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A Study of Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia (FRDA) Patients (MICONOS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Santhera Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00905268
First received: May 19, 2009
Last updated: May 19, 2016
Last verified: May 2016
History of Changes
Results First Received: October 20, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Friedreich's Ataxia
Interventions: Drug: idebenone
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Group A: Idebenone

Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Group B: Idebenone

Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
C: Idebenone

Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
D: Placebo

placebo

Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

Participant Flow:   Overall Study
    Group A: Idebenone   Group B: Idebenone   C: Idebenone   D: Placebo
STARTED   57   57   59   59 
COMPLETED   53   56   59   57 
NOT COMPLETED   4   1   0   2 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Group A: Idebenone

Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Group B: Idebenone

Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
C: Idebenone

Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
D: Placebo

placebo

Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Total Total of all reporting groups

Baseline Measures
   Group A: Idebenone   Group B: Idebenone   C: Idebenone   D: Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 57   57   59   59   232 
Age 
[Units: Years]
Mean (Standard Deviation) 		 30.9  (13.7)   31.6  (13.1)   30.9  (13.6)   30.4  (13.3)   30.9  (13.3) 
Gender 
[Units: Participants]
 		         
Female   23   25   27   32   107 
Male   34   32   32   27   125 
Region of Enrollment [1] 
[Units: Participants]
 		         
Germany   40   41   39   36   156 
United Kingdom   4   6   6   5   21 
Austria   2   4   2   5   13 
Belgium   3   1   5   4   13 
France   5   2   4   6   17 
Netherlands   3   3   3   3   12 
[1] The Intent-To-Treat (ITT) population included all randomized subjects who received at least one dose of the study medication and had a confirmed diagnosis of FRDA, did not take idebenone within one month pre-Screening or between Screening and Visit 1, and were not under idebenone treatment at Baseline according to available PK results at Visit 1. The subjects were analyzed as randomized regardless of protocol deviations


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52   [ Time Frame: Baseline and week 52 ]

Measure Type Primary
Measure Title Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52
Measure Description The International Cooperative Ataxia Rating Scale (ICARS) is a commonly used evaluation and is composed of four clinical sub-scores involving the following: posture and gait, limb coordination, speech and oculomotor function.The ICARS score is the total sum of the sub scores and ranges from 0 to 100, with 100 indicative of the most severely affected outcome.
Time Frame Baseline and week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Intent-To-Treat (ITT) population included all randomized subjects who received at least one dose of the study medication and had a confirmed diagnosis of FRDA, did not take idebenone within one month pre-Screening or between Screening and Visit 1, and were not under idebenone treatment at Baseline according to available PK results at Visit 1.

Reporting Groups
  Description
Group A: Idebenone

Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Group B: Idebenone

Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
C: Idebenone

Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
D: Placebo

placebo

Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

Measured Values
   Group A: Idebenone   Group B: Idebenone   C: Idebenone   D: Placebo 
Participants Analyzed 
[Units: Participants]
 		 55   55   59   58 
Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52 
[Units: Units on a scale]
Mean (Standard Deviation) 		 1.6  (5.85)   1.7  (6.64)   1.2  (5.22)   1.1  (6.76) 

No statistical analysis provided for Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52



2.  Secondary:   Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52   [ Time Frame: Baseline and week 52 ]

Measure Type Secondary
Measure Title Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52
Measure Description The Friedreich Ataxia Rating Scale (FARS) is made up of a measure of ataxia, and activities of daily living subscale and a neurological subscale. The scores from the three subscales are added to generate a total score ranging from 0 to 159, with a higher score indicating a greater level of disability.
Time Frame Baseline and week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The comparison was carried out in the ITT population, on data imputed using the last observation carried forward (LOCF) method.

Reporting Groups
  Description
Group A: Idebenone

Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Group B: Idebenone

Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
C: Idebenone

Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
D: Placebo

placebo

Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

Measured Values
   Group A: Idebenone   Group B: Idebenone   C: Idebenone   D: Placebo 
Participants Analyzed 
[Units: Participants]
 		 54   54   59   58 
Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52 
[Units: Units on a scale]
Mean (Standard Deviation) 		 0.9  (7.19)   1.2  (5.24)   1.4  (5.60)   0.9  (6.77) 

No statistical analysis provided for Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52



3.  Secondary:   Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin   [ Time Frame: week 52 ]

Measure Type Secondary
Measure Title Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin
Measure Description

The International Cooperative Ataxia Rating Scale (ICARS) is a commonly used evaluation and is composed of four clinical sub-scores involving the following: posture and gait, limb coordination, speech and oculomotor function.The ICARS score is the total sum of the sub scores and ranges from 0 to 100, with 100 indicative of the most severely affected outcome.

ICARS Responder Analysis at Week 52: Percentage of subjects Improving by 2.5 Points or More.
Time Frame week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Intent-To-Treat (ITT) population included all randomized subjects who received at least one dose of the study medication and had a confirmed diagnosis of FRDA, did not take idebenone within one month pre-Screening or between Screening and Visit 1, and were not under idebenone treatment at Baseline according to available PK results at Visit 1.

