Friedreich Ataxia
Conditions
Brief summary
The purpose of this protocol is to determine the efficacy of EGb 761 120 mg bid versus placebo in patients suffering from Friedreich Ataxia
Interventions
DRUGEGb 761 120 mg
EGb 761® 120 mg bid, orally for 12 to 14 weeks
DRUGPlacebo
Placebo 1 tablet BID, orally for 12 to 14 weeks
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 22 Years
Healthy volunteers
No
Inclusion criteria
* Friedreich ataxia diagnosis confirmed by evidenced mutation expansion of Frataxin gene * Ambulatory patient, with depressed tendon reflexes and pyramidal syndrome associated or not to a loss of position or vibration senses or dysarthria * Patient able to perform the tests of the study
Exclusion criteria
* Severe cardiac disease as assessed by echocardiography performed at least within 6 months before screening or during the wash out period (4 weeks) * Absolute contra-indication to Nuclear Magnetic Resonance spectroscopy(NMR) examination: iron and any magnetic objects implanted in the whole body, e.g. some neurostimulators, cardiac pace-makers, vascular clips and other implanted orthopaedic prosthesis * Patient who did not deplete at baseline phosphocreatine (PCr) pool by more than 30 % during the exercise bout * Any continuous use of the following forbidden medications: * other antioxidant such as idebenone, coenzyme Q, vitamin E/C taken for less than 4 weeks prior study treatment start (ie for antioxidant drugs a mandatory wash-out period of 4 weeks prior study drug start has to be observed), * any other vasodilators * tranquilizer such as benzodiazepine, meprobamate or buspirone, and/or antidepressant (only one), at non stable dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Creatine Rephosphorylation Rate Post Exercise | Baseline (Week 0) to Week 12 | Creatine Rephosphorylation Rate post exercise measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy and calculated with correction according to muscular pH. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Peak Perfusion | Baseline (Week 0) to Week 12 | — |
| Perfusion-time Integral During the First 9 Minutes Post Exercise. | Baseline (Week 0) to Week 12 | The integral of 'peak perfusion' over a period of 9 minutes post exercise. |
| Muscle Reoxygenation Rate Post Exercise. | Baseline (Week 0) to Week 12 | Muscle reoxygenation rate post exercise was assessed using Myoglobin Hydrogen-1 Nuclear Magnetic Resonance spectroscopy. |
| Muscle Trophicity: Maximum Cross Section of Muscle | Baseline (Week 0) to Week 12 | Muscle trophicity measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy and calculated based on maximum cross section of muscle (cm\^2) |
| Developed Force During the Exercise Bout | Baseline (Week 0) to Week 12 | Developed force during the exercise bout measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy |
| Normalised Work Developed During the Exercise | Baseline (Week 0) to Week 12 | Normalised work developed during the exercise was derived as Work developed during the exercise/(\[60 X Maximum cross section of muscle\]-1100). Normalised work measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy. |
| Metabolism Efficacy Index | Baseline (Week 0) to Week 12 | The metabolism efficacy index was derived as Normalised work x creatine phosphorylation rate (sec-1). \[Normalised work was derived as Work developed during the exercise/(60 X Maximum cross section of muscle-1100)\]. Greater values of Metabolism Efficacy index indicate improvement in skeletal muscle energetics while lower values indicate the reverse. Negative values obtained using the formula indicated severe levels of muscle weakness. |
| International Cooperative Ataxia Rating Scale [ICARS] (Total Score) | Baseline (Week 0) to Week 12 | The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales (i.e. Posture and gait disturbances, Kinetic functions, Speech disorders, & Oculomotor disorders). Scores for each subscale quantify the extent of ataxia in each clinically important area and subscale scores are also summed to give a total score ranging from 0 to 100, with 100 indicative of the most severely affected outcome. |
