Friedreich's Ataxia
Conditions
Keywords
Friedreich's Ataxia, Idebenone, ICARS
Brief summary
This study is meant to assess the safety and tolerability of idebenone in patients with Friedreich's Ataxia over a 12 months period.
Detailed description
The study involves 6 clinic visits.
Interventions
DRUGIdebenone
Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day; Patients \> 45 kg/99 lbs: idebenone 2250 mg/day
Sponsors
Santhera Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Friedreich's ataxia patients completing core study SNT-III-002 (NCT00537680) and presenting at Week 24 (Visit 5) of that study * Body weight ≥ 25kg/55 lbs * Negative urine pregnancy test * Patients who in the opinion of the investigator are able to comply with the requirements of this study
Exclusion criteria
* Adverse events during the course of SNT-III-002(NCT00537680)which in the opinion of the investigator are attributable to idebenone and preclude further treatment with idebenone * Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 2 times the upper limit of normal of AST, ALT or creatinine * Treatment with coenzyme Q10, vitamin E (if taken at a dose 5 times above the daily requirement) or other sources of idebenone within the past month * Parallel participation in another clinical drug trial * Past or present history of abuse of drugs or alcohol * Pregnancy or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ICARS | baseline and 12 months | International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. A total score of 0 points represents the best possible score, and a value of 100 points is the worst possible score. Therefore, a negative change in ICARS score represents an improvement. A higher score also indicates more disability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FARS (Friedreich's Ataxia Rating Scale) | baseline and 12 Months | FARS consists of a 25 manoeuvre exam along with 4 quantitative performance measures. The neurological exam covers bulbar function, upper limb coordination, lower limb coordination, peripheral nervous system function, deep tendon reflexes, stability and gait. The use of FARS has been recently validated as a sensitive scale for this population. The FARS consists of three subscales, comprising a general score for ataxia, a score for activities of daily living (ADL) and a neurological examination. The scores can be added to make a total score ranging from 0 to 159. A higher score indicates a greater level of disability. |
| Nature of Adverse Events | 12 Months | — |
| Frequency/Number of Mild, Moderate, and Severe Adverse Events | 12 months | — |
Countries
United States
Participant flow
Recruitment details
A total of 59 subjects completed the study. Nine subjects did not complete the study. However, neurological efficacy data (ICARS, FARS) are available for Week 52 from 61 patients. All 68 subjects enrolled in this study were included in the Safety population.
Participants by arm
| Arm | Count |
|---|---|
| High Dose Idebenone Patients ≤ 45 kg/99 lbs: idebenone 1350 mg/day (3 x 150 mg tablets, t.i.d.)
Patients \> 45 kg/99 lbs: idebenone 2250 mg/day (5 x 150 mg tablets, t.i.d.) | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | non compliance and other | 6 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | High Dose Idebenone |
|---|---|
| Age, Categorical <=18 years | 68 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 14.0 years STANDARD_DEVIATION 2.72 |
| Region of Enrollment United States | 68 participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 66 / 68 |
| serious Total, serious adverse events | 4 / 68 |
Outcome results
Primary
Change in ICARS
International Cooperative Ataxia Rating Scale (ICARS): ICARS consists of a one-hundred-point semi-quantitative scale based upon 19 simple testing manoeuvres compartmentalized into postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders and has been previously used in this patient population with good inter-rater reliability. A total score of 0 points represents the best possible score, and a value of 100 points is the worst possible score. Therefore, a negative change in ICARS score represents an improvement. A higher score also indicates more disability.
Time frame: baseline and 12 months
Population: A total of 59 subjects completed the study. Nine subjects did not complete the study. However, neurological efficacy data (ICARS, FARS) are available for Week 52 from 61 patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose Idebenone | Change in ICARS | 1.1 units on a scale | Standard Deviation 5.64 |
Secondary
FARS (Friedreich's Ataxia Rating Scale)
FARS consists of a 25 manoeuvre exam along with 4 quantitative performance measures. The neurological exam covers bulbar function, upper limb coordination, lower limb coordination, peripheral nervous system function, deep tendon reflexes, stability and gait. The use of FARS has been recently validated as a sensitive scale for this population. The FARS consists of three subscales, comprising a general score for ataxia, a score for activities of daily living (ADL) and a neurological examination. The scores can be added to make a total score ranging from 0 to 159. A higher score indicates a greater level of disability.
Time frame: baseline and 12 Months
Population: A total of 59 subjects completed the study. Nine subjects did not complete the study. However, neurological efficacy data (ICARS, FARS) are available for Week 52 from 61 patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose Idebenone | FARS (Friedreich's Ataxia Rating Scale) | 2.3 units on a scale | Standard Deviation 5.59 |
Secondary
Frequency/Number of Mild, Moderate, and Severe Adverse Events
Time frame: 12 months
Population: All 68 subjects enrolled in this study were included in the Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose Idebenone | Frequency/Number of Mild, Moderate, and Severe Adverse Events | mild | 30 events |
| High Dose Idebenone | Frequency/Number of Mild, Moderate, and Severe Adverse Events | moderate | 32 events |
| High Dose Idebenone | Frequency/Number of Mild, Moderate, and Severe Adverse Events | severe | 4 events |
Secondary
Nature of Adverse Events
Time frame: 12 Months
Population: All 68 subjects enrolled in this study were included in the Safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose Idebenone | Nature of Adverse Events | Infections and Infestations | 117 events |
| High Dose Idebenone | Nature of Adverse Events | Gastrointestinal Disorders | 97 events |
| High Dose Idebenone | Nature of Adverse Events | Musculoskeletal and Connective Tissue Disorders | 75 events |