Clinical Trial: Phase 1 Trial of Idebenone to Treat Patients With Friedreich's Ataxia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase 1B Clinical Trial to Establish the Safety and Tolerability of a Multiple-Dose Regimen of Idebenone Administered to Patients With Friedreich's Ataxia

Brief Summary:

This study will determine the highest amount of idebenone that can be taken without harmful side effects in children, teenagers, and adults with Friedreich's ataxia, a progressive degenerative disease that affects several body systems. Studies in France and Canada showed that patients with Friedreich's ataxia who took idebenone had a decrease in the size of their left ventricle (main pumping chamber of the heart), which is often enlarged in this disease. It is possible that idebenone may also prevent the progression of nervous system degeneration in Friedreich's ataxia.

Patients 5 years of age and older with Friedreich's ataxia may be eligible for this study. Candidates are screened with a blood test and review of their medical records, including genetic studies.

Participants undergo the following procedures during a 6-day hospital admission to the NIH Clinical Center:

  • Placement of an intravenous catheter (plastic tube inserted into a vein) for collecting blood samples after drug administration
  • Blood and urine tests
  • Heart examination, including electrocardiogram (EKG), to assess heart function and size.
  • Idebenone therapy: Patients take three tablets a day (at 7 AM, 1 PM and 7 PM) on days 2, 3 and 4 of hospitalization. Blood samples are collected through the IV tube at 0.5, 1, 2, 4, and 6 hours after the first dose on day 2, then at 1 hour after the first and third doses every day, and then at 1, 2, 4, 8, 12, 24, 36, and 48 hours after the last dose on day 4 to determine how the body uses and eliminates the drug.
  • Monitoring for drug side effects: Patients have frequent checks of vital signs (blood pressure

    Detailed Summary:

    Background: Friedreich's ataxia (FRDA) is a progressive, autosomal recessive, multisystem degenerative disease for which there is currently no effective treatment. Recent studies have demonstrated that lipid-soluble antioxidants lead to a modest reversal of cardiomyopathy in patients with FRDA. It is possible that antioxidants may also prevent the progression of neurodegeneration.

    Objective: This will be a phase 1B, unblinded trial examining the toxicity and tolerability of the antioxidant idebenone given as a multiple-dose regimen for a short inpatient course and then long term to patients with FRDA.

    Study Population: We aim to enroll 15 patients divided evenly among three age cohorts: children (ages 5-11), adolescents (ages 12-17), and adults (age greater than or equal to 18).

    Design: Our primary objective is to examine the tolerability of idebenone given at a dose of 60 mg/kg/day for 72 hours (total of 9 doses) in an inpatient setting (NIH Clinical Center). This dose is below the maximum dose examined (75 mg/kg/day) that was well tolerated with no dose-limiting toxicity (DLT) in our phase 1A (protocol# 01-N-0167) study. The 72 hour course represents 5.5 half-lives of the drug based upon previous studies of the drug in healthy human subjects and our phase 1A data, thereby allowing the serum concentration of the drug to reach steady-state levels. This multiple dose regimen will allow us to examine accumulation of the drug and to examine tolerability of the drug at a steady-state concentration. The patients will then be followed by inpatient monitoring for an additional 43 hours, representing 3.3 half-lives, to allow relatively complete elimination of the drug. If no adverse events are noted during the inpatient phase of the trial, patients will resume taking the drug on an
    Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

    Current Primary Outcome:

    Original Primary Outcome:

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: February 27, 2004
    Date Started: February 2004
    Date Completion: April 2006
    Last Updated: March 3, 2008
    Last Verified: April 2006