Effects of montelukast (MK-0476), a new potent cysteinyl leukotriene (LTD 4) receptor antagonist, in patients with chronic asthma☆,☆☆,★,★★
Section snippets
Patients
Nonsmoking (at least 1 year, having smoked no more than 5 pack-years) male and female (without childbearing potential) patients between 18 and 55 years of age (within 15% of ideal body weight) with a history of recurring symptoms associated with asthma including dyspnea, wheezing, or cough requiring treatment for at least 1 year were eligible for study participation. Patients admitted to the study were required to have reversible airway obstruction (defined as an FEV 1 between 50% and 80% of
Patient profile
Twenty-nine asthmatic (23 male and 6 female) patients were enrolled in the trial (Table I). Twenty-eight patients completed the first treatment period (one patient discontinued for personal reasons soon after the start of the period). Twenty-seven patients entered (one patient discontinued between treatment periods because of an upper respiratory tract infection) and 25 completed the second treatment period (two patients discontinued during the second treatment period because of a rash and an
DISCUSSION
This first multiple-dose trial of montelukast (200 mg three times daily for 10 days) in patients with chronic asthma demonstrates that this orally active, potent, and selective cysteinyl LT 1 receptor antagonist improves objective and subjective measurements of asthma; compared with placebo, significant improvements in FEV 1 and daytime asthma symptoms/activity scores and a decrease in as-needed β-agonist use were observed. The improvement in the nocturnal awakening score, which favored
Acknowledgements
We thank Ms. Susan Ruffalo for editorial assistance, Ms. Nancy Noonan for study monitoring and data review, and Ms. Judy Evans for typing the manuscript.
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2018, Journal of Allergy and Clinical ImmunologyCitation Excerpt :In fact, the only published dose-ranging study of montelukast in the LTD4 provocation setting has shown progressively increasing shifts in the dose-response relation for LTD4 up to 250 mg of montelukast. It should be appreciated that montelukast is a very selective CysLT1 antagonist and that the initial clinical treatment studies used much higher doses (100-200 mg).28,29 Interestingly, lung function improvement in these high-dose studies was greater than in subsequent studies using 10 mg,30 although performed on comparable patient populations.
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2018, Prostaglandins Leukotrienes and Essential Fatty AcidsEfficacy and safety of lebrikizumab in adult patients with mild-to-moderate asthma not receiving inhaled corticosteroids
2018, Respiratory MedicineCitation Excerpt :With approximately 100 patients per arm (lebrikizumab and placebo), the study had 80% power to detect a difference in absolute change in FEV1 from baseline to Week 12 between lebrikizumab and placebo of 120 mL (approximately 5% change from baseline). Data from the montelukast treatment arm were used to evaluate the assay sensitivity of the study because montelukast-treated patients were expected to demonstrate an increase in FEV1 over the 12-week treatment period [11–13]. The standard deviation for the absolute change from baseline to Week 12 was 300 mL for both comparisons (i.e., lebrikizumab and placebo, and montelukast and placebo).
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From aDepartments of Pulmonary/Immunology and Biostatistics, Merck Research Laboratories, Rahway; bAllergy and Infectious Diseases, Pacific Medical Center, Seattle; cAllergy and Asthma Center, North Dartmouth; dDepartment of Allergy and Immunology, Creighton University School of Medicine, Omaha; and eClinical Research of the Ozarks, Inc., Rolla.
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Supported by a grant from Merck Research Laboratories.
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Reprint requests: Theodore F. Reiss, MD, Merck Research Laboratories, P.O. Box 2000, RY 33-648, Rahway, NJ 07065.
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