SALT LAKE CITY — A controlled-release formulation of the oral 5-lipoxygenase inhibitor zileuton proved safe and effective in asthma patients in a pivotal phase III clinical trial, Dr. Leonard Bielory reported at the annual meeting of the American College of Chest Physicians.
Zileuton is available only in an immediate-release formulation marketed as Zyflo, dosed at 600 mg four times daily. Zileuton controlled-release (CR) will offer the greater convenience of b.i.d. dosing, noted Dr. Bielory, professor of medicine at New Jersey Medical School, Newark.
The double-blind study involved 613 patients with chronic asthma at 76 U.S. sites who were randomized to 12 weeks of zileuton CR tablets at 1,200 mg b.i.d., zileuton, or placebo.
From a mean baseline forced expiratory volume in 1 second (FEV1) of 58.5% predicted, FEV1 rose by 4% in patients on zileuton CR, significantly better than with placebo.
In terms of safety end points, the most significant finding was that alanine transaminase elevations of at least three times the upper limit of normal occurred in 2.5% of patients on zileuton CR, 2.1% on zileuton, and 0.5% on placebo. In all cases, the abnormal liver function tests resolved while patients remained on their study drug or within 43 days of its discontinuation.
The incidence of all other adverse events in the zileuton CR group was similar to placebo.
Zileuton, the only 5-lipoxygenase inhibitor approved by the Food and Drug Administration, is contraindicated in patients with active liver disease or baseline elevated liver function tests. The product labeling recommends periodic liver function testing. Critical Therapeutics, the study sponsor, filed for marketing approval of zileuton CR with the FDA last summer.