Freidreich's Ataxia
Conditions
Keywords
FRDA, idebenone, FRDA disease
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.
Interventions
DRUGidebenone
Idebenone 1350 mg/d, patients \< or equal 45 kg Idebenone 2250 mg/d, patients \> 45 kg
Sponsors
Santhera Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Austria, Belgium, France, Germany, Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 200 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 14 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 36 |
Baseline characteristics
| Characteristic | Idebenone |
|---|---|
| Age, Continuous | 32 years STANDARD_DEVIATION 13.68 |
| Region of Enrollment Austria | 6 participants |
| Region of Enrollment Belgium | 10 participants |
| Region of Enrollment France | 13 participants |
| Region of Enrollment Germany | 143 participants |
| Region of Enrollment Netherlands | 8 participants |
| Region of Enrollment United Kingdom | 20 participants |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 188 / 200 |
| serious Total, serious adverse events | 49 / 200 |
Outcome results
Primary
Absolute Change in The International Cooperative Ataxia Rating Scale (ICARS)
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
Population: Changes in Total ICARS Score for all patients completing the study (CC Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idebenone | 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 |
| Idebenone | 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 |
Primary
Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs)
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Idebenone | Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs) | With at least one AE | 188 participants |
| Idebenone | Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs) | With at least one drug-related AE | 109 participants |
| Idebenone | Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs) | With at least one severe AE | 8 participants |
| Idebenone | Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs) | With any significant AE | 54 participants |
| Idebenone | Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs) | Death | 1 participants |
| Idebenone | Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs) | Other serious adverse events than death | 48 participants |
| Idebenone | Measures of Safety and Tolerability: Nature and Frequency of Adverse Events (AEs) | AEs leading to discontinuation | 26 participants |
Other Pre-specified
Measures of Safety and Tolerability: Electrocardiograms (ECGs)
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
Other Pre-specified
Measures of Safety and Tolerability: Haematological and Biochemical Laboratory Parameters
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
Other Pre-specified
Measures of Safety and Tolerability: Physical Examinations and Vital Signs
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