| ICARS (Posture and Gait Disturbance Score) | Baseline (Week 0) to Week 12 | The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Posture and gait disturbances. Posture and gait disturbances score range from 0 to 34 (Higher scores indicate higher levels of impairment). |
| ICARS (Kinetic Function Score) | Baseline (Week 0) to Week 12 | The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Kinetic Function. Kinetic Function score range from 0 to 52 (Higher scores indicate higher levels of impairment). |
| Peak Post Exercise Perfusion | Baseline (Week 0) to Week 12 | Peak post exercise perfusion (mL/mn/100 g of tissue) was assessed using Arterial spin labelling combined with Nuclear Magnetic Resonance imaging. |
| ICARS (Oculomotor Disorders Score) | Baseline (Week 0) to Week 12 | The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Oculomotor Disorders. Oculomotor Disorders score range from 0 to 6 (Higher scores indicate higher levels of impairment). |
| Timed 25-foot Walk Test | Baseline (Week 0) to Week 12 | — |
| Nine Hole Peg Test (Dominant Hand) | Baseline (Week 0) to Week 12 | The nine hole peg test was used to assess cognitive function and in particular, fine motor coordination. The patient was asked to place nine pegs in nine holes and was scored on the amount of time it took to place and remove all nine pegs. |
| Nine Hole Peg Test (Nondominant Hand) | Baseline (Week 0) to Week 12 | The nine hole peg test was used to assess cognitive function and in particular, fine motor coordination. The patient was asked to place nine pegs in nine holes and was scored on the amount of time it took to place and remove all nine pegs. |
| Choice Reaction Time Test- Reaction Time | Baseline (Week 0) to Week 12 | The choice reaction time test was used to assess cognitive functioning. On random presentation of one of six signal lights, the patient was asked to respond as quickly and accurately as possible by removing their index finger of the dominant hand from the bottom key and pressing whichever of the top six keys was indicated by the signal. Reaction time was the time elapsed between the presentation of the stimulus and the release of the finger and movement time was defined as the time elapsed between release of the finger and pressure of the second key. |
| Choice Reaction Time Test- Movement Time | Baseline (Week 0) to Week 12 | The choice reaction time test was used to assess cognitive functioning. On random presentation of one of six signal lights, the patient was asked to respond as quickly and accurately as possible by removing their index finger of the dominant hand from the bottom key and pressing whichever of the top six keys was indicated by the signal. Reaction time was the time elapsed between the presentation of the stimulus and the release of the finger and movement time was defined as the time elapsed between release of the finger and pressure of the second key. |
| Visual Assessment Scale (VAS) of Global Impression - Patient | Baseline (Week 0) to Week 12 | The VAS used a 10-cm scoring scale in which values were reported in mm such that 0=bad and 100=good. Total score range on VAS is from 0 to 100. |
| Visual Assessment Scale (VAS) of Global Impression - Parents | Baseline (Week 0) to Week 12 | The VAS used a 10-cm scoring scale in which values were reported in mm such that 0=bad and 100=good. Total score range on VAS is from 0 to 100. |
| Visual Assessment Scale (VAS) of Global Impression - Investigator | Baseline (Week 0) to Week 12 | The VAS used a 10-cm scoring scale in which values were reported in mm such that 0=bad and 100=good. Total score range on VAS is from 0 to 100. |
| ICARS (Speech Disorders Score) | Baseline (Week 0) to Week 12 | The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Speech Disorders. Speech Disorders Score range from 0 to 8 (Higher scores indicate higher levels of impairment). |
Countries
France
Participant flow
Recruitment details
Patients were recruited at a single centre investigational site in France.
Pre-assignment details
Overall number of baseline participants differs from number of participants who started as efficacy analysis was performed on modified Intention-To-Treat (mITT) population (i.e. 21 patients). 1 patient in the placebo group did not meet the primary criteria and thus excluded from the analysis. No patient was excluded from the safety population.
