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

• Sponsor: Santhera Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00905268
• Collaborator: (none)
• Enrollment: 232
• Locations: 13
• Arms: 4
• Duration (Months): 45
• Patients Per Site: 17.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this trial is to study the efficacy, safety and tolerability of idebenone in 12 months of treatment in children and adults with Friedreich's Ataxia. This is a randomised placebo-controlled double-blind trial conducted in Europe. Efficacy outcomes include measures of neurological impairment and function, and measures of the heart.

Condition or Disease	Intervention/Treatment	Phase
Friedreich's Ataxia	Drug: idebenone; Drug: Placebo	Phase 3

Detailed Description

Idebenone, a short-chain analogue of Co-enzyme Q10 (CoQ10), has the potential to moderate underlying causes of Friedreich's Ataxia through its antioxidant activity and its role as an electron carrier in the respiratory chain promoting mitochondrial ATP production.

The current 12-month placebo-controlled treatment study in 232 patients aims to confirm the positive effect of idebenone on neurological function, as for instance observed in the recent 48-patient, 6-month NICOSIA study in children, using the International Cooperative Ataxia Rating Scale (ICARS) and the newly developed Friedreich's Ataxia Rating Scale (FARS).

In addition, the study aims to confirm the positive effect on cardiomyopathy associated with FRDA observed in several small studies. Cardiac anatomy and function will be assessed using echocardiography, tissue Doppler imaging and cardiac MRI methods in patients with FRDA cardiomyopathy. In addition exercise capacity, measured as peak workload, will be assessed in patients able to comply with a modified exercise protocol.

Study Design

• Study Type: Interventional
• Actual Enrollment: 232 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Double-blind, Randomised, Placebo-controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A: Idebenone Patients under/equal 45 kg: idebenone 180 mg/day Patients over 45 kg: idebenone 360 mg/day	Drug: idebenone; 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Experimental: Group B: Idebenone Patients under/equal 45 kg: idebenone 450 mg/day Patients over 45 kg: idebenone 900 mg/day	Drug: idebenone; 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Experimental: C: Idebenone Patients under/equal 45 kg: idebenone 1350 mg/day Patients over 45 kg: idebenone 2250 mg/day	Drug: idebenone; 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Placebo Comparator: D: Placebo placebo	Drug: Placebo; 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.

Outcome Measures

Primary Outcome Measures

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

   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.

Secondary Outcome Measures

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

   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.

2. Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin [week 52]

   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.

3. 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 [1 year]

   (In the statistical analysis sub-population presenting with cardiac involvement as defined by the FRDA cardiomyopathy criteria)

4. Change in Peak Systolic Strain Rate From Baseline to Week 52 [1 year]

   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.

5. Change in Peak Workload From Baseline to Week 52 [1 year]

   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])).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documented diagnosis of FRDA with confirmed FRDA mutations

• Patients 8 years of age or older at baseline

• Patients with body weight ≥ 25kg

• Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the medication

• Negative urine pregnancy test at screening and at baseline (women of childbearing potential)

Exclusion Criteria:

• Treatment with idebenone or Coenzyme Q10 within the past 1 month

• Pregnancy and/or breast-feeding

• Clinically significant abnormalities of clinical haematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of SGOT, SGPT, or creatinine

• Past or present history of abuse of drugs or alcohol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universitätsklinik Innsbruck	Innsbruck		Austria	6020
2	Hôpital Erasme - Université Libre de Bruxelles	Bruxelles		Belgium	1070
3	Hôpital de la Salpêtrière - INSERM U679, Neurologie et Thérapeutique expérimentale	Paris		France	75651
4	HELIOS Klinikum BerlinBuch	Berlin		Germany	13125
5	Neurologische Universitätsklinik und Poliklinik- Universitätsklinikum Bonn	Bonn		Germany	53105
6	Klinik II, Neuropädiatrie u.Muskelerkrankungen- Universitätsklinik Freiburg	Freiburg		Germany	79106
7	Zentrum für Neurologische Medizin	Göttingen		Germany	37073
8	UKE Hamburg Neuropädiatrie-Zentum für Frauen, Kinder und Jugendmedizin	Hamburg		Germany	20246
9	Neurologische Klinik- klinikum Grosshadern	München		Germany	81377
10	Neurologische Universitätsklinik und Poliklinik	Tübingen		Germany	72076
11	University Medical Center Groningen	Groningen		Netherlands	9700 RB
12	National Hospital for Neurology & Neurosurgery	London		United Kingdom	WC1N 3BG
13	University of Newcastle upon Tyne -Mitochondrial Research Group	Newcastle		United Kingdom	NE2 4HH

