Procedures
ADVERSE EVENTS
Treatment was administered orally, in the morning, at fast. Patients received 4 bottles, each containing 15 tablets of active drug or placebo depending on the assigned treatment arm, every 2 weeks, for a planned duration of 18 weeks. Rapamycin plasma levels were regularly measured by high-performance liquid chromatography with tandem mass spectrometry (LC–MS/MS) and made known only to an independent monitor, who input rapamycin levels on a separate eCRF, allowing dose reduction if rapamycin plasma levels exceeded 12 ng/mL. A dose reduction could be asked also by caring neurologist directly through eCRF in case of adverse events (AEs) or reactions that, on clinical judgment, could be attributed to the study drug. After treatment end patients had to be followed up for further 36 weeks (