Participants by arm
| Arm | Count |
|---|---|
| EGb 761® 120 mg EGb 761 120 mg : EGb 761® 120 mg BID, orally for 12 to 14 weeks | 11 |
| Placebo Placebo : Placebo 1 tablet BID, orally for 12 to 14 weeks.
Baseline Characteristics data is based on the mITT population, which comprised of the 21 patients. One patient in the placebo group was excluded from the analyses because no assessment of the primary criteria was performed. | 10 |
| Total | 21 |
Baseline characteristics
| Characteristic | EGb 761® 120 mg | Placebo | Total |
|---|---|---|---|
| Age, Customized 12-15 years | 5 participants | 4 participants | 9 participants |
| Age, Customized 16-22 years | 6 participants | 6 participants | 12 participants |
| Duration since first symptoms | 8.1 years | 7.7 years | 7.8 years |
| Number of repeats of Guanine Adenine Adenine (GAA) sequence | 700 GAA sequence repetitions | 810 GAA sequence repetitions | 700 GAA sequence repetitions |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 11 | 7 / 11 |
| serious Total, serious adverse events | 1 / 11 | 1 / 11 |
Outcome results
Primary
Creatine Rephosphorylation Rate Post Exercise
Creatine Rephosphorylation Rate post exercise measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy and calculated with correction according to muscular pH.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Creatine Rephosphorylation Rate Post Exercise | Baseline (Week 0) | 0.024 pH per second |
| EGb 761® 120 mg | Creatine Rephosphorylation Rate Post Exercise | Week 12 | 0.022 pH per second |
| EGb 761® 120 mg | Creatine Rephosphorylation Rate Post Exercise | Change from Baseline (Week 0) to Week 12 | 0.001 pH per second |
| Placebo | Creatine Rephosphorylation Rate Post Exercise | Baseline (Week 0) | 0.029 pH per second |
| Placebo | Creatine Rephosphorylation Rate Post Exercise | Week 12 | 0.029 pH per second |
| Placebo | Creatine Rephosphorylation Rate Post Exercise | Change from Baseline (Week 0) to Week 12 | 0.000 pH per second |
p-value: 0.9133Non parametric ANCOVA on the rank test
Secondary
Choice Reaction Time Test- Movement Time
The choice reaction time test was used to assess cognitive functioning. On random presentation of one of six signal lights, the patient was asked to respond as quickly and accurately as possible by removing their index finger of the dominant hand from the bottom key and pressing whichever of the top six keys was indicated by the signal. Reaction time was the time elapsed between the presentation of the stimulus and the release of the finger and movement time was defined as the time elapsed between release of the finger and pressure of the second key.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Choice Reaction Time Test- Movement Time | Baseline (Week 0) | 561.5 millisecond |
| EGb 761® 120 mg | Choice Reaction Time Test- Movement Time | Week 12 | 555.0 millisecond |
| EGb 761® 120 mg | Choice Reaction Time Test- Movement Time | Change from Baseline (Week 0) to Week 12 | 4.5 millisecond |
| Placebo | Choice Reaction Time Test- Movement Time | Baseline (Week 0) | 531.0 millisecond |
| Placebo | Choice Reaction Time Test- Movement Time | Week 12 | 496.5 millisecond |
| Placebo | Choice Reaction Time Test- Movement Time | Change from Baseline (Week 0) to Week 12 | -31.0 millisecond |
Secondary
Choice Reaction Time Test- Reaction Time
The choice reaction time test was used to assess cognitive functioning. On random presentation of one of six signal lights, the patient was asked to respond as quickly and accurately as possible by removing their index finger of the dominant hand from the bottom key and pressing whichever of the top six keys was indicated by the signal. Reaction time was the time elapsed between the presentation of the stimulus and the release of the finger and movement time was defined as the time elapsed between release of the finger and pressure of the second key.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Choice Reaction Time Test- Reaction Time | Baseline (Week 0) | 513.5 millisecond |