Sponsors and Collaborators

• Santhera Pharmaceuticals

Investigators

• Principal Investigator: Nick Wood, Professor, Dept of Molecular Neuroscience, Institute of Neurology. The National Hospital, University college London.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Santhera Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00905268
• Other Study ID Numbers: SNT-III-001
• First Posted: May 20, 2009
• Last Update Posted: Jun 27, 2016
• Last Verified: May 1, 2016

• Keywords provided by Santhera Pharmaceuticals: FRDA; idebenone; FRDA disease
• Additional relevant MeSH terms: Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Idebenone

Study Results

Participant Flow

Arm/Group Title	Group A: Idebenone	Group B: Idebenone	C: Idebenone	D: Placebo
Arm/Group Description	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.	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.	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.	placebo Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Period Title: Overall Study
STARTED	57	57	59	59
COMPLETED	53	56	59	57
NOT COMPLETED	4	1	0	2

Baseline Characteristics

Arm/Group Title	Group A: Idebenone	Group B: Idebenone	C: Idebenone	D: Placebo	Total
Arm/Group Description	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.	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.	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.	placebo Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.	Total of all reporting groups
Overall Participants	57	57	59	59	232
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.9 (13.7)	31.6 (13.1)	30.9 (13.6)	30.4 (13.3)	30.9 (13.3)
Sex: Female, Male (Count of Participants)
Female	23 40.4%	25 43.9%	27 45.8%	32 54.2%	107 46.1%
Male	34 59.6%	32 56.1%	32 54.2%	27 45.8%	125 53.9%
Region of Enrollment (participants) [Number]
Germany	40 70.2%	41 71.9%	39 66.1%	36 61%	156 67.2%
United Kingdom	4 7%	6 10.5%	6 10.2%	5 8.5%	21 9.1%
Austria	2 3.5%	4 7%	2 3.4%	5 8.5%	13 5.6%
Belgium	3 5.3%	1 1.8%	5 8.5%	4 6.8%	13 5.6%
France	5 8.8%	2 3.5%	4 6.8%	6 10.2%	17 7.3%
Netherlands	3 5.3%	3 5.3%	3 5.1%	3 5.1%	12 5.2%

Outcome Measures

1. Primary Outcome

Title	Absolute Change in International Cooperative Ataxia Rating Scale (ICARS) Scores From Baseline Assessment to Week 52
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Group A: Idebenone	Group B: Idebenone	C: Idebenone	D: Placebo
Arm/Group Description	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.	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.	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.	placebo Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Measure Participants	55	55	59	58
Mean (Standard Deviation) [units on a scale]	1.6 (5.85)	1.7 (6.64)	1.2 (5.22)	1.1 (6.76)

2. Secondary Outcome

Title	Absolute Change in Friedreich's Ataxia Rating Scale (FARS) Scores From Baseline Assessment to Week 52
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

Outcome Measure Data

Analysis Population Description

The comparison was carried out in the ITT population, on data imputed using the last observation carried forward (LOCF) method.

Arm/Group Title	Group A: Idebenone	Group B: Idebenone	C: Idebenone	D: Placebo
Arm/Group Description	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.	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.	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.	placebo Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Measure Participants	54	54	59	58
Mean (Standard Deviation) [units on a scale]	0.9 (7.19)	1.2 (5.24)	1.4 (5.60)	0.9 (6.77)

3. Secondary Outcome

Title	Proportion of Patients Improving (Responding) on ICARS by a Clinically Relevant Margin
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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Group A: Idebenone	Group B: Idebenone	C: Idebenone	D: Placebo
Arm/Group Description	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.	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.	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.	placebo Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Measure Participants	55	55	59	58
Number [percentage of patients]	18.2	23.6	23.7	31

4. Secondary Outcome

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
Description	(In the statistical analysis sub-population presenting with cardiac involvement as defined by the FRDA cardiomyopathy criteria)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Subgroup of subjects with cardiac involvement as defined by Friedreich's ataxia cardiomyopathy (FRDA-CM)

Arm/Group Title	Group A: Idebenone	Group B: Idebenone	C: Idebenone	D: Placebo
Arm/Group Description	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.	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.	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.	placebo Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Measure Participants	36	35	33	34
Number [percentage of patients]	50	51.4	30.3	44.1

5. Secondary Outcome

Title	Change in Peak Systolic Strain Rate From Baseline to Week 52
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

Outcome Measure Data

Analysis Population Description

Subgroup of subjects with cardiac involvement as defined by Friedreich's ataxia cardiomyopathy (FRDA-CM)

Arm/Group Title	Group A: Idebenone	Group B: Idebenone	C: Idebenone	D: Placebo
Arm/Group Description	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.	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.	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.	placebo Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Measure Participants	36	35	33	34
Mean (Standard Deviation) [1/s]	0.007 (0.220)	-0.004 (0.265)	0.085 (0.227)	0.024 (0.192)

