Safety Study of Zileuton Injection in Patients With Asthma

This study has been completed.
Sponsor:
Information provided by:
Critical Therapeutics
ClinicalTrials.gov Identifier:
NCT00299065
First received: March 2, 2006
Last updated: September 24, 2007
Last verified: September 2007
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Zileuton injection
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Assessment of Safety, Tolerability, and Pharmacokinetics of Zileuton Injection in Patients With Asthma

Resource links provided by NLM:


Further study details as provided by Critical Therapeutics:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • Spirometry through 10 hours post-injection
  • Peak expiratory flow rates through 20 min. post-injection

Estimated Enrollment: 60
Study Start Date: January 2006
Estimated Study Completion Date: June 2006
  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Inhaled or oral steroids not stable for at least 1 month
  • Theophylline, cromolyn, or nedocromil within 7 days of screening
  • Leukotriene receptor agonists within 7 days of screening
  • Warfarin, propranolol, inhaled or sytemic anticholinergics within 7 days of screening
  • Long acting beta agonist within 7 days of screening
  • Oral beta-2 agonists within 12 hours of screening
  • Immunotherapy injections not in a stable dosing phase
  • Female patient who is pregnant or breast-feeding or plans to become pregnant during the study period
  • Participation in another research study within 30 days of screening
  • Patient is the Investigator or other staff or relative who is directly involved in the conduct of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00299065

Locations
United States, California
Allergy & Asthma Specialist Medical Group
Huntington Beach, California, United States, 92647
Allergy and Asthma Medical Group and Research Center
San Diego, California, United States, 92123
United States, Colorado
Colorado Allergy and Asthma Centers, PC
Englewood, Colorado, United States, 80112
United States, Massachusetts
Northeast Medical Research Associates
North Dartmouth, Massachusetts, United States, 02747
United States, Minnesota
Clinical Research Institute
Minneapolis, Minnesota, United States, 55402
United States, Missouri
The Clinical Research Center, L.L.C.
St. Louis, Missouri, United States, 63141
United States, New Jersey
Princeton Center for Clinical Research
Skillman, New Jersey, United States, 08558
United States, Ohio
Bernstein Clinical Research Center
Cincinnati, Ohio, United States, 45231
United States, Oregon
Allergy Associates Research Center
Portland, Oregon, United States, 97213
United States, Texas
Western Sky Medical Research
El Paso, Texas, United States, 79902
Sponsors and Collaborators
Critical Therapeutics
Investigators
Study Director: Dana Hilt, MD Critical Therapeutics Incorporated
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00299065     History of Changes
Other Study ID Numbers: CTI-04-C05-201
Study First Received: March 2, 2006
Last Updated: September 24, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by Critical Therapeutics:
Asthma, bronchial
Asthma, exercise-induced
Anti-asthmatic agents

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Zileuton
Anti-Asthmatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Lipoxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Central Nervous System Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on July 29, 2014