| EGb 761® 120 mg | Choice Reaction Time Test- Reaction Time | Week 12 | 491.0 millisecond |
| EGb 761® 120 mg | Choice Reaction Time Test- Reaction Time | Change from Baseline (Week 0) to Week 12 | 8.5 millisecond |
| Placebo | Choice Reaction Time Test- Reaction Time | Baseline (Week 0) | 536.0 millisecond |
| Placebo | Choice Reaction Time Test- Reaction Time | Week 12 | 531.0 millisecond |
| Placebo | Choice Reaction Time Test- Reaction Time | Change from Baseline (Week 0) to Week 12 | 9.0 millisecond |
Secondary
Developed Force During the Exercise Bout
Developed force during the exercise bout measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Developed Force During the Exercise Bout | Baseline (Week 0) | 305.30 Joules |
| EGb 761® 120 mg | Developed Force During the Exercise Bout | Week 12 | 277.50 Joules |
| EGb 761® 120 mg | Developed Force During the Exercise Bout | Change from Baseline (Week 0) to Week 12 | -32.40 Joules |
| Placebo | Developed Force During the Exercise Bout | Baseline (Week 0) | 358.10 Joules |
| Placebo | Developed Force During the Exercise Bout | Week 12 | 354.35 Joules |
| Placebo | Developed Force During the Exercise Bout | Change from Baseline (Week 0) to Week 12 | 19.20 Joules |
Secondary
ICARS (Kinetic Function Score)
The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Kinetic Function. Kinetic Function score range from 0 to 52 (Higher scores indicate higher levels of impairment).
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | ICARS (Kinetic Function Score) | Baseline (Week 0) | 15.0 score on a scale |
| EGb 761® 120 mg | ICARS (Kinetic Function Score) | Week 12 | 13.0 score on a scale |
| EGb 761® 120 mg | ICARS (Kinetic Function Score) | Change from Baseline (Week 0) to Week 12 | 0.0 score on a scale |
| Placebo | ICARS (Kinetic Function Score) | Baseline (Week 0) | 11.5 score on a scale |
| Placebo | ICARS (Kinetic Function Score) | Week 12 | 13.0 score on a scale |
| Placebo | ICARS (Kinetic Function Score) | Change from Baseline (Week 0) to Week 12 | 0.5 score on a scale |
Secondary
ICARS (Oculomotor Disorders Score)
The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Oculomotor Disorders. Oculomotor Disorders score range from 0 to 6 (Higher scores indicate higher levels of impairment).
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | ICARS (Oculomotor Disorders Score) | Baseline (Week 0) | 1.0 score on a scale |
| EGb 761® 120 mg | ICARS (Oculomotor Disorders Score) | Week 12 | 2.0 score on a scale |
| EGb 761® 120 mg | ICARS (Oculomotor Disorders Score) | Change from Baseline (Week 0) to Week 12 | 0.0 score on a scale |
| Placebo | ICARS (Oculomotor Disorders Score) | Baseline (Week 0) | 1.5 score on a scale |
| Placebo | ICARS (Oculomotor Disorders Score) | Week 12 | 2.0 score on a scale |
| Placebo | ICARS (Oculomotor Disorders Score) | Change from Baseline (Week 0) to Week 12 | 0.0 score on a scale |
Secondary
ICARS (Posture and Gait Disturbance Score)
The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Posture and gait disturbances. Posture and gait disturbances score range from 0 to 34 (Higher scores indicate higher levels of impairment).
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | ICARS (Posture and Gait Disturbance Score) | Baseline (Week 0) | 19.0 score on a scale |
| EGb 761® 120 mg | ICARS (Posture and Gait Disturbance Score) | Week 12 | 18.0 score on a scale |
| EGb 761® 120 mg | ICARS (Posture and Gait Disturbance Score) | Change from Baseline (Week 0) to Week 12 | 1.0 score on a scale |
| Placebo | ICARS (Posture and Gait Disturbance Score) | Baseline (Week 0) | 12.5 score on a scale |
| Placebo | ICARS (Posture and Gait Disturbance Score) | Week 12 | 12.0 score on a scale |
| Placebo | ICARS (Posture and Gait Disturbance Score) | Change from Baseline (Week 0) to Week 12 | 2.8 score on a scale |
Secondary
ICARS (Speech Disorders Score)
The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales including Speech Disorders. Speech Disorders Score range from 0 to 8 (Higher scores indicate higher levels of impairment).
