Study to Assess the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia (IONIA)

• ClinicalTrials.gov Identifier: NCT00537680
• Recruitment Status: Completed
• First Posted: October 1, 2007
• Results First Posted: December 29, 2011
• Last Update Posted: February 3, 2012
• Sponsor: Santhera Pharmaceuticals
• Information provided by (Responsible Party): Santhera Pharmaceuticals

Tracking Information

• First Submitted Date: September 7, 2007
• First Posted Date: October 1, 2007
• Results First Submitted Date: June 7, 2011
• Results First Posted Date: December 29, 2011
• Last Update Posted Date: February 3, 2012
• Study Start Date: December 2007
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 22, 2011)

ICARS [ Time Frame: baseline and 6 months ]

International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. Scores for each subscale quantify the extent of ataxia in each clinically important area. Subscale scores are summed to give a total score ranging from 0 (best) to 100 (worst).

• Original Primary Outcome Measures (submitted: September 28, 2007): ICARS [ Time Frame: 6 months ]
• Change History: Complete list of historical versions of study NCT00537680 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: November 22, 2011)

• FARS [ Time Frame: 6 Months ]
  Friedreich's Ataxia Rating Scale
• ADL of FARS [ Time Frame: 6 Months ]
  ADL=Activities of Daily Living
• FACT [ Time Frame: 6 Months ]
  Friedreich's Ataxia Composite Test

Original Secondary Outcome Measures (submitted: September 28, 2007)

• FARS [ Time Frame: 6 Months ]
• ADL of FARS [ Time Frame: 6 Months ]
• FACT [ Time Frame: 6 Months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia
• Official Title: A Phase III Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients
• Brief Summary: This study is meant to assess the effectiveness of idebenone on neurological outcome measures in patients with Friedreich's Ataxia over a 6 months period.
• Detailed Description: The study involves 6 clinic visits and upon completion the possibility to join a 12 months extension study where all patients will receive high dose Idebenone.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Friedreich's Ataxia

Intervention

• Drug: Idebenone
  Patients ≤ 45 kg/99 lbs: idebenone 450 mg/day; Patients > 45 kg/99 lbs: idebenone 900 mg/day
• Drug: Idebenone
  Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day; Patients > 45 kg/99 lbs: idebenone 2250 mg/day
• Drug: Placebo
  Placebo was provided as film-coated tablets that were the same size, weight and appearance as the idebenone tablets.

Study Arms

• Experimental: 1
  mid dose Idebenone
  Intervention: Drug: Idebenone
• Experimental: 2
  high dose Idebenone
  Intervention: Drug: Idebenone
• Placebo Comparator: 3
  Intervention: Drug: Placebo

Publications *

• Meier T, Perlman SL, Rummey C, Coppard NJ, Lynch DR. Assessment of neurological efficacy of idebenone in pediatric patients with Friedreich's ataxia: data from a 6-month controlled study followed by a 12-month open-label extension study. J Neurol. 2012 Feb;259(2):284-91. doi: 10.1007/s00415-011-6174-y. Epub 2011 Jul 22.
• Lagedrost SJ, Sutton MS, Cohen MS, Satou GM, Kaufman BD, Perlman SL, Rummey C, Meier T, Lynch DR. Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA). Am Heart J. 2011 Mar;161(3):639-645.e1. doi: 10.1016/j.ahj.2010.10.038. Epub 2011 Jan 31.
• Lynch DR, Perlman SL, Meier T. A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich ataxia. Arch Neurol. 2010 Aug;67(8):941-7. doi: 10.1001/archneurol.2010.168.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 28, 2009): 70
• Original Estimated Enrollment (submitted: September 28, 2007): 51
• Actual Study Completion Date: April 2009
• Actual Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

• Documented diagnosis of Friedreich's Ataxia (FRDA) with confirmed FRDA mutations
• Patients 8 - 17 years of age at baseline
• Patients with a body weight greater than 25 kg/55 lbs at baseline
• Patients able to walk at least 10 meters without accompanying person (ICARS Walking Capacities score ≤6) at screening and baseline
• Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication
• Negative urine pregnancy test at screening and baseline (female patients of childbearing potential)

Exclusion criteria:

• Treatment with idebenone, Coenzyme Q10 or vitamin E (if taken at a dose 5 times above the daily requirement) within the past month
• Patients with International Cooperative Ataxia Rating Scale (ICARS) score of greater than 54 or less than 10 at screening
• Pregnancy and/or breast-feeding
• Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of Aspartate Aminotransferase (AST; also known as GOT), Alanine Aminotransferase (ALT; also known as GPT) or creatinine
• History of abuse of drugs or alcohol
• Participation in the previous (Phase II) study of idebenone at the National Institutes of Health (NIH)
• Participation in a trial of another investigational drug within the last 3 months

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 8 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00537680
• Other Study ID Numbers: SNT-III-002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Santhera Pharmaceuticals
• Study Sponsor: Santhera Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Principal Investigator: Susan Perlman, MD; University of California, Los Angeles
• Principal Investigator: David Lynch, MD; Children's Hospital of Philadelphia

• PRS Account: Santhera Pharmaceuticals
• Verification Date: February 2012