6. Secondary Outcome

Title	Change in Peak Workload From Baseline to Week 52
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A: Idebenone	Group B: Idebenone	C: Idebenone	D: Placebo
Arm/Group Description	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.	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.	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.	placebo Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
Measure Participants	55	55	59	58
Mean (Standard Deviation) [Watts]	1.15 (16.362)	-7.41 (34.499)	-6.91 (20.179)	-1.54 (16.509)

Adverse Events

Arm/Group Title	Group A: Idebenone		Group B: Idebenone		C: Idebenone		D: Placebo
Arm/Group Description	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.		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.		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.		placebo Placebo: 12 months of 1 of 3 treatments arms of oral idebenone or placebo.Treatment taken 3 times daily with meals.
All Cause Mortality
	Group A: Idebenone		Group B: Idebenone		C: Idebenone		D: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group A: Idebenone		Group B: Idebenone		C: Idebenone		D: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/57 (12.3%)		4/57 (7%)		8/59 (13.6%)		7/59 (11.9%)
Cardiac disorders
hypertrophic cardiomyopathy	0/57 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	1/59 (1.7%)	1
supraventricular tachycardia	1/57 (1.8%)	1	0/57 (0%)	0	0/59 (0%)	0	2/59 (3.4%)	2
Atrial fibrillation	1/57 (1.8%)	1	1/57 (1.8%)	1	1/59 (1.7%)	1	1/59 (1.7%)	1
tachycardia	1/57 (1.8%)	1	0/57 (0%)	0	0/59 (0%)	0	0/59 (0%)	0
atrial flutter	1/57 (1.8%)	1	0/57 (0%)	0	0/59 (0%)	0	0/59 (0%)	0
suparventricular extrasystoles	1/57 (1.8%)	1	0/57 (0%)	0	0/59 (0%)	0	0/59 (0%)	0
cardiac failure	0/57 (0%)	0	1/57 (1.8%)	1	0/59 (0%)	0	0/59 (0%)	0
Endocrine disorders
diabetes mellitus	0/57 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	1/59 (1.7%)	1
Gastrointestinal disorders
Gastritis	0/57 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	1/59 (1.7%)	1
inguinal hernia	2/57 (3.5%)	2	0/57 (0%)	0	0/59 (0%)	0	0/59 (0%)	0
diarrhea	0/57 (0%)	0	1/57 (1.8%)	1	0/59 (0%)	0	0/59 (0%)	0
gastrointestinal infection	0/57 (0%)	0	1/57 (1.8%)	1	0/59 (0%)	0	0/59 (0%)	0
General disorders
influenza like illness	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/59 (0%)	0
procedural pain	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/59 (0%)	0
Infections and infestations
Sinusitis	0/57 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	1/59 (1.7%)	1
gastroenteritis	0/57 (0%)	0	0/57 (0%)	0	0/59 (0%)	0	1/59 (1.7%)	1
staphylococcal sepsis	0/57 (0%)	0	1/57 (1.8%)	1	0/59 (0%)	0	0/59 (0%)	0
urinary tract infection	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/59 (0%)	0
Injury, poisoning and procedural complications
hand fracture	0/57 (0%)	0	1/57 (1.8%)	1	0/59 (0%)	0	0/59 (0%)	0
spinal fracture	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/59 (0%)	0
Investigations
blood creatinine abnormal	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/59 (0%)	0
Musculoskeletal and connective tissue disorders
osteoarthritis	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/59 (0%)	0
Pregnancy, puerperium and perinatal conditions
abortion spontaneous	1/57 (1.8%)	1	0/57 (0%)	0	0/59 (0%)	0	0/59 (0%)	0