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | ICARS (Speech Disorders Score) | Baseline (Week 0) | 2.0 score on a scale |
| EGb 761® 120 mg | ICARS (Speech Disorders Score) | Week 12 | 1.0 score on a scale |
| EGb 761® 120 mg | ICARS (Speech Disorders Score) | Change from Baseline (Week 0) to Week 12 | 0.0 score on a scale |
| Placebo | ICARS (Speech Disorders Score) | Baseline (Week 0) | 0.5 score on a scale |
| Placebo | ICARS (Speech Disorders Score) | Week 12 | 1.0 score on a scale |
| Placebo | ICARS (Speech Disorders Score) | Change from Baseline (Week 0) to Week 12 | 0.0 score on a scale |
Secondary
International Cooperative Ataxia Rating Scale [ICARS] (Total Score)
The ICARS was used to measure the general clinical symptoms of Friedreich ataxia using four subscales (i.e. Posture and gait disturbances, Kinetic functions, Speech disorders, & Oculomotor disorders). Scores for each subscale quantify the extent of ataxia in each clinically important area and subscale scores are also summed to give a total score ranging from 0 to 100, with 100 indicative of the most severely affected outcome.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | International Cooperative Ataxia Rating Scale [ICARS] (Total Score) | Baseline (Week 0) | 35 score on a scale |
| EGb 761® 120 mg | International Cooperative Ataxia Rating Scale [ICARS] (Total Score) | Week 12 | 33.0 score on a scale |
| EGb 761® 120 mg | International Cooperative Ataxia Rating Scale [ICARS] (Total Score) | Change from Baseline (Week 0) to Week 12 | 0.0 score on a scale |
| Placebo | International Cooperative Ataxia Rating Scale [ICARS] (Total Score) | Baseline (Week 0) | 26.5 score on a scale |
| Placebo | International Cooperative Ataxia Rating Scale [ICARS] (Total Score) | Week 12 | 29.0 score on a scale |
| Placebo | International Cooperative Ataxia Rating Scale [ICARS] (Total Score) | Change from Baseline (Week 0) to Week 12 | 0.5 score on a scale |
Secondary
Metabolism Efficacy Index
The metabolism efficacy index was derived as Normalised work x creatine phosphorylation rate (sec-1). \[Normalised work was derived as Work developed during the exercise/(60 X Maximum cross section of muscle-1100)\]. Greater values of Metabolism Efficacy index indicate improvement in skeletal muscle energetics while lower values indicate the reverse. Negative values obtained using the formula indicated severe levels of muscle weakness.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Metabolism Efficacy Index | Baseline (Week 0) | 0.0180 per second |
| EGb 761® 120 mg | Metabolism Efficacy Index | Week 12 | 0.0130 per second |
| EGb 761® 120 mg | Metabolism Efficacy Index | Change from Baseline (Week 0) to Week 12 | 0.0010 per second |
| Placebo | Metabolism Efficacy Index | Baseline (Week 0) | 0.0150 per second |
| Placebo | Metabolism Efficacy Index | Week 12 | 0.0145 per second |
| Placebo | Metabolism Efficacy Index | Change from Baseline (Week 0) to Week 12 | -0.0010 per second |
Secondary
Muscle Reoxygenation Rate Post Exercise.
