Trial Outcomes & Findings for Long-Term Safety and Tolerability of Idebenone in Friedreich's Ataxia Patients (MICONOS Extension) (NCT NCT00993967)
NCT ID: NCT00993967
Last Updated: 2018-03-05
Results Overview
Global Overvbiew of accurance of AEs-Safety population. The Safety population included all subjects who received at least one dose of the study medication.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
200 participants
Primary outcome timeframe
overall study, up to 24 months
Results posted on
2018-03-05
Participant Flow
Participant milestones
| Measure |
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.
idebenone: Idebenone 1350 mg/d, patients \< or equal 45 kg Idebenone 2250 mg/d, patients \> 45 kg
|
|---|---|
|
Overall Study
STARTED
|
200
|
|
Overall Study
COMPLETED
|
139
|
|
Overall Study
NOT COMPLETED
|
61
|
Reasons for withdrawal
| Measure |
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.
idebenone: Idebenone 1350 mg/d, patients \< or equal 45 kg Idebenone 2250 mg/d, patients \> 45 kg
|
|---|---|
|
Overall Study
Adverse Event
|
8
|
|
Overall Study
Death
|
1
|
|
Overall Study
Lost to Follow-up
|
14
|
|
Overall Study
Withdrawal by Subject
|
36
|
|
Overall Study
Protocol Violation
|
2
|
Baseline Characteristics
Long-Term Safety and Tolerability of Idebenone in Friedreich's Ataxia Patients (MICONOS Extension)
Baseline characteristics by cohort
| Measure |
Idebenone
n=200 Participants
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
|
|---|---|
|
Age, Continuous
|
32 years
STANDARD_DEVIATION 13.68 • n=5 Participants
|
|
Sex: Female, Male
Female
|
93 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
107 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
8 participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
10 participants
n=5 Participants
|
|
Region of Enrollment
France
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
143 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: overall study, up to 24 monthsGlobal Overvbiew of accurance of AEs-Safety population. The Safety population included all subjects who received at least one dose of the study medication.
Outcome measures
| Measure |
Idebenone
n=200 Participants
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
|
|---|---|
|
Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
Death
|
1 participants
|
|
Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
Other serious adverse events than death
|
48 participants
|
|
Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
AEs leading to discontinuation
|
26 participants
|
|
Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
With at least one AE
|
188 participants
|
|
Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
With at least one drug-related AE
|
109 participants
|
|
Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
With at least one severe AE
|
8 participants
|
|
Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
With any significant AE
|
54 participants
|
PRIMARY outcome
Timeframe: Baseline, Month 12 and month 24Population: Changes in Total ICARS Score for all patients completing the study (CC Population)
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.
Outcome measures
| Measure |
Idebenone
n=139 Participants
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
|
|---|---|
|
Absolute Change in The International Cooperative Ataxia Rating Scale (ICARS)
From Baseline to Month 12
|
1.41 units on a scale
Standard Deviation 7.14
|
|
Absolute Change in The International Cooperative Ataxia Rating Scale (ICARS)
From Baseline to Month 24
|
2.88 units on a scale
Standard Deviation 7.57
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Month 1, 3, 6, 12, 18 and 24Assessment of the head, eyes, ears, nose, throat, heart, chest, lungs, abdomen, extremities, peripheral pulses, skin and any other physical conditions of note.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Month 1, 3, 6, 12, 18 and 2412-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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Month 1, 3, 6, 12, 18 and 24Safety 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.
Outcome measures
Outcome data not reported
Adverse Events
Idebenone
Serious events: 49 serious events
Other events: 188 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Idebenone
n=200 participants at risk
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
|
|---|---|
|
Cardiac disorders
Atrial fibrillation
|
1.5%
3/200 • Number of events 4
|
|
Cardiac disorders
Atrial flutter
|
1.0%
2/200 • Number of events 2
|
|
Cardiac disorders
cardiac failure
|
0.50%
1/200 • Number of events 1
|
|
Congenital, familial and genetic disorders
talipes
|
0.50%
1/200 • Number of events 2
|
|
Gastrointestinal disorders
abdominal pain lower
|
0.50%
1/200 • Number of events 1
|
|
Gastrointestinal disorders
diarrhoea
|
1.0%
2/200 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
asthma
|
0.50%
1/200 • Number of events 1
|
|
Infections and infestations
streptococcal infection
|
0.50%
1/200 • Number of events 1
|
|
Gastrointestinal disorders
dental caries
|
0.50%
1/200 • Number of events 1
|
|
Gastrointestinal disorders
tooth disorder
|
0.50%
1/200 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
fibroadenoma of breast
|
0.50%
1/200 • Number of events 1
|
|
Gastrointestinal disorders