drug exposure during pregnancy	1/57 (1.8%)	1	0/57 (0%)	0	0/59 (0%)	0	0/59 (0%)	0
Psychiatric disorders
depression	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/59 (0%)	0
suicide attempt	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/59 (0%)	0
Renal and urinary disorders
renal tubular necrosis	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	0/59 (0%)	0
Respiratory, thoracic and mediastinal disorders
bronchitis	0/57 (0%)	0	1/57 (1.8%)	1	0/59 (0%)	0	0/59 (0%)	0
pneumonia aspiration	0/57 (0%)	0	1/57 (1.8%)	1	0/59 (0%)	0	0/59 (0%)	0
chest pain	0/57 (0%)	0	1/57 (1.8%)	1	0/59 (0%)	0	0/59 (0%)	0
Other (Not Including Serious) Adverse Events
	Group A: Idebenone		Group B: Idebenone		C: Idebenone		D: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/57 (96.5%)		52/57 (91.2%)		52/59 (88.1%)		55/59 (93.2%)
Cardiac disorders
palpitations	1/57 (1.8%)	1	1/57 (1.8%)	1	3/59 (5.1%)	3	2/59 (3.4%)	2
tachycardia	3/57 (5.3%)	3	0/57 (0%)	0	1/59 (1.7%)	1	2/59 (3.4%)	2
Ear and labyrinth disorders
vertigo	1/57 (1.8%)	1	2/57 (3.5%)	2	0/59 (0%)	0	3/59 (5.1%)	3
Gastrointestinal disorders
diarrhea	10/57 (17.5%)	10	16/57 (28.1%)	16	10/59 (16.9%)	10	8/59 (13.6%)	8
vomiting	9/57 (15.8%)	9	5/57 (8.8%)	5	7/59 (11.9%)	7	2/59 (3.4%)	2
abdominal pain upper	3/57 (5.3%)	3	6/57 (10.5%)	6	6/59 (10.2%)	6	6/59 (10.2%)	6
abdominal pain	4/57 (7%)	4	5/57 (8.8%)	5	2/59 (3.4%)	2	7/59 (11.9%)	7
toothache	1/57 (1.8%)	1	6/57 (10.5%)	6	4/59 (6.8%)	4	3/59 (5.1%)	3
dyspepsia	0/57 (0%)	0	4/57 (7%)	4	1/59 (1.7%)	1	2/59 (3.4%)	2
flatulence	0/57 (0%)	0	0/57 (0%)	0	1/59 (1.7%)	1	3/59 (5.1%)	3
General disorders
fatigue	5/57 (8.8%)	5	2/57 (3.5%)	2	2/59 (3.4%)	2	5/59 (8.5%)	5
edema peripheral	0/57 (0%)	0	3/57 (5.3%)	3	3/59 (5.1%)	3	1/59 (1.7%)	1
pyrexia	1/57 (1.8%)	1	3/57 (5.3%)	3	0/59 (0%)	0	3/59 (5.1%)	3
influenza like illness	1/57 (1.8%)	1	0/57 (0%)	0	3/59 (5.1%)	3	0/59 (0%)	0
Infections and infestations
nasopharyngitis	22/57 (38.6%)	22	25/57 (43.9%)	25	21/59 (35.6%)	21	21/59 (35.6%)	21
influenza	7/57 (12.3%)	7	6/57 (10.5%)	6	4/59 (6.8%)	4	5/59 (8.5%)	5
bronchitis	3/57 (5.3%)	3	3/57 (5.3%)	3	4/59 (6.8%)	4	1/59 (1.7%)	1
sinusitis	2/57 (3.5%)	2	1/57 (1.8%)	1	3/59 (5.1%)	3	4/59 (6.8%)	4
gastroenteritis	1/57 (1.8%)	1	2/57 (3.5%)	2	3/59 (5.1%)	3	2/59 (3.4%)	2
upper respiratory tract infection	2/57 (3.5%)	2	1/57 (1.8%)	1	3/59 (5.1%)	3	2/59 (3.4%)	2
cystitis	1/57 (1.8%)	1	4/57 (7%)	4	1/59 (1.7%)	1	1/59 (1.7%)	1
rhinitis	2/57 (3.5%)	2	0/57 (0%)	0	1/59 (1.7%)	1	3/59 (5.1%)	3
Injury, poisoning and procedural complications
fall	4/57 (7%)	4	7/57 (12.3%)	7	2/59 (3.4%)	2	7/59 (11.9%)	7
Musculoskeletal and connective tissue disorders
pain in extremity	4/57 (7%)	4	7/57 (12.3%)	7	5/59 (8.5%)	5	5/59 (8.5%)	5
muscle spasms	1/57 (1.8%)	1	2/57 (3.5%)	2	2/59 (3.4%)	2	5/59 (8.5%)	5
Nervous system disorders
headache	16/57 (28.1%)	16	20/57 (35.1%)	20	15/59 (25.4%)	15	23/59 (39%)	23
Respiratory, thoracic and mediastinal disorders
cough	11/57 (19.3%)	11	2/57 (3.5%)	2	6/59 (10.2%)	6	6/59 (10.2%)	6
oropharyngeal pain	5/57 (8.8%)	5	6/57 (10.5%)	6	6/59 (10.2%)	6	7/59 (11.9%)	7
Skin and subcutaneous tissue disorders
rash	3/57 (5.3%)	3	1/57 (1.8%)	1	1/59 (1.7%)	1	3/59 (5.1%)	3

Limitations/Caveats

[Not Specified]

More Information

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.