Amendment 1 was written primarily to: increase the overall sample size from 350 to 430 subjects, including an increase to 70 subjects/group in stage 1 of enrollment and an increase to 75 subjects/group in stage 2 of enrollment; delete randomization lock to review eligibility from the study design; revise stability inclusion criterion number 6 to allow hospitalized subjects if they were stable and hospitalized for social reasons; add an inclusion criterion for male contraception requirements; increase the maximum allowable body mass index and include a weight limit; specify a daily dose for oral haloperidol in the list of medications associated with TdP; delete administration of the Abnormal Involuntary Movement Scale, Barnes Akathisia Rating Scale, and Simpson-Angus Scale at Screening Visit 1; specify the level of interaction needed between social workers, case managers, or site staff and the subject to qualify as an informant; clarify the qualification of an informant for scales such as the SCoRS and Specific Levels of Functioning Scale; clarify cutoff value for a negative serum cotinine test for a subject's inclusion in the study; add that drug and alcohol screening could be performed onsite during the screening period; clarify that the informant only completed section number 4 of the Modified Client Socio-demographic and Service Receipt Inventory; delete the need to administer ABT-126 "preferably with food"; clarify expectations for and documentation of investigational product storage conditions; add the optional use of Automated Directly Observed Therapy and Directly Observed Therapy at sites in the United States that opted to take part in additional compliance measures; correct administrative errors; and, correct other errors.

Amendment 2 was written primarily to: update the number of sites from approximately 50 to approximately 70 sites; delete the ability of the medical monitor to allow a subject who met QT interval corrected for heart rate using the Fridericia formula discontinuation criteria to continue in the study; add orphenadrine, procyclidine, and biperiden to the list of restricted anticholinergics and update throughout the protocol that anticholinergic use was prohibited for the 2 weeks prior to randomization; update Table 2; delete the specification that body temperature must have been taken orally; clarify the timing of electrocardiogram (ECG) in relation to timing of blood collections; specify that serum pregnancy test was performed by the central laboratory; add mean corpuscular volume and bicarbonate to Table 3; update description on how to handle and process samples collected for ABT-126 assay; update the scoring derivations for UPSA-2ER in Table 9; and make administrative changes to the protocol.

Amendment 3 was written primarily to: increase the age range upper limit from 55 to 65 years; delete the exclusion of subjects based on their concomitant use of anticholinergic medications; clarify AbbVie's review of key eligibility criteria and sites' screening data entry responsibilities; delete the exclusion of subjects who had participated in a previous study with ABT-126; expand the list of allowable antipsychotics to include conventional antipsychotics; allow a subject to be randomized based on a negative urine cotinine test at Screening Visit 2 if the serum cotinine test result was not available at Day –1; update the timing of pharmacokinetic sample collection relative to the cognitive and functional assessments as well as the timing of ECG relative to blood sample collection, allowing the site to manage the most appropriate order of procedures based on the length of visit and time of day that the visit took place; add urine screening test for cotinine at Screening Visit 1; revise instructions for cognitive testing to ensure that scales were administered at approximately the same time of day throughout the subject's participation; update the plan for labeling the investigational product, stipulating that a separate set of investigational product was to be packaged for Romania with single panel clinical drug labels; clarify that serious adverse events were to be reported to AbbVie via fax only if the site did not have access to the electronic data capture (EDC) system or the EDC system was not operable; clarify rater requirements and expectations; and, make administrative changes to the protocol.

Amendment 4 was written primarily to: clarify that while all medical safety screening procedures scheduled for Screening Visit 1 were to be performed within 42 days prior to the Day –1 visit, if > 42 days elapsed between Screening Visit 1 and the scheduled Day –1 visit, the timing for repeating medical safety screening procedures was flexible as long as the results were reviewed to confirm eligibility prior to randomization; allow alternative sources to confirm eligibility for subjects when there was difficulty obtaining medical records; emphasize the need to enter the subject's psychiatric and medical history, concomitant medications, and screening psychiatric symptom scale data into the EDC system prior to randomization; allow retesting and further clinical evaluation of subjects with certain screening laboratory abnormalities; modify exclusion criteria to avoid excluding subjects who had laboratory abnormalities but not a clinical diagnosis of liver disease or renal insufficiency; exclude subjects who were previously randomized in this study; allow the medical monitor to review suitability if subject completed participation in another clinical trial within the past 3 months prior to Screening Visit 1; add use of the Clinical Trial Subject database to identify and exclude subjects who had recently or were currently participating in other clinical trials; clarify allowed antipsychotics agents; indicate that dose or medication changes of allowed antipsychotic medications during treatment period were permitted and recommended that dose change should be communicated to AbbVie; clarify that use of all anticholinergics for treatment of extrapyramidal symptoms was restricted; add footnotes to Table 2 for clarity; clarify that AbbVie approval was needed for repeat of screening labs and additional lab tests not required by the protocol; clarify that AbbVie personnel could know the ABT-126 dose selected for the second stage of randomization; and, make other minor changes.

Amendment 5 was written primarily to change the primary efficacy variable from the standard MCCB composite score to the MCCB neurocognitive composite score and include the standard MCCB composite score as a secondary efficacy variable.