Zileuton CR vs Placebo in Poorly Controlled Asthma Patients on Moderate Dose ICS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00486343
Recruitment Status : Terminated (Slower than anticipated enrollment)
First Posted : June 14, 2007
Last Update Posted : April 3, 2008
Information provided by:
Critical Therapeutics

Brief Summary:

Asthma is a chronic inflammatory disorder of the airways with a variety of inflammatory processes contributing to the pathogenesis. The inflammation leads to a state of increased airway responsiveness and reversible airway obstruction that causes the recurrent symptoms of asthma. Despite the variety of treatments available for asthma, none are curative, and the disease continues to place a burden on society in terms of morbidity, reduced quality of life (QOL), and ever increasing healthcare costs. The prevalence of asthma continues to increase with current data suggesting that since 1980, adult asthma cases have increased by 75% and in children under 5 years of age the prevalence has increased by 160%.1 Additionally, studies have suggested that the disease severity has been underestimated and that more patients may be classified as having moderate to severe persistent disease.2 Inhaled corticosteroids (ICS) have been the cornerstone of anti-inflammatory treatment for decades and have been shown to improve lung function, decrease symptoms, and reduce asthma exacerbations.3 However, many patients are still inadequately controlled despite treatment according to current asthma management guidelines and have a significant unmet medical need. Such patients are at high risk of serious exacerbations and asthma-related mortality.4 Combining long-acting β2-agonists (LABAs) with low dose ICS has been shown to improve asthma control over using higher doses of ICS alone. However, LABAs act mainly at the bottom of the inflammatory cascade and there are concerns that they may mask underlying inflammation.5 Recently, leukotriene receptor antagonists have been added to ICS as second-line therapy in the management of asthma. Zileuton has been extensively studied in inflammatory diseases such as asthma, in which leukotrienes mediate inflammation.

The aim of this study is to assess the effect of zileuton controlled-release (CR; 1200 mg 2-times daily [BID]) on pulmonary function, asthma control, and symptomatic response in adult patients with asthma poorly controlled on moderate dose ICS.

Condition or disease Intervention/treatment Phase
Asthma Drug: Zileuton CR Drug: Placebo Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo Controlled Study of Zileuton CR Tablets Versus Placebo in Adult Patients With Poorly Controlled Asthma Patients on Moderate Dose Inhaled Corticosteroids (ICS)
Study Start Date : July 2007
Estimated Primary Completion Date : May 2008
Estimated Study Completion Date : June 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Zileuton
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1
Zileuton CR
Drug: Zileuton CR
Zileuton CR tablets 2x600mg BID for 24 weeks
Other Name: ZYFLO CR
Placebo Comparator: 2
Drug: Placebo
Placebo tablets 2x600mg BID for 24 weeks

Primary Outcome Measures :
  1. Pulmonary function measures [ Time Frame: 3 and 6 months ]

Secondary Outcome Measures :
  1. Asthma exacerbations, ACQ, AQLQ, safety [ Time Frame: 3 and 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female 12-70 years of age (inclusive).
  2. Diagnosis of asthma for at least 6 months.
  3. Morning FEV1 of 40-80% normal.
  4. Demonstrated reversible airflow restriction.
  5. Non-smokers.
  6. On moderate doses of ICS with inadequate asthma control.
  7. Signed ICF

Exclusion Criteria:

  1. Diagnosis of COPD.
  2. Uncontrolled systemic illness.
  3. Hypersensitivity to any component of ZYFLO CR
  4. Any patient with an unscheduled visit to an ER or hospital for asthma exacerbation within past 3 months.
  5. History of hepatitis or active liver disease.
  6. ALT greater than 3xULN.
  7. History of HIV infection
  8. Recent history of drug or alcohol abuse.
  9. Oral corticosteroids within one month, cromolyn sodium or nedocromil within 14 days, theophylline, LABA, ZYFLO, or leukotriene modifiers, warfarin or propranolol, inhaled anti-cholinergics, or combination LABA/ICS.
  10. Omalizumab within 3 months.
  11. Pregnant female.
  12. Participation with 30 days in investigational study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00486343

United States, Massachusetts
Critical Therapeutics
Lexington, Massachusetts, United States, 02421
Sponsors and Collaborators
Critical Therapeutics
Study Director: Cornelis Wortel, MD, PhD Critical Therapeutics/Clinquest Inc

Additional Information:
Responsible Party: Cornelis Wortel MD PhD/Acting CMO, Critical Therapeutics/Clinquest Inc Identifier: NCT00486343     History of Changes
Other Study ID Numbers: CTI-03-C07-401
First Posted: June 14, 2007    Key Record Dates
Last Update Posted: April 3, 2008
Last Verified: April 2008

Keywords provided by Critical Therapeutics:
5-LO Inhibition
Asthma control
Asthma exacerbations

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Lipoxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents
Antisickling Agents
Nucleic Acid Synthesis Inhibitors