Nc. Barnes et Jc. Pujet, PRANLUKAST, A NOVEL LEUKOTRIENE RECEPTOR ANTAGONIST - RESULTS OF THE FIRST EUROPEAN, PLACEBO-CONTROLLED, MULTICENTER CLINICAL-STUDY IN ASTHMA, Thorax, 52(6), 1997, pp. 523-527
Background - Leukotriene receptor antagonists have been shown to prote
ct against bronchoconstriction induced by antigens, exercise, and cold
air. There are relatively few clinical studies reported in patients w
ith asthma. The present study is the first clinical evaluation of pran
lukast (SE 205312, ONO-1078) outside Japan in patients with asthma. Me
thods - A randomised, double blind, placebo controlled, parallel group
, multicentre four week study of the safety and tolerability of oral p
ranlukast, 225 or 337.5 mg twice daily, was performed in patients with
mild to moderate asthma. Preliminary efficacy data were obtained; the
main efficacy variables evaluated were forced expiratory volume in on
e second (FEV1) and morning domiciliary (home) peak expiratory flow ra
tes (PEFR). Clinic PEFR and daytime and night-time asthma symptom scor
es were also recorded. Results - Compared with the placebo group the i
mprovement in morning home PEFR was statistically significant at all t
ime points for patients receiving pranlukast 337.5 mg twice daily and
at weeks 1 and 2 for those treated with pranlukast in a dose of 225 mg
twice daily. Mean morning home PEFR increased by 10.8 to 18.6 l/min (
95% CI 0.2 to 29.3 l/min) in patients treated with pranlukast compared
with a slight deterioration in those given placebo. FEV1 significantl
y increased within one hour after the first dose of pranlukast compare
d with baseline and this increase was maintained for eight hours. Impr
ovements in trough FEV1 - that is, at the end of the dosing interval -
were statistically significant for the group treated with pranlukast
225 mg twice daily compared with placebo at week 4. Mean increases in
FEV1 ranged from 210 ml to 340 ml (95% CI 60 to 500 ml) at trough in t
he pranlukast group. Patients treated with pranlukast also showed impr
ovements in summary symptom and night-time asthma scores. Pranlukast w
as well tolerated, and no drug related changes in haematological and b
iochemical variables were observed. Conclusions - Pranlukast, an oral
leukotriene receptor antagonist, is well tolerated asthma. It increase
d FEV1 within one hour of dosing, improved patient summary symptom and
night-time asthma scores, and reduced the use of rescue bronchodilato
rs, thus providing further evidence of a role for leukotrienes in the
pathogenesis of asthma.