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Analysis of behavior-related adverse experiences in clinical trials of montelukast

      Background

      Frequencies of behavior-related adverse experiences (BRAEs) in controlled clinical studies of leukotriene modifier drugs have not been summarized.

      Objective

      We sought to compare the frequency of BRAEs in patients receiving montelukast or placebo in a retrospective analysis of Merck clinical trial data.

      Methods

      An adverse experience database was constructed to include all double-blind, placebo-controlled trials of montelukast meeting prespecified criteria. BRAEs (described using the Medical Dictionary for Regulatory Activities controlled vocabulary dictionary) were prespecified to include any term in the Psychiatric Disorders System Organ Class, selected terms related to general disorders, and terms related to akathisia. Frequencies of BRAEs (overall, leading to study discontinuation, and/or serious) were summarized. Analyses estimated the odds ratios (ORs) for montelukast versus placebo based on the frequency of patients with BRAEs in each study.

      Results

      In total 35 adult and 11 pediatric placebo-controlled trials were included; 11,673 patients received montelukast, 8,827 received placebo, and 4,724 received active control. The frequency of patients with 1 or more BRAEs was 2.73% and 2.27% in the montelukast and placebo groups, respectively; the OR for montelukast versus placebo was 1.12 (95% CI, 0.93-1.36). The frequency of patients with a BRAE leading to study discontinuation was 0.07% and 0.11% in the montelukast and placebo groups, respectively (OR, 0.52; 95% CI, 0.17-1.51). The frequency of patients with a BRAE considered serious was 0.03% in both treatment groups.

      Conclusion

      Reports of BRAEs were infrequent in clinical trials of montelukast. Those leading to study discontinuation or considered serious were rare. Frequencies were similar regardless of treatment group.

      Key words

      Abbreviations used:

      AE (Adverse experience), Akath-PT (Akathisia-related preferred term), BRAE (Behavior-related adverse experience), CNS (Central nervous system), CysLT1, (Cysteinyl leukotriene type 1), CysLT (Cysteinyl leukotriene), FDA (US Food and Drug Administration), HLGT (High-level Group Term), MedDRA (Medical Dictionary for Regulatory Activities), OR (Odds ratio), OtherSelect-PT (Other selected behavior-related preferred term), PT (Preferred Term), Psych-SOC (Psychiatric Disorders System Organ Class), SMQ (Standardized MedDRA query), SOC (System Organ Class)
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      • Correction
        Journal of Allergy and Clinical ImmunologyVol. 125Issue 5
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          With regard to the October 2009 article entitled “Analysis of behavior-related adverse experiences in clinical trials of montelukast” (J Allergy Clin Immunol 2009;124:699-706), two protocol numbers in Table E1 are incorrect as given. Under “Adult Studies,” protocol number “202” should read “A202,” and protocol number “402” should read “A402.”
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