PURPOSE: To assess the safety and tolerability of zileuton, a 5-lipoyxgenase (5-LO) inhibitor currently available in an immediate-release (IR) formulation, when given as controlled-release (CR) tablets twice a day (BID) in chronic asthmatics.
METHODS: This 16-week, randomized, double-blind, multicenter, placebo-controlled study examined the efficacy and safety of zileuton CR tablets, an investigational drug, or placebo CR in 786 asthma patients. Following a 14-day two-arm placebo lead-in period, patients were randomized to one of four arms: 12 weeks of either zileuton CR 1200 mg BID versus placebo CR, or, as a benchmark comparator, zileuton IR 600 mg QID versus placebo IR, with a subsequent two-week run-out period in each arm. Safety was assessed by reported adverse events, laboratory tests, physical examination, and vital signs. Efficacy variables included forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF), as well as beta-agonist use, acute asthma exacerbations, daily and nocturnal symptoms, and quality-of-life (QOL).
RESULTS: Patients enrolled had a mean baseline percent predicted FEV1 of 58.5%. Five patients (2.5%) on zileuton CR, 2 patients (2.1%) on zileuton IR, and 1 patient (0.5%) on placebo developed alanine transaminase (ALT) elevations of ≥3 times upper limit of normal (ULN). All ALT elevations resolved (<2X ULN) while patients continued to receive study drug or within 43 days of discontinuation of treatment. The overall incidence of adverse events (AEs) reported in this study was similar in all treatment groups. There were no clinically relevant differences between treatment groups in laboratory assessments, physical examinations, or vital signs.
CONCLUSION: Results of this study suggest that zileuton CR tablets 1200 mg BID, the investigational drug, is generally well-tolerated in patients with chronic asthma.
CLINICAL IMPLICATIONS: Zileuton CR, in a BID formulation, appears to have a safety profile that may support its use in patients with persistent asthma who have no history of hepatic conditions or elevated transaminases.
DISCLOSURE: Leonard Bielory, Product/procedure/technique that is considered research and is NOT yet approved for any purpose, Zileuton CR tablets.