MK-0633, a potent 5-lipoxygenase inhibitor, in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is associated with neutrophil-mediated inflammation, a potential target for treatment in COPD. We evaluated MK-0633, a 5-lipoxygenase inhibitor in patients with COPD. This was a 12 week, randomized, double-blind, multicenter study comparing MK-0633 100 mg and placebo in patients 40-75 years of age (N = 266) with COPD, post-β-agonist forced expiratory volume in 1 s (FEV(1)) 25%-75% predicted, and an FEV(1)/forced vital capacity ratio (FVC) ≤ 70%. Long-acting inhaled bronchodilators were permitted for approximately 50% of patients. The primary efficacy endpoint was the change from baseline in pre-dose (trough) FEV(1) measured over the last 2 weeks of the 12 week treatment period. The change in FEV(1) over the last 2 weeks of the 12 weeks treatment period compared to baseline was 0.015 L for MK-0633 and 0.0002 for placebo (p = 0.556). For COPD Global Evaluation, 75.4% of patients receiving MK-0633 reported feeling better vs. 59.8% of patients receiving placebo (p = 0.032). There were no other significant differences between treatments. MK-0633 was well-tolerated and comparable to placebo. The 5-LO inhibitor MK-0633 was not significantly more effective than placebo in improving FEV(1) from baseline in patients with COPD, although more patients reported feeling improved with MK-0633. Clinicaltrials.gov identifier: NCT00418613.
Bernstein Allergy Group, Bernstein Clinical Research Center, Inc 8444 Winton Rd, Cincinnati, OH 45231, USA. jonathan.bernstein@uc.edu
Jonathan A
JA
Bernstein
Nancy
N
Liu
Barbara A
BA
Knorr
Steven S
SS
Smugar
William D
WD
Hanley
Theodore F
TF
Reiss
Steven
S
Greenberg
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001557:Benzenesulfonates / Q000008:administration & dosage*; D001578:Benzopyrans / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000008:administration & dosage*; D010919:Placebos; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D013147:Spirometry; D016896:Treatment Outcome
D001557:Benzenesulfonates; D001578:Benzopyrans; D001993:Bronchodilator Agents; C552157:MK-0633 p-toluenesulfonate; D010069:Oxadiazoles; D010919:Placebos