Safety Study of Zileuton Injection in Patients With Asthma

NCT00299065 | Completed Phase 1

• 1 other identifier: CTI-04-C05-201
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Asthma

Keywords

Asthma, bronchial; Asthma, exercise-induced; Anti-asthmatic agents

Outcome Measures

Primary Outcomes (6)

• Clinical laboratory tests through 48 hours post-injection

• Vital signs through 10 hours post-injection

• Pulse oximetry through 10 hours post-injection

• Injection site evaluations through 10 hours post-injection

• Adverse event assessments through 48 hours post-injection

• Blood samples for PK through 10 hours post-injection

Secondary Outcomes (2)

• Spirometry through 10 hours post-injection

• Peak expiratory flow rates through 20 min. post-injection

Interventions

Zileuton injection DRUG

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of asthma
• Morning FEV1 of 40-80% of predicted normal
• Evidence post-bronchodilator increase in FEV1 of at least 15%
• Evidence of at least 10% increase in FEV1 within 3 hours after oral 600 mg zileuton dose
• Signed IRB approved informed consent
• Patients must be willing and able to withhold:
• short acting β2-agonists for at least 6 hours prior to spirometry
• inhaled corticosteroids (ICS) for at least 24 hours prior to sprirometry
• long acting β2-agonists (LABA) for 7 days and be willing and able to switch from a LABA/ICS combination product to a monotherapy ICS product

You may not qualify if:

• Females of childbearing potential not using effective contracception
• Any uncontrolled systemic disease other than asthma
• Patient with known hypersensitivity to zileuton IR tablets or zileuton injection or any of the components found therein
• An upper or lower respiratory tract infection within 2 weeks of screening
• An ED visit or hospitalization for asthma within 3 months of screening
• Oral or parenteral corticosteroid use for asthma exacerbation within 3 months of screening
• Current cigarette smoker and/or \>10 pack-year smoking history
• History of hepatitis B (HBV) or hepatitis C infection or other active liver disease or chronic hepatitis
• Screening ALT \>1.5x ULN
• Patient with impaired renal function or serum creatinine \>1.5x ULN
• History of HIV infection
• History of drug or alcohol abuse within 1 year of screening
• Patient taking any of the following asthma/allergy medications:
• Anti-IgE meds within 3 months of screening
• Zileuton IR tablets within 1 month of screening

Sponsors & Collaborators

• Critical Therapeutics: lead

Study Sites (10)

Allergy & Asthma Specialist Medical Group

Huntington Beach, California, 92647, United States

Location

Allergy and Asthma Medical Group and Research Center

San Diego, California, 92123, United States

Location

Colorado Allergy and Asthma Centers, PC

Englewood, Colorado, 80112, United States

Location

Northeast Medical Research Associates

North Dartmouth, Massachusetts, 02747, United States

Location

Clinical Research Institute

Minneapolis, Minnesota, 55402, United States

Location

The Clinical Research Center, L.L.C.

St Louis, Missouri, 63141, United States

Location

Princeton Center for Clinical Research

Skillman, New Jersey, 08558, United States

Location

Bernstein Clinical Research Center

Cincinnati, Ohio, 45231, United States

Location

Allergy Associates Research Center

Portland, Oregon, 97213, United States

Location

Western Sky Medical Research

El Paso, Texas, 79902, United States

Location

Related Publications (3)

• Fuhlbrigge AL, Adams RJ, Guilbert TW, Grant E, Lozano P, Janson SL, Martinez F, Weiss KB, Weiss ST. The burden of asthma in the United States: level and distribution are dependent on interpretation of the national asthma education and prevention program guidelines. Am J Respir Crit Care Med. 2002 Oct 15;166(8):1044-9. doi: 10.1164/rccm.2107057.

  PMID: 12379546 BACKGROUND

• Colice GL, Burgt JV, Song J, Stampone P, Thompson PJ. Categorizing asthma severity. Am J Respir Crit Care Med. 1999 Dec;160(6):1962-7. doi: 10.1164/ajrccm.160.6.9902112.

  PMID: 10588614 BACKGROUND

• Rodrigo GJ, Rodrigo C, Hall JB. Acute asthma in adults: a review. Chest. 2004 Mar;125(3):1081-102. doi: 10.1378/chest.125.3.1081.

  PMID: 15006973 BACKGROUND

MeSH Terms

Conditions

Asthma; Asthma, Exercise-Induced

Interventions

zileuton

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Exercise-Induced Allergies

Study Officials

• Dana Hilt, MD

  Critical Therapeutics Incorporated

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 2, 2006
• First Posted: March 6, 2006
• Study Start: January 1, 2006
• Study Completion: June 1, 2006
• Last Updated: September 26, 2007

Record last verified: 2007-09

Locations

US (10)