Long-Term Safety and Tolerability of Idebenone in Friedreich's Ataxia Patients (MICONOS Extension)

• Sponsor: Santhera Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00993967
• Collaborator: (none)
• Enrollment: 200
• Locations: 11
• Arm: 1
• Duration (Months): 60
• Patients Per Site: 18.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is an Extension study of the MICONOS main randomised placebo-controlled trial (NCT00905268), and open to those patients completing the main study. The scientific aim of this extension study is to monitor safety and tolerability of idebenone over two years in patients with Friedreich's Ataxia.

Condition or Disease	Intervention/Treatment	Phase
Freidreich's Ataxia	Drug: idebenone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Open-Label, Single-Group, Extension Study to Obtain Long-Term Safety and Tolerability Data of Idebenone in the Treatment of Friedreich's Ataxia Patients.
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Idebenone 1350 mg/day or 2250 mg/day for patients weighing ≤45 kg or >45 kg, respectively.In case of poor tolerability, dose reduction to 450 mg/day or 900 mg/day, respectively, were allowed.	Drug: idebenone; Idebenone 1350 mg/d, patients < or equal 45 kg Idebenone 2250 mg/d, patients > 45 kg

Outcome Measures

Primary Outcome Measures

1. Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs) [overall study, up to 24 months]

   Global Overvbiew of accurance of AEs-Safety population. The Safety population included all subjects who received at least one dose of the study medication.

2. Absolute Change in The International Cooperative Ataxia Rating Scale (ICARS) [Baseline, Month 12 and month 24]

   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.

Other Outcome Measures

1. Measures of Safety and Tolerability: Physical Examinations and Vital Signs [Month 1, 3, 6, 12, 18 and 24]

   Assessment of the head, eyes, ears, nose, throat, heart, chest, lungs, abdomen, extremities, peripheral pulses, skin and any other physical conditions of note.

2. Measures of Safety and Tolerability: Electrocardiograms (ECGs) [Month 1, 3, 6, 12, 18 and 24]

   12-lead ECG recordings were performed at every visit. Each ECG was measured using 3 complexes: PR interval in lead II or V2, QRS and QT intervals and heart rate in lead II, corrected QT intervals QTcB and QTcF.

3. Measures of Safety and Tolerability: Haematological and Biochemical Laboratory Parameters [Month 1, 3, 6, 12, 18 and 24]

   Safety haematological analysis were done at every visit. Analyses included red blood cell count, haemoglobin, haematocrit, red cell indices, white blood cell count including differential, platelet count Safety biochemistry were done at every visit. Analyses included sodium, potassium, chloride, bicarbonate, urea, creatinine, calcium, inorganic phosphate, glucose, total bilirubin, total protein, albumin, aspartate amiotransferase (AST), alanine aminotransferase (ALT), alkaline phosphotase, Gamma GT, creatine kinase (CK)^, cholesterol, triglycerides, uric acid.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completion of 52 weeks in study SNT-III-001

• Body weight ≥ 25 kg

• Negative urine pregnancy test

• Eligibility to participate in the present extension study as confirmed by investigator

Exclusion Criteria:

• Safety or tolerability issues arising during the course of SNT-III-001 which in the opinion of the investigator preclude further treatment with idebenone

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

• Parallel participation in another clinical drug trial

• Pregnancy or breast-feeding

• Abuse of drugs or alcohol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universitätsklinik Innsbruck	Innsbruck		Austria
2	Hôpital Erasme - Univeristé Libre de Bruxelles	Bruxelles		Belgium	1070
3	Hôpital de la Salpétrière - INSERM U679, Neurologie et Thérapeutique expérimentale	Paris		France	75651
4	HELIOS Klinikum Berlin	Berlin		Germany	13125
5	Neurologische Universitätsklinik und Ploklinik - Universitätsklimikum Bonn	Bonn		Germany	53105
6	Klinik II, Neuropädiatrie und Muskelerkrankungen - Universitätsklinik Freiburg	Freiburg		Germany	79106
7	Zentrum für Neurologische Medizin	Göttingen		Germany	37073
8	UKE Hamburg Neuropädiatrie - Zentrum 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

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: NCT00993967
• Other Study ID Numbers: SNT-III-001-E
• First Posted: Oct 14, 2009
• Last Update Posted: Mar 5, 2018
• Last Verified: Aug 1, 2017

