A placebo-controlled, dose-ranging study of montelukast, a cysteinyl leukotriene–receptor antagonist,☆☆,,★★,

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Abstract

Background: The cysteinyl leukotrienes are important mediators of bronchial asthma. The clinical effect of montelukast, a potent cysteinyl leukotriene–receptor antagonist, was investigated in a randomized, placebo-controlled, multicenter, parallel-group, dose-ranging study.

Methods: After a 3-week, single-blind, placebo run-in period, 343 asthmatic patients (FEV1 40% to 80% of the predicted value with an improvement in FEV1 of at least 15% [absolute value] after receiving inhaled β-agonists on at least two occasions) were randomly assigned to one of six treatment groups: placebo; 10, 100, or 200 mg once daily montelukast in the evening; or 10 or 50 mg twice daily montelukast for a 6-week, double-blind treatment period followed by a 1-week placebo washout period. All patients used inhaled, short-acting β-agonists as needed.

Results: All montelukast doses caused similar and significant differences compared with placebo in asthma control endpoints. The least-square mean difference between pooled montelukast groups and placebo in the percentage change from baseline in morning FEV1 (10.30%; 95% CI: 5.56 to 15.04), as-needed β-agonist use (–0.98 puffs; 95% CI: –1.53 to –0.44), morning peak expiratory flow rate (18.80 L/min; 95% CI: 8.62 to 28.98), physicians’ and patients’ global evaluations, and asthma-specific quality-of-life scores were all significant (p ≤ 0.050). The incidence of adverse experiences was not dose related and was similar between placebo and montelukast treatment.

Conclusion: Montelukast caused a significant improvement in chronic asthma at an oral, once daily evening dose as low as 10 mg. (J Allergy Clin Immunol 1998;102:50-6.)

Section snippets

Patients

Healthy, nonsmoking (for longer than 1 year) patients with chronic asthma (men and women of nonchildbearing potential) 18 to 65 years of age were enrolled in the study. Eligible patients were required to demonstrate an FEV1 between 40% and 80% of the predicted value (withholding short-acting, inhaled β2-adrenergic agonist for 6 hours) and reversible airways obstruction (an increase in FEV1 absolute value of 15% or greater) 20 to 30 minutes after inhalation of β–agonist at least twice each

Patients

Three hundred forty-three patients (285 receiving montelukast and 58 receiving placebo) entered the active, double-blind treatment period. Of these, 307 (90%) completed active treatment and 299 (87%) completed the placebo washout period. In general, discontinuations were more frequent in the placebo group (11 [19%]) than in the pooled montelukast group (33 [12%]). There were no clinically meaningful differences between the treatment groups in demographic parameters or baseline characteristics (

DISCUSSION

Montelukast improved asthma control over a 6-week treatment period; however, a relationship between daily dose of montelukast (10 to 200 mg), dosing interval (once daily versus twice daily), and clinical efficacy parameters was not observed in this study. The similarity of response between once daily and twice daily administration and the persistent effect throughout the once daily dosing regimen demonstrated that twice daily dosing provided no additional benefit to that of once daily

Acknowledgements

We thank the members of the Montelukast Asthma Study Group: Donald Aaronson, MD; Leonard C. Altman, MD; David Appel, MD; Kathryn Blake, PharmD; Milan L Brandon, MD; Edwin Bronsky, MD; William Busse, MD; Paul Chervinsky, MD; Robert J. Dockhorn, MD; John Georgitis, MD; Thomas B. Edwards, MD; Leslie Hendeles, PharmD; Philip E. Korenblat, MD; F. Gilbert McMahon, MD; Zev B. Munk, MD; John Murray, MD; Michael J. Noonan, MD; Jacob L. Pinnas, MD; Bruce Prenner, MD; Allen Segal, MD; James Seltzer, MD;

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  • Cited by (0)

    From athe University of Washington, Seattle; bBreco Research, Houston; cThe Clinical Research Institute, San Diego; and dMerck Research Laboratories, Rahway.

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    Supported by a grant from Merck Research Laboratories

    The members of the Montelukast Asthma Study Group are listed in the acknowledgments.

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    Reprint requests: Theodore F. Reiss, MD, Merck Research Laboratories, PO Box 2000, RY 33-648, Rahway, NJ 07065.

    0091-6749/98 $5.00 + 0 1/1/90846

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