Trial of Zileuton CR in Children and Adults With Sickle Cell Disease

NCT01136941 | Completed Phase 1 DMC

• 1 other identifier: 2009-1622
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test the safety of Zileuton and see what effects (good and bad) it has on you, other children and adults with Sickle Cell Disease (SCD). The investigators also want to see how Zileuton is handled by your body at different doses. Zileuton is a drug that is approved by the Food and Drug Administration (FDA) for the treatment of asthma for people age 12 and older. The FDA has not approved Zileuton for the treatment of SCD, so it is being studied as an investigational drug for SCD through an application to the FDA. In asthma patients, Zileuton helps by reducing inflammation. This study will see if Zileuton helps to reduce inflammation associated with SCD.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (2)

• Adverse Event Grading as a Measure of Safety and Tolerability

  The drug will be considered safe and tolerable if there is no grade-4 toxicity and no irreversible grade-3 toxicity upon de-escalation or discontinuation. The dose for the Part 2 portion of the trial will be the dose at which there was no DLT in 5 out of 6 at highest dose level below the maximally administered dose.

  Outcome measures will be assessed at all study visits. Visits occur at week 1, Week 2, Week 4 and Week 6. Follow-up assessments will take place at Weeks 8 and 10.

• Characterization of the Distribution of Zileuton Pharmacokinetic Parameter Estimates and Drug Exposure

  We do not anticipate a difference in PK from normal controls. PK analysis will be performed to verify steady state levels of ZL and LT are similar to normal controls.

  Outcome measures will be assessed at study visits occurring at Visit 1, week 1, Week 2, Week 3 and Week 5.

Study Arms (1)

Treatment

EXPERIMENTAL

Research participants will be administered Zileuton according to the dose escalation/de-escalation schema provided in the protocol.

Drug: Zileuton

Interventions

Zileuton DRUG

Zileuton is available as a 600 mg tablet. Dosing begins at 2.4gm/day and will be increased to 3.0gm/day. Tablets will be taken twice daily for the 6 week duration of the study.

Treatment

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:

• Confirmed diagnosis of SCD (HbSS,HbSC,HBS Beta thalassemia, or HBS 0 thalassemia)
• Absence of an acute sickle event or ACS in the last 4 wks
• Not on hydroxyurea
• Ability to swallow pills
• Ability to comply with pulmonary function testing

You may not qualify if:

• History of active hepatitis
• HIV positivity
• Pregnant or nursing
• Unable to comply with contraceptive measures
• On an investigational drug within 4 weeks
• On hydroxyurea, leukotriene antagonists (e.g., Singulair) or steroids, theophylline, coumadin, terfenadine or beta-2 blockers that affect the airway: carteolol, carvedilol, labetalol, nadolol, penbutolol, pindolol, sotalol and timolol, or on propranolol for the last four weeks
• On chronic transfusion therapy
• A serious, concurrent illness that would limit ability to complete or comply with the study requirements
• Males who drink alcoholic beverages \>5-6 drinks/day or females who drink alcoholic beverages \>3-4 drinks/day

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

zileuton

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Punam Malik, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2010
• First Posted: June 4, 2010
• Study Start: September 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: June 18, 2014

Record last verified: 2014-06

Locations

US (1)