Muscle reoxygenation rate post exercise was assessed using Myoglobin Hydrogen-1 Nuclear Magnetic Resonance spectroscopy.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Muscle Reoxygenation Rate Post Exercise. | Baseline (Week 0) | 0.0870 per second |
| EGb 761® 120 mg | Muscle Reoxygenation Rate Post Exercise. | Week 12 | 0.0580 per second |
| EGb 761® 120 mg | Muscle Reoxygenation Rate Post Exercise. | Change from Baseline (Week 0) to Week 12 | -0.0350 per second |
| Placebo | Muscle Reoxygenation Rate Post Exercise. | Baseline (Week 0) | 0.0540 per second |
| Placebo | Muscle Reoxygenation Rate Post Exercise. | Week 12 | 0.0620 per second |
| Placebo | Muscle Reoxygenation Rate Post Exercise. | Change from Baseline (Week 0) to Week 12 | -0.0035 per second |
Secondary
Muscle Trophicity: Maximum Cross Section of Muscle
Muscle trophicity measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy and calculated based on maximum cross section of muscle (cm\^2)
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Muscle Trophicity: Maximum Cross Section of Muscle | Baseline (Week 0) | 28.10 cm^2 |
| EGb 761® 120 mg | Muscle Trophicity: Maximum Cross Section of Muscle | Week 12 | 26.8 cm^2 |
| EGb 761® 120 mg | Muscle Trophicity: Maximum Cross Section of Muscle | Change from Baseline (Week 0) to Week 12 | 0.10 cm^2 |
| Placebo | Muscle Trophicity: Maximum Cross Section of Muscle | Baseline (Week 0) | 28.95 cm^2 |
| Placebo | Muscle Trophicity: Maximum Cross Section of Muscle | Week 12 | 29.85 cm^2 |
| Placebo | Muscle Trophicity: Maximum Cross Section of Muscle | Change from Baseline (Week 0) to Week 12 | 0.55 cm^2 |
Secondary
Nine Hole Peg Test (Dominant Hand)
The nine hole peg test was used to assess cognitive function and in particular, fine motor coordination. The patient was asked to place nine pegs in nine holes and was scored on the amount of time it took to place and remove all nine pegs.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Nine Hole Peg Test (Dominant Hand) | Baseline (Week 0) | 38.50 seconds |
| EGb 761® 120 mg | Nine Hole Peg Test (Dominant Hand) | Week 12 | 42.00 seconds |
| EGb 761® 120 mg | Nine Hole Peg Test (Dominant Hand) | Change from Baseline (Week 0) to Week 12 | 1.50 seconds |
| Placebo | Nine Hole Peg Test (Dominant Hand) | Baseline (Week 0) | 43.50 seconds |
| Placebo | Nine Hole Peg Test (Dominant Hand) | Week 12 | 40.75 seconds |
| Placebo | Nine Hole Peg Test (Dominant Hand) | Change from Baseline (Week 0) to Week 12 | -1.50 seconds |
Secondary
Nine Hole Peg Test (Nondominant Hand)
The nine hole peg test was used to assess cognitive function and in particular, fine motor coordination. The patient was asked to place nine pegs in nine holes and was scored on the amount of time it took to place and remove all nine pegs.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Nine Hole Peg Test (Nondominant Hand) | Baseline (Week 0) | 47.50 seconds |
| EGb 761® 120 mg | Nine Hole Peg Test (Nondominant Hand) | Week 12 | 53.00 seconds |
| EGb 761® 120 mg | Nine Hole Peg Test (Nondominant Hand) | Change from Baseline (Week 0) to Week 12 | 0.50 seconds |
| Placebo | Nine Hole Peg Test (Nondominant Hand) | Change from Baseline (Week 0) to Week 12 | 1.75 seconds |
| Placebo | Nine Hole Peg Test (Nondominant Hand) | Baseline (Week 0) | 48.50 seconds |
| Placebo | Nine Hole Peg Test (Nondominant Hand) | Week 12 | 46.50 seconds |
Secondary
Normalised Work Developed During the Exercise
