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

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ClinicalTrials.gov Identifier: NCT00993967
Recruitment Status : Completed
First Posted : October 14, 2009
Results First Posted : March 5, 2018
Last Update Posted : March 5, 2018
Sponsor:
Information provided by (Responsible Party):
Santhera Pharmaceuticals

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Freidreich's Ataxia
Intervention Drug: idebenone
Enrollment 200
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Idebenone
Hide 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
Reason Not Completed
Adverse Event             8
Death             1
Lost to Follow-up             14
Withdrawal by Subject             36
Protocol Violation             2
Arm/Group Title Idebenone
Hide 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 Number of Baseline Participants 200
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 200 participants
32  (13.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 200 participants
Female
93
  46.5%
Male
107
  53.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 200 participants
Netherlands 8
Austria 6
Belgium 10
France 13
Germany 143
United Kingdom 20
1.Primary Outcome
Title Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Idebenone
Hide 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 Number of Participants Analyzed 200
Measure Type: Number
Unit of Measure: participants
With at least one AE 188
With at least one drug-related AE 109
With at least one severe AE 8
With any significant AE 54
Death 1
Other serious adverse events than death 48
AEs leading to discontinuation 26
2.Primary Outcome
Title Absolute Change in The International Cooperative Ataxia Rating Scale (ICARS)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Changes in Total ICARS Score for all patients completing the study (CC Population)
Arm/Group Title Idebenone
Hide 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 Number of Participants Analyzed 139
Mean (Standard Deviation)
Unit of Measure: units on a scale
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
Hide 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 Not Reported
4.Other Pre-specified Outcome
Title Measures of Safety and Tolerability: Electrocardiograms (ECGs)
Hide 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 Not Reported
5.Other Pre-specified Outcome
Title Measures of Safety and Tolerability: Haematological and Biochemical Laboratory Parameters
Hide 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 Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Idebenone
Hide 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 (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Idebenone
Affected / at Risk (%) # Events
Total   49/200 (24.50%)    
Cardiac disorders   
Atrial fibrillation  3/200 (1.50%)  4
Atrial flutter  2/200 (1.00%)  2
cardiac failure  1/200 (0.50%)  1
Atrial tachycardia  1/200 (0.50%)  1
Tachycardia  2/200 (1.00%)  2
myocardial infarction  1/200 (0.50%)  1
ventricular tachycardia  1/200 (0.50%)  1
Congenital, familial and genetic disorders   
talipes  1/200 (0.50%)  2
Endocrine disorders   
thyroid cancer  1/200 (0.50%)  1
Eye disorders   
corneal erosion  1/200 (0.50%)  1
Gastrointestinal disorders   
abdominal pain lower  1/200 (0.50%)  1
diarrhoea  2/200 (1.00%)  2
dental caries  1/200 (0.50%)  1
tooth disorder  1/200 (0.50%)  1
gastroenteritis  2/200 (1.00%)  2
Reflux oesophagitis  1/200 (0.50%)  1
proctitis  1/200 (0.50%)  1
abdominal pain upper  1/200 (0.50%)  1
constipation  1/200 (0.50%)  1
Infections and infestations   
streptococcal infection  1/200 (0.50%)  1
lower respiratory tract infection  1/200 (0.50%)  1
Pneumonia  1/200 (0.50%)  1
influenza  1/200 (0.50%)  1
salmonella sepsis  1/200 (0.50%)  1
Injury, poisoning and procedural complications   
Thermal burn  2/200 (1.00%)  2
liver injury  1/200 (0.50%)  1
fall  1/200 (0.50%)  1
Metabolism and nutrition disorders   
Diabetes mellitus inadequate control  1/200 (0.50%)  1
Diabetes mellitus  1/200 (0.50%)  1
dehydration  1/200 (0.50%)  1
hypoglycemia  1/200 (0.50%)  1
Musculoskeletal and connective tissue disorders   
spinal disorder  1/200 (0.50%)  1
ankle fracture  1/200 (0.50%)  1
Humerus fracture  1/200 (0.50%)  1
Pelvic fracture  2/200 (1.00%)  2
fibula fracture  2/200 (1.00%)  2
Tibia fracture  1/200 (0.50%)  1
femur fracture  1/200 (0.50%)  1
torticollis  1/200 (0.50%)  1
scoliosis  2/200 (1.00%)  2
back pain  2/200 (1.00%)  2
hand fracture  1/200 (0.50%)  1
wrist fracture  1/200 (0.50%)  1
foot deformity  1/200 (0.50%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
fibroadenoma of breast  1/200 (0.50%)  1
Uterine leiomyoma  1/200 (0.50%)  1
Nervous system disorders   
Cerebrovascular accident  1/200 (0.50%)  1
epilepsy  1/200 (0.50%)  1
radiculopathy  1/200 (0.50%)  1
paraplegia  1/200 (0.50%)  1
Renal and urinary disorders   
calculus ureteric  1/200 (0.50%)  1
Reproductive system and breast disorders   
prostatitis  1/200 (0.50%)  1
Respiratory, thoracic and mediastinal disorders   
asthma  1/200 (0.50%)  1
respiratory failure  1/200 (0.50%)  1
pneumonia aspiration  1/200 (0.50%)  1
Vascular disorders   
deep vein thrombosis  1/200 (0.50%)  1
pulmonary embolism  1/200 (0.50%)  1
Haemorrhage  1/200 (0.50%)  1
1
Term from vocabulary, MedDRA (Unspecified)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Idebenone
Affected / at Risk (%) # Events
Total   188/200 (94.00%)    
Gastrointestinal disorders   
abdominal pain upper  16/200 (8.00%)  16
diarrhoea  37/200 (18.50%)  37
nausea  20/200 (10.00%)  20
vomiting  11/200 (5.50%)  11
General disorders   
pyrexia  10/200 (5.00%)  10
Infections and infestations   
bronchitis  12/200 (6.00%)  12
cystitis  12/200 (6.00%)  12
influenza  19/200 (9.50%)  19
nasopharyngitis  67/200 (33.50%)  67
Injury, poisoning and procedural complications   
fall  13/200 (6.50%)  13
Musculoskeletal and connective tissue disorders   
back pain  17/200 (8.50%)  17
pain in extremity  15/200 (7.50%)  15
Nervous system disorders   
dizziness  10/200 (5.00%)  10
headache  52/200 (26.00%)  52
Psychiatric disorders   
depression  10/200 (5.00%)  10
Respiratory, thoracic and mediastinal disorders   
cough  19/200 (9.50%)  19
oropharyngeal pain  13/200 (6.50%)  13
1
Term from vocabulary, MedDRA (Unspecified)
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: Thomas Meier, PhD
Organization: Santhera Pharmaceuticals
Phone: +41 61 906 89 50
Responsible Party: Santhera Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00993967     History of Changes
Other Study ID Numbers: SNT-III-001-E
First Submitted: October 13, 2009
First Posted: October 14, 2009
Results First Submitted: October 14, 2016
Results First Posted: March 5, 2018
Last Update Posted: March 5, 2018