Important changes to the protocol set forth by Amendment 1 include: * Australia was added. * The number of proposed sites was increased. * The number of subjects to be randomized was increased. * A fixed-block randomization was to be done within each country. * The study design was modified to a group sequential clinical trial design. * The following extensions were made to the study design: - The Double-blind Treatment Period was extended. This included a 4-week dose optimization period and a dose maintenance period that was increased; - The study period was extended; - The number of visits was increased. * The total duration of the study was increased * A definition for inadequate response to MPH therapy was added. * Secondary objectives were added: - To assess the impact of SPD489 compared to STRATTERA on the perception of health state preferences via the HUI-2. - To monitor subject safety via the BPRS-C, the C-SSRS, and the UKU-SERS-Clin. * The study schedule was modified to include the HUI-2, BPRS-C, C-SSRS, and UKU-SERS-Clin assessments and to specify at what visits these were to be performed. * A section describing the suitability of the subject to remain in the study was added. * The safety follow-up was changed from a phone call to a site visit. * Assessments performed at the Safety Follow-up Visit (Visit 10) were specified. * An upward dose titration limit of 100mg STRATTERA was added for subjects weighing >/= 70kg. * A chronic or current tic disorder or history of tics was added as an exclusion criterion. * Additional subjects were to be recruited if more than 20% of subjects were prematurely discontinued. * A window of ±2 hour was added for dosing. * The number of capsules taken per visit was specified based on subject weight. * It was specified that the ADHD-RS-IV was to be completed by a physician. * The assumed cumulative response rates for each treatment group were updated. * An external DSMB was added.

Important changes to the protocol set forth by Amendment 2 include: * Australia was removed. * Randomization was to be stratified by country. * The definition of inadequate response to MPH therapy was modified. * The Screening Period was to be from Day -14 to Day -3. * Down-titration was to only occur within the first 4 weeks. * Electrocardiogram was added as a safety endpoint. * Clarification that the change from baseline in the ADHD-RS-IV Total Score was a secondary endpoint. * The following changes involved inclusion or exclusion criteria: - Subjects using a standard dose of inhaled beta-agonist were allowed study entry; - Subjects who had taken >1 MPH or who previously had intolerable side effects to 1 or more MPH treatments were excluded; - Subjects with intermittent passive suicidal ideation were not necessarily excluded; - Subjects with a known CYP2D6 poor metabolizer genotype were excluded; - Subjects with a known penicillin allergy were excluded; - Subjects with current or anticipated inpatient care were excluded; - Subjects taking medications that caused orthostatic hypotension were excluded. * An Enrolled Population was added. * Assessment scales were to be administered by the same person, as appropriate, whenever possible. * Certain assessments (ADHD-RS-IV, CGI, physical examination, BPRS-C, C-SSRS, and UKU-SERS-Clin) were to be performed by a qualified rater/individual. * The external DSMB was renamed to DMC. * The internal DMC was renamed to DRC. * Subjects who were prematurely discontinued from the study were to be censored at Visit 9. * A supportive analysis was performed on the cumulative proportion of ADHD-RS-IV responders based on LOCF rather than observed data. * HUI-2 and WFIRS-P were recategorized as a health outcome and a functional outcome, respectively. * ANCOVA for ADHD-RS-IV Total Score was to include country as a blocking factor. * The definition of a treatment-emergent AE was expanded.