Montelukast May Lessen Pediatric Exercise-Induced Bronchospasm

SAN FRANCISCO – Compared with placebo, a single dose of montelukast attenuated exercise-induced bronchoconstriction in children within 2 hours and lasted through 24 hours post dose, results from a small study found.

Although this treatment effect of montelukast has been observed in previously published studies of adults with exercise-induced bronchoconstriction, this is the first analysis of its kind in children with the condition.

"The ability to take a single tablet and have it last for 24 hours is probably more meaningful for children than for adults, because children often engage in unplanned physical activities more than adults do," Dr. George Philip said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a multicenter study, Dr. Philip, senior director of clinical research at Merck Research Laboratories, North Wales, Pa., and his associates enrolled 66 children aged 6-14 years with pre-exercise forced expiratory volume in 1 second (FEV₁) of 70% predicted or greater and a maximum fall in FEV₁ of 20% or greater at two screening exercise challenges performed on a treadmill. Study participants were randomized to receive single-dose montelukast (4 or 5 mg) or placebo before the exercise challenges were performed at 2 and 24 hours post dose.

The primary end point was maximum percent fall in FEV₁ after exercise challenge 2 hours post dose. Secondary end points included maximum percent fall in FEV₁ after the 24-hour postdose challenge and each of the following end points at 2 and 24 hours post dose: maximum percent fall in FEV₁ categorized as less than 10%, 10%-20%, and greater than 20%; area under the curve during the 60 minutes post challenge; and time to recovery to within 5% of pre-exercise baseline.

The mean age of patients was 11 years, and 56% were male. About three-quarters (74.2%) were white, 16.7% were black, and 9.1% were from other ethnic groups.

Dr. Philip reported that the mean percent fall in FEV₁ was significantly better after the 2-hour postdose exercise challenge in the montelukast treatment group, compared with the placebo group (15.3% vs. 20%, respectively). Patients in the montelukast group also fared significantly better, compared with their counterparts in the placebo group, in maximum percent fall in FEV₁ after the 24-hour postdose exercise challenge (12.92% vs. 17.25%, respectively); the categorized maximum percent fall at 2 hours (P = .034) though not at 24 hours (P = .061); and area under the curve at 2 hours (P = .022) and 24 hours (P = .013).

There were few clinical adverse events and no serious drug-related adverse events.

Dr. Philip acknowledged that the controlled laboratory setting in which the exercise challenge took place is a limitation of the study. "Natural exercise may be different from what we did in the laboratory, where all the kids had to run on a treadmill and reach a certain heart rate so we could define a clear and reproducible exercise-induced response," he explained. "Based on that response to challenge, we showed a benefit. But the kind of exercise that’s done in a laboratory may or may not match what’s done in other settings. Also, because the use of a single dose of montelukast to prevent exercise-induced bronchoconstriction in children less than age 15 years is not currently approved by the FDA, this use is considered investigational."

Merck funded the study. Dr. Philip is a full-time employee of the company.

SAN FRANCISCO – Compared with placebo, a single dose of montelukast attenuated exercise-induced bronchoconstriction in children within 2 hours and lasted through 24 hours post dose, results from a small study found.

Although this treatment effect of montelukast has been observed in previously published studies of adults with exercise-induced bronchoconstriction, this is the first analysis of its kind in children with the condition.

"The ability to take a single tablet and have it last for 24 hours is probably more meaningful for children than for adults, because children often engage in unplanned physical activities more than adults do," Dr. George Philip said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a multicenter study, Dr. Philip, senior director of clinical research at Merck Research Laboratories, North Wales, Pa., and his associates enrolled 66 children aged 6-14 years with pre-exercise forced expiratory volume in 1 second (FEV₁) of 70% predicted or greater and a maximum fall in FEV₁ of 20% or greater at two screening exercise challenges performed on a treadmill. Study participants were randomized to receive single-dose montelukast (4 or 5 mg) or placebo before the exercise challenges were performed at 2 and 24 hours post dose.

The primary end point was maximum percent fall in FEV₁ after exercise challenge 2 hours post dose. Secondary end points included maximum percent fall in FEV₁ after the 24-hour postdose challenge and each of the following end points at 2 and 24 hours post dose: maximum percent fall in FEV₁ categorized as less than 10%, 10%-20%, and greater than 20%; area under the curve during the 60 minutes post challenge; and time to recovery to within 5% of pre-exercise baseline.