• 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	Idebenone
Arm/Group Description	1350 mg/day or 2250 mg/day for patients weighing ≤45 kg or >45 kg, respectively.In case of poor tolerability, dose reduction to 450 mg/day or 900 mg/day, respectively, were allowed. idebenone: Idebenone 1350 mg/d, patients < or equal 45 kg Idebenone 2250 mg/d, patients > 45 kg
Period Title: Overall Study
STARTED	200
COMPLETED	139
NOT COMPLETED	61

Baseline Characteristics

Arm/Group Title	Idebenone
Arm/Group Description	1350 mg/day or 2250 mg/day for patients weighing ≤45 kg or >45 kg, respectively.In case of poor tolerability, dose reduction to 450 mg/day or 900 mg/day, respectively, were allowed. idebenone: Idebenone 1350 mg/d, patients < or equal 45 kg Idebenone 2250 mg/d, patients > 45 kg
Overall Participants	200
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32 (13.68)
Sex: Female, Male (Count of Participants)
Female	93 46.5%
Male	107 53.5%
Region of Enrollment (participants) [Number]
Netherlands	8 4%
Austria	6 3%
Belgium	10 5%
France	13 6.5%
Germany	143 71.5%
United Kingdom	20 10%

Outcome Measures

1. Primary Outcome

Title	Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
Description	Global Overvbiew of accurance of AEs-Safety population. The Safety population included all subjects who received at least one dose of the study medication.
Time Frame	overall study, up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Idebenone
Arm/Group Description	1350 mg/day or 2250 mg/day for patients weighing ≤45 kg or >45 kg, respectively.In case of poor tolerability, dose reduction to 450 mg/day or 900 mg/day, respectively, were allowed. idebenone: Idebenone 1350 mg/d, patients < or equal 45 kg Idebenone 2250 mg/d, patients > 45 kg
Measure Participants	200
With at least one AE	188 94%
With at least one drug-related AE	109 54.5%
With at least one severe AE	8 4%
With any significant AE	54 27%
Death	1 0.5%
Other serious adverse events than death	48 24%
AEs leading to discontinuation	26 13%

2. Primary Outcome

Title	Absolute Change in The International Cooperative Ataxia Rating Scale (ICARS)
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, Month 12 and month 24

Outcome Measure Data

Analysis Population Description

Changes in Total ICARS Score for all patients completing the study (CC Population)

Arm/Group Title	Idebenone
Arm/Group Description	1350 mg/day or 2250 mg/day for patients weighing ≤45 kg or >45 kg, respectively.In case of poor tolerability, dose reduction to 450 mg/day or 900 mg/day, respectively, were allowed. idebenone: Idebenone 1350 mg/d, patients < or equal 45 kg Idebenone 2250 mg/d, patients > 45 kg
Measure Participants	139
From Baseline to Month 12	1.41 (7.14)
From Baseline to Month 24	2.88 (7.57)

