worsening asthma if they met any of the following criteria: a clinical exacerbation requiring emergency treatment, hospitalization, or use of asthma medication not allowed by the study protocol; a decrease in FEV 1 of more than 20% from the predose FEV 1 at the randomization visit; more than a 20% decrease from the mean morning baseline PEF (peak expiratory flow) on more than 3 of 7 days immediately preceding a visit; 12 or more albuterol puffs per day on more than 2 of 7 days immediately preceding a visit; or more than 2 nights with awakenings caused by asthma symptoms that required albuterol during the 7 days immediately preceding a clinic visit.