Safety assesments

Safety and tolerability were evaluated by monitoring patients for event (regardless of suspected
causality) thoughthout the run in and treatment period and for 2 week after the completion of
treatment. In addition, changes in vital signs, physical examinations, and electrocardiogram findings
between the first visit were also evaluated, as were changes in laboratory safety parameters, which
were measured at the first (enrollment) visit and repeated on both the first and last day of the blinded
treatment period.

Statistical analysis

Efficacy analyses for all endpoints were performed for a modified intention to treat patient population
that include all randomized patients who had a baseline and at least one post treatment symptom
scores were calculated by averaging all daily symptom score during the placebo run in period; mean
treatment scores averaged all daily symptom score during the double blind treatment period. Changes
from baseline were analyzed by subtracting the mean score during 2 week of treatment was computed
for the for the primary and secondary efficacy endpoints, as derived from the symptom diaries and
from quality of life questionnaire responses. Mean symptom score were also calculated after 1 week
and 2 weeks of treatment ( by averaging all daily scores during each week of the double blind treatment
period) to evaluate the changes from baseline after both 1 and 2 week of therapy.

Treatment comparisons were based one the specific pairwise contracts using an analysis of covariance
model. The model factors for treatment and study centers, with the baseline value of the dependent
variable as a covariate. Treatment differences in least squares (LS) means obtained from the analysis of
covariance model. For the global evaluations, an analysis of variance model was used. In addition, an
analysis of global evaluations was performed using the Wilcoxon rank sum test to evaluated the
responses as collapsed into categories of better ( score of 0, 1, or 2), no change (3), or worse ( 4, 5, or 6).
Safety analyses were performed for all randomized patients; 95% confidence intervals (CI) were
computed for pairwise differences in the percentages of patients with specific adverse events and
predefined changes in laboratory tests and vital signs.

With 300 patients per group, the study had 80% power to detect a 0,12 difference in change from
baseline in daytime nasal symptom score between the combination montelukast/loratadine and
montelukast groups