Normalised work developed during the exercise was derived as Work developed during the exercise/(\[60 X Maximum cross section of muscle\]-1100). Normalised work measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Normalised Work Developed During the Exercise | Baseline (Week 0) | 12.07 Joules/cm^2 |
| EGb 761® 120 mg | Normalised Work Developed During the Exercise | Week 12 | 9.23 Joules/cm^2 |
| EGb 761® 120 mg | Normalised Work Developed During the Exercise | Change from Baseline (Week 0) to Week 12 | -1.03 Joules/cm^2 |
| Placebo | Normalised Work Developed During the Exercise | Baseline (Week 0) | 12.00 Joules/cm^2 |
| Placebo | Normalised Work Developed During the Exercise | Week 12 | 11.53 Joules/cm^2 |
| Placebo | Normalised Work Developed During the Exercise | Change from Baseline (Week 0) to Week 12 | 0.47 Joules/cm^2 |
Secondary
Peak Post Exercise Perfusion
Peak post exercise perfusion (mL/mn/100 g of tissue) was assessed using Arterial spin labelling combined with Nuclear Magnetic Resonance imaging.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Peak Post Exercise Perfusion | Baseline (Week 0) | 54.30 ml/mn/100 g of tissue |
| EGb 761® 120 mg | Peak Post Exercise Perfusion | Week 12 | 58.80 ml/mn/100 g of tissue |
| EGb 761® 120 mg | Peak Post Exercise Perfusion | Change from Baseline (Week 0) to Week 12 | 3.60 ml/mn/100 g of tissue |
| Placebo | Peak Post Exercise Perfusion | Baseline (Week 0) | 51.80 ml/mn/100 g of tissue |
| Placebo | Peak Post Exercise Perfusion | Week 12 | 46.60 ml/mn/100 g of tissue |
| Placebo | Peak Post Exercise Perfusion | Change from Baseline (Week 0) to Week 12 | -1.55 ml/mn/100 g of tissue |
Secondary
Perfusion-time Integral During the First 9 Minutes Post Exercise.
The integral of 'peak perfusion' over a period of 9 minutes post exercise.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Perfusion-time Integral During the First 9 Minutes Post Exercise. | Baseline (Week 0) | 166.90 mL/100 g of tissue |
| EGb 761® 120 mg | Perfusion-time Integral During the First 9 Minutes Post Exercise. | Week 12 | 191.60 mL/100 g of tissue |
| EGb 761® 120 mg | Perfusion-time Integral During the First 9 Minutes Post Exercise. | Change from Baseline (Week 0) to Week 12 | -5.20 mL/100 g of tissue |
| Placebo | Perfusion-time Integral During the First 9 Minutes Post Exercise. | Baseline (Week 0) | 157.20 mL/100 g of tissue |
| Placebo | Perfusion-time Integral During the First 9 Minutes Post Exercise. | Week 12 | 185.70 mL/100 g of tissue |
| Placebo | Perfusion-time Integral During the First 9 Minutes Post Exercise. | Change from Baseline (Week 0) to Week 12 | 0.05 mL/100 g of tissue |
Secondary
Timed 25-foot Walk Test
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Timed 25-foot Walk Test | Baseline (Week 0) | 8.50 seconds |
| EGb 761® 120 mg | Timed 25-foot Walk Test | Week 12 | 9.00 seconds |
| EGb 761® 120 mg | Timed 25-foot Walk Test | Change from Baseline (Week 0) to Week 12 | 0.50 seconds |
| Placebo | Timed 25-foot Walk Test | Baseline (Week 0) | 6.75 seconds |
| Placebo | Timed 25-foot Walk Test | Week 12 | 6.75 seconds |
| Placebo | Timed 25-foot Walk Test | Change from Baseline (Week 0) to Week 12 | 0.00 seconds |
Secondary
Time to Peak Perfusion
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Time to Peak Perfusion | Baseline (Week 0) | 38.30 seconds |
| EGb 761® 120 mg | Time to Peak Perfusion | Week 12 | 39.80 seconds |
