Safety Study of Zileuton Injection in Patients With Asthma

September 24, 2007 updated by: Critical Therapeutics

Assessment of Safety, Tolerability, and Pharmacokinetics of Zileuton Injection in Patients With Asthma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment

60

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Huntington Beach, California, United States, 92647
        • Allergy & Asthma Specialist Medical Group
      • San Diego, California, United States, 92123
        • Allergy and Asthma Medical Group and Research Center
    • Colorado
      • Englewood, Colorado, United States, 80112
        • Colorado Allergy and Asthma Centers, PC
    • Massachusetts
      • North Dartmouth, Massachusetts, United States, 02747
        • Northeast Medical Research Associates
    • Minnesota
      • Minneapolis, Minnesota, United States, 55402
        • Clinical Research Institute
    • Missouri
      • St. Louis, Missouri, United States, 63141
        • The Clinical Research Center, L.L.C.
    • New Jersey
      • Skillman, New Jersey, United States, 08558
        • Princeton Center for Clinical Research
    • Ohio
      • Cincinnati, Ohio, United States, 45231
        • Bernstein Clinical Research Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Allergy Associates Research Center
    • Texas
      • El Paso, Texas, United States, 79902
        • Western Sky Medical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
Spirometry through 10 hours post-injection
Peak expiratory flow rates through 20 min. post-injection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Critical Therapeutics

Investigators

  • Study Director: Dana Hilt, MD, Critical Therapeutics Incorporated

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Study Completion

June 1, 2006

Study Registration Dates

First Submitted

March 2, 2006

First Submitted That Met QC Criteria

March 2, 2006

First Posted (ESTIMATE)

March 6, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

September 26, 2007

Last Update Submitted That Met QC Criteria

September 24, 2007

Last Verified

September 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTI-04-C05-201

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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