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| ID | Type | Description | Link |
|---|---|---|---|
| 2007-005371-34 | EudraCT Number |
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The purpose of this protocol is to determine the efficacy of EGb 761 120 mg bid versus placebo in patients suffering from Friedreich Ataxia
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EGb 761® 120 mg | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EGb 761 120 mg | Drug | EGb 761® 120 mg bid, orally for 12 to 14 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (Week 0) to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (Week 0) to Week 12 |
| Time to Peak Perfusion |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Necker Enfants Malades | Paris | 75015 | France |
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.
Patients were recruited at a single centre investigational site in France.
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| ID | Title | Description |
|---|---|---|
| FG000 | EGb 761® 120 mg | EGb 761 120 mg : EGb 761® 120 mg BID, orally for 12 to 14 weeks |
| FG001 | Placebo | Placebo : Placebo 1 tablet BID, orally for 12 to 14 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | EGb 761® 120 mg | EGb 761 120 mg : EGb 761® 120 mg BID, orally for 12 to 14 weeks |
| BG001 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Median | Full Range | pH per second | Baseline (Week 0) to Week 12 |
|
Not provided
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | EGb 761® 120 mg | EGb 761 120 mg : EGb 761® 120 mg BID, orally for 12 to 14 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Varicella | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director, Primary Care | Ipsen | clinical.trials@ipsen.com | clinical.trials@ipsen.com |
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| ID | Term |
|---|---|
| D005621 | Friedreich Ataxia |
| ID | Term |
|---|---|
| D013132 | Spinocerebellar Degenerations |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C063170 | Ginkgo biloba extract |
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| Placebo |
| Drug |
Placebo 1 tablet BID, orally for 12 to 14 weeks |
|
| Baseline (Week 0) to Week 12 |
| Perfusion-time Integral During the First 9 Minutes Post Exercise. | The integral of 'peak perfusion' over a period of 9 minutes post exercise. | Baseline (Week 0) to Week 12 |
| Muscle Reoxygenation Rate Post Exercise. | Muscle reoxygenation rate post exercise was assessed using Myoglobin Hydrogen-1 Nuclear Magnetic Resonance spectroscopy. | Baseline (Week 0) to Week 12 |
| 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) | Baseline (Week 0) to Week 12 |
| Developed Force During the Exercise Bout | Developed force during the exercise bout measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| 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). | Baseline (Week 0) to Week 12 |
| 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). | Baseline (Week 0) to Week 12 |
| 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). | Baseline (Week 0) to Week 12 |
| 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). | Baseline (Week 0) to Week 12 |
| Timed 25-foot Walk Test | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| 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. | Baseline (Week 0) to Week 12 |
| BG002 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Duration since first symptoms | Median | Full Range | years |
|
| Number of repeats of Guanine Adenine Adenine (GAA) sequence | Median | Full Range | GAA sequence repetitions |
|
Placebo : Placebo 1 tablet BID, orally for 12 to 14 weeks. |
|
|
|
| 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. | 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. | Posted | Median | Full Range | ml/mn/100 g of tissue | Baseline (Week 0) to Week 12 |
|
|
|
| Secondary | Time to Peak Perfusion | 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. | Posted | Median | Full Range | seconds | Baseline (Week 0) to Week 12 |
|
|
|
| Secondary | Perfusion-time Integral During the First 9 Minutes Post Exercise. | The integral of 'peak perfusion' over a period of 9 minutes post exercise. | 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. | Posted | Median | Full Range | mL/100 g of tissue | Baseline (Week 0) to Week 12 |
|
|
|
| Secondary | Muscle Reoxygenation Rate Post Exercise. | Muscle reoxygenation rate post exercise was assessed using Myoglobin Hydrogen-1 Nuclear Magnetic Resonance spectroscopy. | 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. | Posted | Median | Full Range | per second | Baseline (Week 0) to Week 12 |
|
|
|
| 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) | 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. | Posted | Median | Full Range | cm^2 | Baseline (Week 0) to Week 12 |
|
|
|
| Secondary | Developed Force During the Exercise Bout | Developed force during the exercise bout measured using Phosphorus 31 Nuclear Magnetic Resonance (P-31 NMR)spectroscopy | 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. | Posted | Median | Full Range | Joules | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | Joules/cm^2 | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | per second | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | score on a scale | Baseline (Week 0) to Week 12 |
|
|
|
| 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). | 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. | Posted | Median | Full Range | score on a scale | Baseline (Week 0) to Week 12 |
|
|
|
| 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). | 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. | Posted | Median | Full Range | score on a scale | Baseline (Week 0) to Week 12 |
|
|
|
| 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). | 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. | Posted | Median | Full Range | score on a scale | Baseline (Week 0) to Week 12 |
|
|
|
| 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). | 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. | Posted | Median | Full Range | score on a scale | Baseline (Week 0) to Week 12 |
|
|
|
| Secondary | Timed 25-foot Walk Test | 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. | Posted | Median | Full Range | seconds | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | seconds | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | seconds | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | millisecond | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | millisecond | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | mm | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | mm | Baseline (Week 0) to Week 12 |
|
|
|
| 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. | 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. | Posted | Median | Full Range | mm | Baseline (Week 0) to Week 12 |
|
|
|
| 1 |
| 11 |
| 8 |
| 11 |
| EG001 | 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. | 1 | 11 | 7 | 11 |
| Sciatica | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| Scoliosis | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| Fall | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
|
| Orthopedic procedure | Surgical and medical procedures | MedDRA 11.1 | Systematic Assessment |
|
Not provided
| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028361 | Mitochondrial Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Change from Baseline (Week 0) to Week 12 |
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| Change from Baseline (Week 0) to Week 12 |
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| Change from Baseline (Week 0) to Week 12 |
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