The mean age of patients was 11 years, and 56% were male. About three-quarters (74.2%) were white, 16.7% were black, and 9.1% were from other ethnic groups.

Dr. Philip reported that the mean percent fall in FEV₁ was significantly better after the 2-hour postdose exercise challenge in the montelukast treatment group, compared with the placebo group (15.3% vs. 20%, respectively). Patients in the montelukast group also fared significantly better, compared with their counterparts in the placebo group, in maximum percent fall in FEV₁ after the 24-hour postdose exercise challenge (12.92% vs. 17.25%, respectively); the categorized maximum percent fall at 2 hours (P = .034) though not at 24 hours (P = .061); and area under the curve at 2 hours (P = .022) and 24 hours (P = .013).

There were few clinical adverse events and no serious drug-related adverse events.

Dr. Philip acknowledged that the controlled laboratory setting in which the exercise challenge took place is a limitation of the study. "Natural exercise may be different from what we did in the laboratory, where all the kids had to run on a treadmill and reach a certain heart rate so we could define a clear and reproducible exercise-induced response," he explained. "Based on that response to challenge, we showed a benefit. But the kind of exercise that’s done in a laboratory may or may not match what’s done in other settings. Also, because the use of a single dose of montelukast to prevent exercise-induced bronchoconstriction in children less than age 15 years is not currently approved by the FDA, this use is considered investigational."

Merck funded the study. Dr. Philip is a full-time employee of the company.

SAN FRANCISCO – Compared with placebo, a single dose of montelukast attenuated exercise-induced bronchoconstriction in children within 2 hours and lasted through 24 hours post dose, results from a small study found.

Although this treatment effect of montelukast has been observed in previously published studies of adults with exercise-induced bronchoconstriction, this is the first analysis of its kind in children with the condition.

"The ability to take a single tablet and have it last for 24 hours is probably more meaningful for children than for adults, because children often engage in unplanned physical activities more than adults do," Dr. George Philip said in an interview during a poster session at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In a multicenter study, Dr. Philip, senior director of clinical research at Merck Research Laboratories, North Wales, Pa., and his associates enrolled 66 children aged 6-14 years with pre-exercise forced expiratory volume in 1 second (FEV₁) of 70% predicted or greater and a maximum fall in FEV₁ of 20% or greater at two screening exercise challenges performed on a treadmill. Study participants were randomized to receive single-dose montelukast (4 or 5 mg) or placebo before the exercise challenges were performed at 2 and 24 hours post dose.

The primary end point was maximum percent fall in FEV₁ after exercise challenge 2 hours post dose. Secondary end points included maximum percent fall in FEV₁ after the 24-hour postdose challenge and each of the following end points at 2 and 24 hours post dose: maximum percent fall in FEV₁ categorized as less than 10%, 10%-20%, and greater than 20%; area under the curve during the 60 minutes post challenge; and time to recovery to within 5% of pre-exercise baseline.

The mean age of patients was 11 years, and 56% were male. About three-quarters (74.2%) were white, 16.7% were black, and 9.1% were from other ethnic groups.

Dr. Philip reported that the mean percent fall in FEV₁ was significantly better after the 2-hour postdose exercise challenge in the montelukast treatment group, compared with the placebo group (15.3% vs. 20%, respectively). Patients in the montelukast group also fared significantly better, compared with their counterparts in the placebo group, in maximum percent fall in FEV₁ after the 24-hour postdose exercise challenge (12.92% vs. 17.25%, respectively); the categorized maximum percent fall at 2 hours (P = .034) though not at 24 hours (P = .061); and area under the curve at 2 hours (P = .022) and 24 hours (P = .013).

There were few clinical adverse events and no serious drug-related adverse events.

Dr. Philip acknowledged that the controlled laboratory setting in which the exercise challenge took place is a limitation of the study. "Natural exercise may be different from what we did in the laboratory, where all the kids had to run on a treadmill and reach a certain heart rate so we could define a clear and reproducible exercise-induced response," he explained. "Based on that response to challenge, we showed a benefit. But the kind of exercise that’s done in a laboratory may or may not match what’s done in other settings. Also, because the use of a single dose of montelukast to prevent exercise-induced bronchoconstriction in children less than age 15 years is not currently approved by the FDA, this use is considered investigational."

Merck funded the study. Dr. Philip is a full-time employee of the company.