Pivotal Study of N-acetyl-L-leucine for CACNA1A

Scale for the Assessment and Rating of Ataxia

The Scale for Assessment and Rating of Ataxia has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test. The range is 0-40 points, with a lower score representing neurological improvement and a higher score representing neurological worsening.

Spinocerebellar Ataxia Functional Index (SCAFI)

Spinocerebellar Ataxia Functional Index (SCAFI) is composed of 8 Meter Walk Test, 9-Hole Peg Test of Dominant and Non-Dominant Hand (9HPT-D/9HPT-ND) (the 3 tests are timed assessments; each is done twice and values are averaged; the 8MWT and 9HPT-D and 9HPT-ND values are converted from times to rates, and the results expressed as a composite Z-score of each test relative to baseline) and the PATA rate (counted number how often a patient can repeat the syllables "PATA" within 10 seconds), a measure of speech performance. The scores of these 3 were transformed to Z-scores (=individual's average of both trials to perform the respective task - mean of study population at baseline) / SD of study population at baseline). A Z-score of 0 equates to the population mean at baseline. For all 3, higher Z-scores (above mean) mean better performance. The SCAFI total score was calculated as the arithmetic mean of the non-missing Z-scores for the 3. A higher total score means better performance.

Physician's / Caregiver's / Patient's Clinical Global Impressions (CGI)

The Clinical Global Impression of Improvement assessed by the investigator/caregiver/patient is evaluated on a 7 point Likert scale ranging from 1='very much improved' to 7='very much worse'

EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale

For posting, health-related quality of life based on the EQ-5D visual analogue scale (VAS) was presented as a secondary endpoint. EQ-5D VAS is a 0-100 scale where patients are asked to indicate their overall health, with a score of 0 indicating worst health and a score of 100 indicating best health.

Neuro Quality of Life - Upper Extremity Function (NeuroQOL-UEF)

The Neurology Quality of Life (NeuroQOL) Upper Extremity Function (UEF) scale is a self-report of health-related quality of life that measures the patient's ability to carry out various activities involving digital, manual, and reach-related functions, ranging from fine motor to self-care (activities of daily living). The NeuroQOL scale is approximately a 100-point scale, where 100 is the best functioning, and 0 is the worst.

Scale for Ocular Motor Disorders in Ataxia

The Scale for Ocular Motor Dysfunction in Ataxia (SODA) is a 7-item clinical rating scale (ocular alignment, saccadic intrusions, jerk nystagmus, vestibulo-ocular reflex (VOR) cancellation, ocular pursuit, VOR, and saccades) evaluating the extend of ocular motor deficits in cerebellar disorders. The scale ranges from range -26, where 0 is the best status and 26 is the worst).

Epworth Sleepiness Scale

The Epworth Sleepiness Scale is a self-administered questionnaire with 8 questions. Patients (or the caregiver on the patient's behalf) are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most people engage in these activities at least occasionally, although not necessarily every day. The Epworth Sleepiness Scale score (the sum of 8 item scores, 0-3) can range from 0 to 24.

Frequency of Seizures

Patients and their caregivers will be asked to keep a diary of the frequency of seizures. Specifically, they will note the number of attacks of seizures, and days with seizures per week.

Frequency of Migraine Attacks

Patients and their caregivers will be asked to keep a diary of the frequency of migraines. Specifically, they will note the number of attacks of migraine, aura, and days with headache (including migraine) per week.