The main purpose of this substantial amendment was to include the suicidality risk assessment (Columbia-Suicide Severity Rating Scale [C-SSRS]). In accordance with the recently issued US Food and Drug Administration (FDA) draft Guidance for Industry, which went into effect on 29 Oct 2010, the C-SSRS has been added to all ongoing and new interventional protocols in order to prospectively assess the occurrence of treatment-emergent suicidality in clinical studies of drug and biological products (FDA, Guidance for Industry, 2010). In addition, a list of Anticipated serious adverse events (SAEs) was included in this amendment in compliance with the US FDA guidance on safety reporting requirements for studies conducted under an open Investigational New Drug Application (effective 28 Mar 2011; FDA, Guidance for Industry and Investigators, 2010). The Beck Depression Inventory II and the Beck Anxiety Inventory were removed from the study assessments. Other changes included in this amendment were as follows: -Added the timeframe at which the efficacy and other variables were analyzed. -Added the version number of the Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale. -Updated the storage requirements for the rotigotine patch. -Clarified the subject eligibility for SP1005 based on the dosing requirements from the previous rotigotine study (ie, SP1004). -Permitted the use of a topical anesthetic prior to the needle stick. -Added safety parameters (12-lead electrocardiogram [ECG] and laboratory tests) to be performed at the investigator’s discretion at the Unscheduled Visit. -Removed reference to patch size from all sections, except in Section 7.1 of the Protocol, Description of investigational medicinal product. -Revised the preparation and handling of the blood and saliva samples and clearly identified the PK sampling visits. -Updated sponsor clinical project manager contact information. -Corrected typographic errors and made changes of an editorial nature.

The main purpose of this substantial amendment was to ensure consistency between the protocol and the US FDA Pediatric Development Plan for the RLS indication in subjects 13 years and older. Since the subject’s dosing was no longer dependent on body weight, the dosing schedules for each study period were revised. In addition, PK saliva sampling was removed from the study. Data from a completed PK study (RL0002) suggested that saliva concentrations of rotigotine could not be used as a surrogate for plasma concentrations of rotigotine. Other changes included in this amendment were as follows: -Updated the contact information for SAE reporting and procedures for reporting SAEs to be consistent with the current protocol template. -Updated the regulatory status of rotigotine for the treatment of RLS in adults in the US. -Clarified that the sample size may be increased if adolescent subjects with RLS were to roll over into this study from other future rotigotine studies. -Removed the requirement for PK blood samples to be centrifuged at a controlled temperature. -Corrected typographic errors and minor inconsistencies of an editorial nature.