Safety Study of Zileuton Injection in Patients With Asthma
Status:
Completed
Trial end date:
2006-06-01
Target enrollment:
Participant gender:
Summary
The prevalence of asthma continues to increase. Despite the large number of available
therapies, many patients continue to require emergency deparment (ED) visits and intensive
therapy. However, ED visits continue to be a major contributor to the healthcare cost of
asthma treatment. In the United States alone, asthma is the 11th most common reason for ED
visits, with ED visits and hospitalizations accounting for almost 50% of the healthcare cost
for asthma. Additionally, while only 20% of asthmatics have had ED visits or
hospitalizations, these patients account for over 80% of the direct costs for asthma
treatment. Current National Asthma Education and Prevention Program (NAEPP) guidelines
regarding management of acute asthma exacerbations in the ED setting include: oxygenation for
most patients, inhaled short-acting β2-agonists and systemic corticosteroids.
Zileuton, a specific 5-lipoxygenase inhibitor, has been extensively studied in inflammatory
diseases such as asthma, which involve leukotrienes as mediators of inflammation. Zileuton
Immediate Release (IR) tablets (Zyflo®) were approved by the Food and Drug Administration
(FDA) in December 1996 for the prevention and treatment of asthma in adults and children 12
years of age and older. The results of the 2 pivotal studies in asthmatics with zileuton IR
tablets demonstrated that zileuton at a dose of 600 mg QID produced and maintained a lasting
improvement of lung function. In addition to the lasting effect of zileuton, an acute
bronchodilation (as early as 60 minutes) was observed after administration of the first 600
mg oral dose.
This acute bronchodilator effect may benefit patients during an acute exacerbation of asthma
when added to the usual care in the ED or clinic setting. Critical Therapeutics has developed
an injectable formulation of zileuton that will be explored for use in acute asthma
exacerbations. This initial study is intended to provide PK data, information on safety and
tolerability and some indication of pharmacologic activity as evidenced by lung function
changes. In an attempt to enhance the potential for observing effects on lung function, only
those patients with a demonstrated ability to respond by an increase in FEV1 of at least 10%
within 3 hours after oral zileuton dosing will be enrolled.