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

March 3, 2008 updated by: National Institute of Neurological Disorders and Stroke (NINDS)

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

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, pulse, temperature, breathing rate) and a brief physical examination to check for drug side effects from the start of drug therapy on day 2 until at least 43 hours after the last dose on day 4.

Patients who experience no difficulties are discharged from the hospital after the sixth day with a 1-month supply of medication to take 3 times a day at home. They are contacted by phone every 2 weeks while taking the medication to check side effects. Blood tests are also done every 2 weeks to check for any abnormalities.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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 outpatient basis for 1 month to determine long-term tolerability and compliance. Outpatients will be followed through phone interviews by the NIH research team along with routine blood work every 2 weeks. Our secondary objective is to document the pharmacokinetics, specifically the apparent distribution volume (Vd), elimination half-life (t1/2), elimination clearance (CLE), and steady-state concentrations (CSS) of idebenone during the inpatient phase of the study.

Outcome Parameters: Outcomes in this phase I trial are types and frequency of adverse events, if any, and compliance with the dosing regimen. Our secondary endpoint is pharmacokinetics of this dosing regimen.

Future Directions: We hope to follow these phase I studies with a multicenter, double-blinded, placebo-controlled phase III trial using an ataxia scale developed for FRDA as the primary endpoint.

Study Type

Interventional

Enrollment

16

Phase

  • 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
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institute of Neurological Disorders and Stroke (NINDS)

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

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

Diagnosis of FRDA with confirmed FRDA mutations.

Age greater than or equal to five years.

No exposure to idebenone or coenzyme Q(10) for a period of at least one week before onset of the medication phase of the study.

Written, informed consent (and assent, if applicable).

EXCLUSION CRITERIA:

History of hypersensitivity reaction to idebenone or coenzyme Q(10).

Pregnant or lactating women. All women of child-bearing potential must have negative serum pregnancy prior to the medication phase of the study. If a minor has a positive pregnancy test, we will inform her but not inform her parents unless we are asked to by the minor.

Lactose intolerant individuals (because of the lactose content in the tablet ingredients).

Age less than five years old.

Platelet count, lymphocyte count or hemoglobin below the lower limit of normal.

Alkaline phosphatase, SGOT, or SGPT greater than 1.5 x the upper limit of normal. Bilirubin greater than 1.2 g/dl.

Creatinine greater than 1.5 x the upper limit of normal.

Clinically significant medical disease that, in the judgment of the investigators, would expose the patient to undue risk of harm or prevent the patient from completing 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

Collaborators and Investigators

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

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

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

February 1, 2004

Study Completion

April 1, 2006

Study Registration Dates

First Submitted

February 27, 2004

First Submitted That Met QC Criteria

February 27, 2004

First Posted (ESTIMATE)

March 1, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

April 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 040129
  • 04-N-0129

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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