Nilotinib in Parkinson's Disease

Inclusion Criteria; Cohort 1 and 2:

• Idiopathic PD based on the UK Brain Bank diagnostic criteria.
• Any race and either gender, age 40-79
• Able to read and understand English with the capacity to provide voluntary informed consent by signing the informed consent form (ICF)
• Willing to comply with all study procedures including multiple lumbar punctures (LP)
• Must be on a stable regimen of central nervous system acting medications (if applicable) for at least 30 days prior to the baseline visit (e.g., benzodiazepines, antidepressants, hypnotics)

Inclusion criteria specific for Cohort 1:

6a. Diagnosis of PD duration > 5 year 7a. Hoehn & Yahr scale (H&Y) stage > 2 and 17

• History of a suicide attempt within the last 5 years or active suicidal ideations
• History of schizophrenia or schizophrenia spectrum disorders
• History of uncontrolled hypokalemia or hypomagnesaemia, or laboratory evidence of such on screening
• History of cardiac arrhythmia, long QT syndrome, or a corrected QT interval (QTcF) ≥450ms at screening visit 1
• Treated within 30 days prior to randomization, or planned use during the trial with any of the following classes of Concomitant drugs:
• Class IA or III antiarrhythmic drugs
• QT prolonging drugs
• Strong CYP3A4 inhibitors or inducers
• Anticoagulants
• Proton pump inhibitors
• A clinical history, or the active presence of a cardiovascular condition including:
• Myocardial infarction, known cardiac ischemia, or angina
• Cerebrovascular event (e.g. embolic stroke)
• Congestive heart failure, symptomatic first degree atrioventricular (AV) block or PR interval > 220msec and all second and third degree AV block, second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances
• History of Torsade de Pointes
• Other cardiovascular history that, in the opinion of the Site Investigator, will preclude study participation
• History of hepatic disease, including abnormal liver function defined as Total Bilirubin > 1.5 times upper limit, Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) > 2 times the upper limit of the normal, or coagulopathy with INR > 1.4
• History of epilepsy or a seizure within the last 6 months
• Active malignancy, or history of a neoplasm in the prior 5 years (excluding basal/squamous cell carcinoma)
• Prior history of pancreatitis or total gastrectomy or evidence of abnormal pancreatic function defined as elevated amylase and/or lipase > 2 times upper limit of normal
• Diagnosis of human immunodeficiency virus (HIV), clinically significant chronic hepatitis such as hepatitis B (HBV) or hepatitis C (HCV), or clinical history or signs of an active infection
• History of drug or alcohol abuse ≤ 5 years
• Active medical or psychiatric condition that in the opinion of the Site Investigator should preclude study participation
• Previous surgical management for PD
• Participants participating in any drug or device clinical investigation concurrently or within 30 days prior to screening for this study
• Severe lactose and galactose intolerance
• Participants with evidence of other significant laboratory abnormalities which in the opinion of the site investigator or clinical monitor should preclude study participation
• Known hypersensitivity or contraindication to study drugs (nilotinib or matching placebo) or their components.
• Female participants of child-bearing potential. Female participants must be post-menopausal, post-hysterectomy, or have a documented infertility based on a known medical or surgical condition
• Participants with a history of bone marrow suppression or evidence of persistent myelosuppression defined as absolute neutrophil count <1.8 X 109/L, significant anemia, or thrombocytopenia defined as platelet count < 100 X 109/L

Exclusion criteria specific for Cohort 1:

22a. Diagnosis of dementia based on the clinician's assessment, or a Montreal Cognitive A