| EGb 761® 120 mg | Time to Peak Perfusion | Change from Baseline (Week 0) to Week 12 | 8.50 seconds |
| Placebo | Time to Peak Perfusion | Baseline (Week 0) | 58.55 seconds |
| Placebo | Time to Peak Perfusion | Week 12 | 76.55 seconds |
| Placebo | Time to Peak Perfusion | Change from Baseline (Week 0) to Week 12 | 14.25 seconds |
Secondary
Visual Assessment Scale (VAS) of Global Impression - Investigator
The VAS used a 10-cm scoring scale in which values were reported in mm such that 0=bad and 100=good. Total score range on VAS is from 0 to 100.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Visual Assessment Scale (VAS) of Global Impression - Investigator | Baseline (Week 0) | 78.0 mm |
| EGb 761® 120 mg | Visual Assessment Scale (VAS) of Global Impression - Investigator | Week 12 | 80.0 mm |
| EGb 761® 120 mg | Visual Assessment Scale (VAS) of Global Impression - Investigator | Change from Baseline (Week 0) to Week 12 | -2.0 mm |
| Placebo | Visual Assessment Scale (VAS) of Global Impression - Investigator | Baseline (Week 0) | 76.0 mm |
| Placebo | Visual Assessment Scale (VAS) of Global Impression - Investigator | Week 12 | 74.0 mm |
| Placebo | Visual Assessment Scale (VAS) of Global Impression - Investigator | Change from Baseline (Week 0) to Week 12 | -1.0 mm |
Secondary
Visual Assessment Scale (VAS) of Global Impression - Parents
The VAS used a 10-cm scoring scale in which values were reported in mm such that 0=bad and 100=good. Total score range on VAS is from 0 to 100.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Visual Assessment Scale (VAS) of Global Impression - Parents | Baseline (Week 0) | 64.0 mm |
| EGb 761® 120 mg | Visual Assessment Scale (VAS) of Global Impression - Parents | Week 12 | 64.0 mm |
| EGb 761® 120 mg | Visual Assessment Scale (VAS) of Global Impression - Parents | Change from Baseline (Week 0) to Week 12 | -7.0 mm |
| Placebo | Visual Assessment Scale (VAS) of Global Impression - Parents | Baseline (Week 0) | 62.0 mm |
| Placebo | Visual Assessment Scale (VAS) of Global Impression - Parents | Week 12 | 57.0 mm |
| Placebo | Visual Assessment Scale (VAS) of Global Impression - Parents | Change from Baseline (Week 0) to Week 12 | -10.0 mm |
Secondary
Visual Assessment Scale (VAS) of Global Impression - Patient
The VAS used a 10-cm scoring scale in which values were reported in mm such that 0=bad and 100=good. Total score range on VAS is from 0 to 100.
Time frame: Baseline (Week 0) to Week 12
Population: Due to small sample size and considering there are no specific studies in this population with EGb761; calculation with the use of a statistical hypothesis was not possible. Primary efficacy analyses performed on the mITT population and analysis of safety performed on the safety population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGb 761® 120 mg | Visual Assessment Scale (VAS) of Global Impression - Patient | Baseline (Week 0) | 60.0 mm |
| EGb 761® 120 mg | Visual Assessment Scale (VAS) of Global Impression - Patient | Week 12 | 67.0 mm |
| EGb 761® 120 mg | Visual Assessment Scale (VAS) of Global Impression - Patient | Change from Baseline (Week 0) to Week 12 | -2.0 mm |
| Placebo | Visual Assessment Scale (VAS) of Global Impression - Patient | Baseline (Week 0) | 68.5 mm |
| Placebo | Visual Assessment Scale (VAS) of Global Impression - Patient | Week 12 | 63.0 mm |
| Placebo | Visual Assessment Scale (VAS) of Global Impression - Patient | Change from Baseline (Week 0) to Week 12 | -2.0 mm |