3. Other Pre-specified Outcome

Title	Measures of Safety and Tolerability: Physical Examinations and Vital Signs
Description	Assessment of the head, eyes, ears, nose, throat, heart, chest, lungs, abdomen, extremities, peripheral pulses, skin and any other physical conditions of note.
Time Frame	Month 1, 3, 6, 12, 18 and 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Measures of Safety and Tolerability: Electrocardiograms (ECGs)
Description	12-lead ECG recordings were performed at every visit. Each ECG was measured using 3 complexes: PR interval in lead II or V2, QRS and QT intervals and heart rate in lead II, corrected QT intervals QTcB and QTcF.
Time Frame	Month 1, 3, 6, 12, 18 and 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Measures of Safety and Tolerability: Haematological and Biochemical Laboratory Parameters
Description	Safety haematological analysis were done at every visit. Analyses included red blood cell count, haemoglobin, haematocrit, red cell indices, white blood cell count including differential, platelet count Safety biochemistry were done at every visit. Analyses included sodium, potassium, chloride, bicarbonate, urea, creatinine, calcium, inorganic phosphate, glucose, total bilirubin, total protein, albumin, aspartate amiotransferase (AST), alanine aminotransferase (ALT), alkaline phosphotase, Gamma GT, creatine kinase (CK)^, cholesterol, triglycerides, uric acid.
Time Frame	Month 1, 3, 6, 12, 18 and 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Idebenone
Arm/Group Description	1350 mg/day or 2250 mg/day for patients weighing ≤45 kg or >45 kg, respectively.In case of poor tolerability, dose reduction to 450 mg/day or 900 mg/day, respectively, were allowed. idebenone: Idebenone 1350 mg/d, patients < or equal 45 kg Idebenone 2250 mg/d, patients > 45 kg
All Cause Mortality
	Idebenone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Idebenone
	Affected / at Risk (%)	# Events
Total	49/200 (24.5%)
Cardiac disorders
Atrial fibrillation	3/200 (1.5%)	4
Atrial flutter	2/200 (1%)	2
cardiac failure	1/200 (0.5%)	1
Atrial tachycardia	1/200 (0.5%)	1
Tachycardia	2/200 (1%)	2
myocardial infarction	1/200 (0.5%)	1
ventricular tachycardia	1/200 (0.5%)	1
Congenital, familial and genetic disorders
talipes	1/200 (0.5%)	2
Endocrine disorders
thyroid cancer	1/200 (0.5%)	1
Eye disorders
corneal erosion	1/200 (0.5%)	1
Gastrointestinal disorders
abdominal pain lower	1/200 (0.5%)	1
diarrhoea	2/200 (1%)	2
dental caries	1/200 (0.5%)	1
tooth disorder	1/200 (0.5%)	1
gastroenteritis	2/200 (1%)	2
Reflux oesophagitis	1/200 (0.5%)	1
proctitis	1/200 (0.5%)	1
abdominal pain upper	1/200 (0.5%)	1
constipation	1/200 (0.5%)	1
Infections and infestations
streptococcal infection	1/200 (0.5%)	1
lower respiratory tract infection	1/200 (0.5%)	1
Pneumonia	1/200 (0.5%)	1
influenza	1/200 (0.5%)	1
salmonella sepsis	1/200 (0.5%)	1
Injury, poisoning and procedural complications
Thermal burn	2/200 (1%)	2
liver injury	1/200 (0.5%)	1
fall	1/200 (0.5%)	1
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/200 (0.5%)	1
Diabetes mellitus	1/200 (0.5%)	1
dehydration	1/200 (0.5%)	1
hypoglycemia	1/200 (0.5%)	1
Musculoskeletal and connective tissue disorders
spinal disorder	1/200 (0.5%)	1
ankle fracture	1/200 (0.5%)	1
Humerus fracture	1/200 (0.5%)	1
Pelvic fracture	2/200 (1%)	2
fibula fracture	2/200 (1%)	2
Tibia fracture	1/200 (0.5%)	1
femur fracture	1/200 (0.5%)	1
torticollis	1/200 (0.5%)	1
scoliosis	2/200 (1%)	2
back pain	2/200 (1%)	2
hand fracture	1/200 (0.5%)	1
wrist fracture	1/200 (0.5%)	1
foot deformity	1/200 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
fibroadenoma of breast	1/200 (0.5%)	1
Uterine leiomyoma	1/200 (0.5%)	1
Nervous system disorders
Cerebrovascular accident	1/200 (0.5%)	1
epilepsy	1/200 (0.5%)	1
radiculopathy	1/200 (0.5%)	1
paraplegia	1/200 (0.5%)	1
Renal and urinary disorders
calculus ureteric	1/200 (0.5%)	1
Reproductive system and breast disorders
prostatitis	1/200 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
asthma	1/200 (0.5%)	1
respiratory failure	1/200 (0.5%)	1
pneumonia aspiration	1/200 (0.5%)	1
Vascular disorders
deep vein thrombosis	1/200 (0.5%)	1
pulmonary embolism	1/200 (0.5%)	1
Haemorrhage	1/200 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Idebenone
	Affected / at Risk (%)	# Events
Total	188/200 (94%)
Gastrointestinal disorders
abdominal pain upper	16/200 (8%)	16
diarrhoea	37/200 (18.5%)	37
nausea	20/200 (10%)	20
vomiting	11/200 (5.5%)	11
General disorders
pyrexia	10/200 (5%)	10
Infections and infestations
bronchitis	12/200 (6%)	12
cystitis	12/200 (6%)	12
influenza	19/200 (9.5%)	19
nasopharyngitis	67/200 (33.5%)	67
Injury, poisoning and procedural complications
fall	13/200 (6.5%)	13
Musculoskeletal and connective tissue disorders
back pain	17/200 (8.5%)	17
pain in extremity	15/200 (7.5%)	15
Nervous system disorders
dizziness	10/200 (5%)	10
headache	52/200 (26%)	52
Psychiatric disorders
depression	10/200 (5%)	10
Respiratory, thoracic and mediastinal disorders
cough	19/200 (9.5%)	19
oropharyngeal pain	13/200 (6.5%)	13

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.