Clinical & Experimental Allergy

Comparison of a new antihistaminic and antiallergic compound KW 4679 with terfenadine and placebo on skin and nasal provocation in atopic individuals


R. J. Davies, Department of Respiratory Medicine and Allergy, St Bartholomew's Hospital, London EC1A 7BE, UK.


The effects of three oral doses of a new compound KW 4679 thought to have both antihistaminic and antiallergic properties were compared with terfenadine and placebo in a double-blind cross-over trial in 15 volunteers with seasonal allergic rhinitis. Comparison of the effect of the treatments with either 2.5, 5 or 10mg b.i.d. of KW 4679, 60 mg b.i.d. of terfenadine or placebo was made on the response to histamine and grass pollen skin-prick testing. Nasal provocation testing with grass pollen was performed on the eighth day of treatment. Nasal airway resistance (NAR) was measured using active posterior rhinomanometry and the dose of grass pollen which caused a 200% increase in NAR was determined. The number of sneezes in the first 12min was counted. Compared with placebo all doses of KW 4679 and terfenadine significantly inhibited the skin weal response to histamine and grass pollen (P < 0.001). The inhibitory effect of KW 4679 on both histamine and allergen induced skin weals was significantly greater than that of terfenadine (P= 0.001 and P= 0.049 respectively). The results of nasal challenges with grass pollen showed that all doses of KW 4679 and terfenadine were effective in reducing sneeze counts (P < 0.001), though there were no significant effects on allergen induced increase in NAR. All three doses of KW 4679 were generally well tolerated. Drowsiness was reported by some of the volunteers on KW 4679 and one volunteer reported drowsiness whilst taking placebo. Slight and reversible rises in AST and ALT concentrations were observed; these were not considered clinically significant.