Reporting Groups
  Description
Group A: Idebenone

Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Group B: Idebenone

Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
C: Idebenone

Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
D: Placebo

placebo

Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

Measured Values
   Group A: Idebenone   Group B: Idebenone   C: Idebenone   D: Placebo 
Participants Analyzed 
[Units: Participants]
 		 55   55   59   58 
Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin 
[Units: Percentage of patients]
 		 18.2   23.6   23.7   31 

No statistical analysis provided for Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin



4.  Secondary:   Proportion of Patients Improving on Left Ventricular Peak Systolic Strain Rate or Showing a Reduction in Left Ventricular Mass Index (LVMI) With no Worsening in Strain Rate   [ Time Frame: 1 year ]

Measure Type Secondary
Measure Title Proportion of Patients Improving on Left Ventricular Peak Systolic Strain Rate or Showing a Reduction in Left Ventricular Mass Index (LVMI) With no Worsening in Strain Rate
Measure Description (In the statistical analysis sub-population presenting with cardiac involvement as defined by the FRDA cardiomyopathy criteria)
Time Frame 1 year  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subgroup of subjects with cardiac involvement as defined by Friedreich’s ataxia cardiomyopathy (FRDA-CM)

Reporting Groups
  Description
Group A: Idebenone

Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Group B: Idebenone

Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
C: Idebenone

Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
D: Placebo

placebo

Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

Measured Values
   Group A: Idebenone   Group B: Idebenone   C: Idebenone   D: Placebo 
Participants Analyzed 
[Units: Participants]
 		 36   35   33   34 
Proportion of Patients Improving on Left Ventricular Peak Systolic Strain Rate or Showing a Reduction in Left Ventricular Mass Index (LVMI) With no Worsening in Strain Rate 
[Units: Percentage of patients]
 		 50   51.4   30.3   44.1 

No statistical analysis provided for Proportion of Patients Improving on Left Ventricular Peak Systolic Strain Rate or Showing a Reduction in Left Ventricular Mass Index (LVMI) With no Worsening in Strain Rate



5.  Secondary:   Change in Peak Systolic Strain Rate From Baseline to Week 52   [ Time Frame: 1 year ]

Measure Type Secondary
Measure Title Change in Peak Systolic Strain Rate From Baseline to Week 52
Measure Description Mean Change of Peak systolic longitudinal strain rate (PSLSR) from Baseline to Week 52 in subjects with cardiac involvement (FRDA-CM criteria), where positive value in PSLSR is a deterioration and negative value an improvement.
Time Frame 1 year  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Subgroup of subjects with cardiac involvement as defined by Friedreich’s ataxia cardiomyopathy (FRDA-CM)

Reporting Groups
  Description
Group A: Idebenone

Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Group B: Idebenone

Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
C: Idebenone

Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
D: Placebo

placebo

Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

Measured Values
   Group A: Idebenone   Group B: Idebenone   C: Idebenone   D: Placebo 
Participants Analyzed 
[Units: Participants]
 		 36   35   33   34 
Change in Peak Systolic Strain Rate From Baseline to Week 52 
[Units: 1/s]
Mean (Standard Deviation) 		 0.007  (0.220)   -0.004  (0.265)   0.085  (0.227)   0.024  (0.192) 

No statistical analysis provided for Change in Peak Systolic Strain Rate From Baseline to Week 52



6.  Secondary:   Change in Peak Workload From Baseline to Week 52   [ Time Frame: 1 year ]

Measure Type Secondary
Measure Title Change in Peak Workload From Baseline to Week 52
Measure Description

Assessed by a modified exercise test, in a subset of patients able to undertake this.

Wpeak has been calculated from the following formula: Workload last fully completed stage + (seconds completed in last stage / 60 * (4 [if arm ergonometry] or 10 [if leg ergonometry])).
Time Frame 1 year  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Group A: Idebenone

Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Group B: Idebenone

Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
C: Idebenone

Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day

idebenone: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
D: Placebo

placebo

Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

Measured Values
   Group A: Idebenone   Group B: Idebenone   C: Idebenone   D: Placebo 
Participants Analyzed 
[Units: Participants]
 		 55   55   59   58 
Change in Peak Workload From Baseline to Week 52 
[Units: Watts]
Mean (Standard Deviation) 		 1.15  (16.362)   -7.41  (34.499)   -6.91  (20.179)   -1.54  (16.509) 

No statistical analysis provided for Change in Peak Workload From Baseline to Week 52




  Serious Adverse Events
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  Other Adverse Events
  Show Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Prof. Nicholas William Wood
Organization: The National Hospital, University College London
phone: 020 7837 3611
e-mail: n.wood@ucl.ac.uk



Responsible Party: Santhera Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00905268     History of Changes
Other Study ID Numbers: SNT-III-001
Study First Received: May 19, 2009
Results First Received: October 20, 2015
Last Updated: May 19, 2016