Pediatrics Publishes Study Demonstrating Safety of Singulair-R- -montelukast sodium- in Younger Children with Asthma

Business Wire, Sept 5, 2001

Business Editors/Health & Pharmaceutical Writers

UPPER GYWNEDD, Pa.--(BUSINESS WIRE)--Sept. 5, 2001

Study also showed significant improvements in exploratory efficacy

endpoints in these 2-5 year old children

In an article just published in Pediatrics, the official journal of the American Academy of Pediatrics, Singulair(R) (montelukast sodium) 4 mg was shown to be well tolerated for children ages two to five years old enrolled in a clinical study. Singulair is Merck's once-a-day medicine for the prevention and chronic treatment of asthma.

The results from this multi-national safety and exploratory efficacy study of Singulair in over 600 children were first announced at the American Thoracic Society meeting in May 2000. Results demonstrated that treatment with Singulair 4 mg was well tolerated. They show that Singulair produced improvement in daytime asthma symptoms (cough, wheeze, trouble breathing and activity limitation) compared with placebo and reduced the use of oral corticosteroids for asthma rescue. Among those parents reporting overnight asthma symptoms in their children at the start of the study, treatment with Singulair also demonstrated significant improvement in overnight asthma symptoms (cough).

"Asthma is the most common chronic disease in children. This study confirms and extends the benefits of Singulair that were previously demonstrated in adults and older children with persistent asthma to these younger children with asthma," said Barbara Knorr, M.D., senior director, Pulmonary Immunology, Merck Research Laboratories and one of the authors of the study.

Details on the published study

The results published in Pediatrics are based on data collected from 689 patients who participated in the double-blind study. Patients received either Singulair (n=461) or placebo (n=228) once daily at bedtime over a three-month period. Approximately 27 percent of the patients also received inhaled/nebulized steroids and 13 percent received inhaled/nebulized cromolyn at a constant daily dose.

The study, which was designed primarily to assess the safety profile of Singulair 4 mg in two to five year olds, showed that the side effects with Singulair were generally comparable to placebo. The most frequently reported side effects were asthma (30 percent Singulair, 38 percent placebo), fever (27 percent Singulair, 27 percent placebo) and upper respiratory infection (27 percent Singulair, 28 percent placebo). Study discontinuations were similar between Singulair 4 mg and placebo (3.5 percent Singulair, 3.1 percent placebo).

As noted earlier, the study also assessed several exploratory efficacy endpoints. Parent/caregiver reports on daily diary cards demonstrated that children on Singulair 4 mg experienced statistically significant improvements in endpoints that included daytime asthma symptom scores, overnight asthma symptom scores and percent of patients using oral corticosteroid for asthma rescue. Averaged over the 12-week treatment period, the respective mean change from baseline in daytime asthma symptom scores(1) was -0.37 and -0.26 for the Singulair and placebo groups respectively (p=0.003, mean baseline symptoms scores were 0.98 Singulair and 0.95 placebo). Statistically significant improvements in the individual daytime symptoms of cough (p=0.003), wheeze (p=0.042), trouble breathing (p=0.007), and activity limitation (p<0.001) were noted in the patients treated with Singulair compared with those receiving placebo. Children treated with Singulair also had statistically significant improvement in the overnight symptom of cough compared with placebo (p=0.026). During the treatment period, the percent of patients using oral corticosteroids for asthma rescue was significantly reduced with 19 percent of patients on Singulair and 28 percent of patients on placebo using oral corticosteroids for asthma rescue (p=0.008).(2)

Important information about Singulair

The U.S. Food and Drug Administration (FDA) approved Singulair in February 1998 as a 5 mg cherry-flavored chewable tablet for children aged 6 to 14 years and as a 10 mg tablet for adolescents and adults 15 and older for the prevention and chronic treatment of asthma. Singulair 4 mg tablets for children aged 2 to 5 years was approved by the FDA in March 2000. Singulair should be taken once daily in the evening.

The safety of Singulair 4 mg chewable tablets in pediatric patients 2 to 5 years of age was demonstrated in an interim analysis of 314 pediatric patients from this 12-week double-blind, placebo-controlled study in 689 patients. Efficacy of Singulair in this age group is extrapolated from the demonstrated efficacy in adolescent and adult patients 15 years of age and older and pediatric patients 6 to 14 years of age with asthma based on a similar mean systemic exposure (AUC), and that the disease course, pathophysiology and the drugs effect are substantially similar among these populations.

The safety and effectiveness in pediatric patients below the age of 2 years have not been established. Long-term trials evaluating the effect of chronic administration of Singulair on linear growth (height) in pediatric patients have not been conducted.