Nilotinib in Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: Cohort 1:Nilotinib Oral Capsules (150mg or 300mg); Cohort 2: Nilotinib Oral Capsules (dose to be determined from Cohort 1); Placebo
Intervention description: 2 capsules taken once daily; 2 capsules taken once daily; 2 capsules taken once daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 76.0
Sex: All
Minimum age: 40 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: Northwestern; Nilotinib; USA; NILO-PD; Parkinson Disease

Summary:

      This study will assess the safety and tolerability of daily oral administration of nilotinib
      (150-300mg once daily) in Parkinson's Disease.
    

Eligibility criteria:

        Inclusion Criteria; Cohort 1 and 2:

          1. Idiopathic PD based on the UK Brain Bank diagnostic criteria.

          2. Any race and either gender, age 40-79

          3. Able to read and understand English with the capacity to provide voluntary informed
             consent by signing the informed consent form (ICF)

          4. Willing to comply with all study procedures including multiple lumbar punctures (LP)

          5. 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 < 4 in the
        ON state 8a. Must be on a stable regimen of PD medications, that includes levodopa, for at
        least 30 days prior to the screening visit

        a. Treatment with monoamine oxidase B (MAO-B) inhibitors will be allowed provided the dose
        has been stable for 60 days prior to baseline

        Inclusion criteria specific for Cohort 2:

        6b. Diagnosis of PD duration < 3 years 7b. H&Y stage ≤ 2 8b. Participants who are currently
        NOT receiving symptomatic therapy (ST) (levodopa,dopamine agonists and monoamine oxidase B
        (MAO-B) inhibitors) and NOT projected to require ST for at least 3 months from enrollment.

        a. Treatment with amantadine or an anticholinergic agent will be allowed provided the dose
        has been stable for 30 days prior to screening and will remain stable for the duration of
        the study

        Exclusion Criteria; Cohorts 1 and 2:

          1. Diagnosis of atypical parkinsonism

          2. History of bipolar disorder or major depression, or presence of active depression
             defined as a Beck Depression Inventory II (BDI-II) score >17

          3. History of a suicide attempt within the last 5 years or active suicidal ideations

          4. History of schizophrenia or schizophrenia spectrum disorders

          5. History of uncontrolled hypokalemia or hypomagnesaemia, or laboratory evidence of such
             on screening

          6. History of cardiac arrhythmia, long QT syndrome, or a corrected QT interval (QTcF)
             ≥450ms at screening visit 1

          7. Treated within 30 days prior to randomization, or planned use during the trial with
             any of the following classes of Concomitant drugs:

               1. Class IA or III antiarrhythmic drugs

               2. QT prolonging drugs

               3. Strong CYP3A4 inhibitors or inducers

               4. Anticoagulants

               5. Proton pump inhibitors

          8. A clinical history, or the active presence of a cardiovascular condition including:

               1. Myocardial infarction, known cardiac ischemia, or angina

               2. Cerebrovascular event (e.g. embolic stroke)

               3. 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

               4. History of Torsade de Pointes

               5. Other cardiovascular history that, in the opinion of the Site Investigator, will
                  preclude study participation

          9. 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

         10. History of epilepsy or a seizure within the last 6 months

         11. Active malignancy, or history of a neoplasm in the prior 5 years (excluding
             basal/squamous cell carcinoma)

         12. 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

         13. 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

         14. History of drug or alcohol abuse ≤ 5 years

         15. Active medical or psychiatric condition that in the opinion of the Site Investigator
             should preclude study participation

         16. Previous surgical management for PD

         17. Participants participating in any drug or device clinical investigation concurrently
             or within 30 days prior to screening for this study

         18. Severe lactose and galactose intolerance

         19. Participants with evidence of other significant laboratory abnormalities which in the
             opinion of the site investigator or clinical monitor should preclude study
             participation

         20. Known hypersensitivity or contraindication to study drugs (nilotinib or matching
             placebo) or their components.

         21. 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

         22. 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
        Assessment (MoCA) score < 21 at baseline

        Exclusion criteria specific for Cohort 2:

        22b.MoCA score < 26 at baseline 23b. Treated within 60 days prior to randomization or
        expected to require treatment within 3 months from randomization with any ST (including
        levodopa and dopamine agonists )

        a. Treatment with amantadine or an anticholinergic agent will be allowed provided the dose
        has been stable for 30 days prior to screening and will remain stable for the duration of
        the study