gastroenteritis
|
1.0%
2/200 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
spinal disorder
|
0.50%
1/200 • Number of events 1
|
|
Vascular disorders
deep vein thrombosis
|
0.50%
1/200 • Number of events 1
|
|
Vascular disorders
pulmonary embolism
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
ankle fracture
|
0.50%
1/200 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular accident
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Humerus fracture
|
0.50%
1/200 • Number of events 1
|
|
Infections and infestations
lower respiratory tract infection
|
0.50%
1/200 • Number of events 1
|
|
Injury, poisoning and procedural complications
Thermal burn
|
1.0%
2/200 • Number of events 2
|
|
Cardiac disorders
Atrial tachycardia
|
0.50%
1/200 • Number of events 1
|
|
Gastrointestinal disorders
Reflux oesophagitis
|
0.50%
1/200 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.50%
1/200 • Number of events 1
|
|
Vascular disorders
Haemorrhage
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pelvic fracture
|
1.0%
2/200 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.50%
1/200 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.50%
1/200 • Number of events 1
|
|
Infections and infestations
influenza
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
fibula fracture
|
1.0%
2/200 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Tibia fracture
|
0.50%
1/200 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.50%
1/200 • Number of events 1
|
|
Gastrointestinal disorders
proctitis
|
0.50%
1/200 • Number of events 1
|
|
Cardiac disorders
Tachycardia
|
1.0%
2/200 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
femur fracture
|
0.50%
1/200 • Number of events 1
|
|
Cardiac disorders
myocardial infarction
|
0.50%
1/200 • Number of events 1
|
|
Gastrointestinal disorders
abdominal pain upper
|
0.50%
1/200 • Number of events 1
|
|
Renal and urinary disorders
calculus ureteric
|
0.50%
1/200 • Number of events 1
|
|
Metabolism and nutrition disorders
dehydration
|
0.50%
1/200 • Number of events 1
|
|
Nervous system disorders
epilepsy
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
torticollis
|
0.50%
1/200 • Number of events 1
|
|
Infections and infestations
salmonella sepsis
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
scoliosis
|
1.0%
2/200 • Number of events 2
|
|
Reproductive system and breast disorders
prostatitis
|
0.50%
1/200 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
respiratory failure
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
back pain
|
1.0%
2/200 • Number of events 2
|
|
Nervous system disorders
radiculopathy
|
0.50%
1/200 • Number of events 1
|
|
Endocrine disorders
thyroid cancer
|
0.50%
1/200 • Number of events 1
|
|
Nervous system disorders
paraplegia
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
hand fracture
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
wrist fracture
|
0.50%
1/200 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
foot deformity
|
0.50%
1/200 • Number of events 1
|
|
Eye disorders
corneal erosion
|
0.50%
1/200 • Number of events 1
|
|
Cardiac disorders
ventricular tachycardia
|
0.50%
1/200 • Number of events 1
|
|
Metabolism and nutrition disorders
hypoglycemia
|
0.50%
1/200 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
pneumonia aspiration
|
0.50%
1/200 • Number of events 1
|
|
Injury, poisoning and procedural complications
liver injury
|
0.50%
1/200 • Number of events 1
|
|
Injury, poisoning and procedural complications
fall
|
0.50%
1/200 • Number of events 1
|
|
Gastrointestinal disorders
constipation
|
0.50%
1/200 • Number of events 1
|
Other adverse events
| Measure |
Idebenone
n=200 participants at risk
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
|
|---|---|
|
Gastrointestinal disorders
abdominal pain upper
|
8.0%
16/200 • Number of events 16
|
|
Gastrointestinal disorders
diarrhoea
|
18.5%
37/200 • Number of events 37
|
|
Gastrointestinal disorders
nausea
|
10.0%
20/200 • Number of events 20
|
|
Gastrointestinal disorders
vomiting
|
5.5%
11/200 • Number of events 11
|
|
General disorders
pyrexia
|
5.0%
10/200 • Number of events 10
|
|
Infections and infestations
bronchitis
|
6.0%
12/200 • Number of events 12
|
|
Infections and infestations
cystitis
|
6.0%
12/200 • Number of events 12
|
|
Infections and infestations
influenza
|
9.5%
19/200 • Number of events 19
|
|
Infections and infestations
nasopharyngitis
|
33.5%
67/200 • Number of events 67
|
|
Injury, poisoning and procedural complications
fall
|
6.5%
13/200 • Number of events 13
|
|
Musculoskeletal and connective tissue disorders
back pain
|
8.5%
17/200 • Number of events 17
|
|
Musculoskeletal and connective tissue disorders
pain in extremity
|
7.5%
15/200 • Number of events 15
|
|
Nervous system disorders
dizziness
|
5.0%
10/200 • Number of events 10
|
|
Nervous system disorders
headache
|
26.0%
52/200 • Number of events 52
|
|
Psychiatric disorders
depression
|
5.0%
10/200 • Number of events 10
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
9.5%
19/200 • Number of events 19
|
|
Respiratory, thoracic and mediastinal disorders
oropharyngeal pain
|
6.5%
13/200 • Number of events 13
|
Additional Information
Thomas Meier, PhD
Santhera Pharmaceuticals
Phone: +41 61 906 89 50
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place