The efficacy and tolerability of MK-0633, a 5-lipoxygenase inhibitor, in chronic asthma

Respir Med. 2012 Jan;106(1):34-46. doi: 10.1016/j.rmed.2011.08.019. Epub 2011 Sep 25.


Leukotriene B4 (LTB(4)) is a potent inflammatory mediator in asthma, and is increased in more severe asthma. Targeting LTB(4), in addition to cysteinyl leukotrienes, could be beneficial in asthma. This was a randomized, double-blind trial of once-daily MK-0633, a potent 5-lypoxygenase inhibitor, 10 mg, 50 mg, and 100 mg, and placebo in patients 18-70 years with a history of chronic asthma, and FEV(1) ≥45 and ≤85% predicted. There was a 6-week main period and optional 18-week and 34-week periods (52 weeks total), the latter two comparing only MK-0633 100 mg and placebo. The primary endpoint was the change from baseline in FEV(1) over the last 4 weeks of the 6-week primary treatment period. Secondary endpoints included symptom scores, β-agonist use, peak expiratory flow (PEF), asthma quality of life questionnaire (AQLQ), asthma control questionnaire (ACQ), asthma attacks, exacerbations, days with asthma control, post-β-agonist FEV(1), and blood eosinophils. MK-0633 100 mg was significantly more effective than placebo for the change from baseline in FEV(1) (0.20 L vs. 0.13 L; p = 0.004). The other MK-0633 doses were not significantly more effective than placebo. MK-0633 (at various doses) was also more effective than placebo for β-agonist use, AQLQ, AM and PM PEFR, ACQ, and post-β-agonist FEV(1) (p < 0.05 for all). MK-0633 was associated with a dose-dependent increase in elevated aspartate aminotransferase and alanine aminotransferase. Because of the relative benefit-risk ratio, the optional study periods were terminated after unblinding for the main study period. Overall, the benefit-risk ratio did not support the clinical utility of MK-0633 in asthma.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asthma / blood
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Benzenesulfonates / therapeutic use*
  • Benzopyrans / therapeutic use*
  • Chronic Disease
  • Disease Progression
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Leukotriene B4 / agonists*
  • Lipoxygenase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Oxadiazoles / therapeutic use*
  • Spirometry / methods*
  • Treatment Outcome
  • Young Adult


  • Benzenesulfonates
  • Benzopyrans
  • Lipoxygenase Inhibitors
  • MK-0633 p-toluenesulfonate
  • Oxadiazoles
  • Leukotriene B4