Safety parameters
early-infantile, adolescent/adult
ADVERSE EVENT, DISEASE, BLOOD, SECONDARY, EVENTS
Adverse events (serious and non-serious), concomitant drug and non-drug therapies, safety laboratory blood samples (hemoglobin, erythrocytes, hematocrit, thrombocytes, leukocytes, sodium, potassium, urea, creatinine, serum bilirubin level, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, follicle-stimulating hormone for postmenopausal women only), and urine samples (leukocytes, nitrite, urobilinogen, protein, pH, occult blood (erythrocytes, leucocytes), specific gravity, ketones, bilirubin, glucose) will be collected routinely throughout the study. Sparse pharmacokinetic blood sampling will be conducted in the Parent Study (visit 1–visit 6). Blood samples for the quantification of N-acetyl-L-leucine in plasma will be obtained at visit 7 and visit 9. Urine samples will also be collected for measuring concentrations of N-acetyl-D-leucine at the time points designated on the schedule of events (Suppl. Tables All statistical analyses will be detailed in a separate statistical analysis plan. For each of the primary and secondary endpoints, there will be evaluations within key subgroups: naïve versus non-naïve as determined at screening; age (pediatric versus adult at the time of enrollment); age/weight/dosing group; age of diagnosis: early-infantile (< 2 years), late-infantile (2 to < 6 years), juvenile (6 to < 15 years), adolescent/adult (≥ 15 years); disease severity based on SARA below/above the median SARA score at visit 1; gender (male versus female); region (US versus rest of world); patients taking miglustat versus patients not taking miglustat; intra-patient variability between SARA score at visit 1 (baseline 1) versus visit 2 (baseline 2) (below/above median). These evaluations will be based on plotting treatment differences together with 90% confidence intervals within each subgroup.In a one-sided test at the A description of data collection is provided in Suppl. Material 