Parkinson Disease
Conditions
Keywords
Northwestern, Nilotinib, USA, NILO-PD, Parkinson Disease
Brief summary
This study will assess the safety and tolerability of daily oral administration of nilotinib (150-300mg once daily) in Parkinson's Disease.
Detailed description
The purpose of this study is to determine if nilotinib is safe, if it can be tolerated by patients with Parkinson's disease (PD) and to learn if nilotinib has the possibility of effectively treating PD symptoms. Nilotinib has been approved by the Food and Drug Administration (FDA) to treat certain types of cancer (leukemia) but is considered investigational in this study because it has not been approved for treating PD. Twenty-five sites will enroll participants into 2 cohorts,approximately 75 in Cohort 1 and 60 in Cohort 2. Participants with moderate to advanced PD symptoms will be enrolled in Cohort 1, randomly assigned to take nilotinib (150 mg or 300mg) or placebo, and will complete 13 in-person study visits over 8.5 months. The results from Cohort 1 will determine if either dose of nilotinib (150mg or 300 mg) is safe and tolerable enough to move forward and evaluate in Cohort 2. If either dose is found to be safe and tolerable, participants with early PD will be enrolled into Cohort 2. Participants in Cohort 2 will be randomly assigned to either nilotinib (dose to be determined from Cohort 1 results) or placebo and will complete 17 in-person visits over 14.5 months. For both cohorts, the study visits will include clinical assessment of motor, neuropsychiatric and cognitive testing as well as collection of blood and cerebral spinal fluid, collected by lumbar puncture. This study will also evaluate if nilotinib can help improve motor symptoms associated with PD. All participants in Cohort 1 and participants in Cohort 2 who have started PD medications will have an assessment of the motor exam (Part III) in a practically defined OFF state (12 hours post dose) and ON state (at least one-hour post dose).
Interventions
DRUGCohort 1:Nilotinib Oral Capsules (150mg or 300mg)
2 capsules taken once daily
DRUGCohort 2: Nilotinib Oral Capsules (dose to be determined from Cohort 1)
2 capsules taken once daily
DRUGPlacebo
2 capsules taken once daily
Sponsors
University of Rochester
University of Iowa
Michael J. Fox Foundation for Parkinson's Research
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 79 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of Nilotinib Over Placebo | 6 months | The count of study participants who completed the 6-month study treatment period while active on their original assigned dose |
| Safety of Nilotinib | We assessed adverse events that were collected from the first dose of study drug until 60 days after the participant's last dose. | The count of study participants who experienced any treatment-related SAE in each treatment group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in MDS-UPDRS Part III | The MDS-UPDRS Part III ON state was collected at baseline, day 14, day 30, month 3, month 6, 30 and 60 days post treatment. The OFF state was collected at baseline, month 3, month 6, 30 and 60 days post treatment. | The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III is a motor examination in both practically defined medications OFF state (12 hrs post dose) and ON state (based on the participant/site investigator defined best ON and/or approximately 1 hour post dose). Measure Description: The part III subscale score ranges from 0-165. The Larger the value stands for more disability from PD. |
Countries
United States
Participant flow
Recruitment details
From November 2017 to December 2018, 125 patients were assessed for eligibility. Of those screened, 76 participants were enrolled in the trial.
Pre-assignment details
Of the patients assessed for eligibility, 49 (39%) were excluded. 42 patients did not meet inclusion criteria and 7 declined study participation.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo enclosed in capsules to maintain the blind was administered orally once per day over the course of 6 months. | 25 |
| Nilotinib 150 Patients were administered 1 capsule of 150 mg Nilotinib and 1 capsule of matching placebo each day over the course of 6 months. | 25 |
| Nilotinib 300 Patients were administered 2 capsules of 150 mg Nilotinib each day over the course of 6 months. | 26 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 4 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Nilotinib 150 | Total | Placebo | Nilotinib 300 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 38 Participants | 12 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 38 Participants | 13 Participants | 9 Participants |
| Age, Continuous | 61.2 years STANDARD_DEVIATION 7.4 | 64.6 years STANDARD_DEVIATION 7.5 | 65.5 years STANDARD_DEVIATION 6.8 | 66.9 years STANDARD_DEVIATION 7.3 |
| BDI-II | 7.3 units on a scale STANDARD_DEVIATION 5.4 | 6.8 units on a scale STANDARD_DEVIATION 4.8 | 6.6 units on a scale STANDARD_DEVIATION 4.9 | 6.6 units on a scale STANDARD_DEVIATION 4.3 |
| DRS-2 | 137.8 units on a scale STANDARD_DEVIATION 7.8 | 137.9 units on a scale STANDARD_DEVIATION 6.6 | 138.1 units on a scale STANDARD_DEVIATION 5.7 | 137.7 units on a scale STANDARD_DEVIATION 6.3 |
| Education Adjusted MoCA Score | 27.4 units on a scale STANDARD_DEVIATION 1.9 | 27.1 units on a scale STANDARD_DEVIATION 2.2 | 26.9 units on a scale STANDARD_DEVIATION 2.4 | 27.0 units on a scale STANDARD_DEVIATION 2.4 |
| EQ-5D EQ-5D Health Score | 71.5 units on a scale STANDARD_DEVIATION 23.3 | 72.8 units on a scale STANDARD_DEVIATION 21.5 | 70.6 units on a scale STANDARD_DEVIATION 25.1 | 76.0 units on a scale STANDARD_DEVIATION 15.9 |
| EQ-5D EQ-5D Summary Index | 0.83 units on a scale STANDARD_DEVIATION 0.13 | 0.80 units on a scale STANDARD_DEVIATION 0.14 | 0.79 units on a scale STANDARD_DEVIATION 0.14 | 0.78 units on a scale STANDARD_DEVIATION 0.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 74 Participants | 24 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Levodopa Equivalent Daily Dose | 971.8 mg STANDARD_DEVIATION 251.4 | 1016.9 mg STANDARD_DEVIATION 398.7 | 1066.5 mg STANDARD_DEVIATION 519.7 | 1012.5 mg STANDARD_DEVIATION 390.5 |
| MDS-UPDRS Total Score MDS-UPDRS Total OFF Score | 65.0 units on a scale STANDARD_DEVIATION 16 | 66.4 units on a scale STANDARD_DEVIATION 19.3 | 63.8 units on a scale STANDARD_DEVIATION 21.3 | 70.2 units on a scale STANDARD_DEVIATION 20.2 |
| MDS-UPDRS Total Score MDS-UPDRS Total ON Score | 46.9 units on a scale STANDARD_DEVIATION 15.1 | 48.4 units on a scale STANDARD_DEVIATION 16.2 | 46.2 units on a scale STANDARD_DEVIATION 17.8 | 51.9 units on a scale STANDARD_DEVIATION 15.7 |
| Modified S/E ADL Modified S/E ADL OFF | 77.3 units on a scale STANDARD_DEVIATION 17.8 | 75.8 units on a scale STANDARD_DEVIATION 16.8 | 73.2 units on a scale STANDARD_DEVIATION 16.5 | 77.0 units on a scale STANDARD_DEVIATION 14.9 |
| Modified S/E ADL Modified S/E ADL ON | 92.2 units on a scale STANDARD_DEVIATION 5.8 | 88.6 units on a scale STANDARD_DEVIATION 12.2 | 86.8 units on a scale STANDARD_DEVIATION 8.7 | 87.0 units on a scale STANDARD_DEVIATION 17.9 |
| Parkinson's Disease Classifications Class of Symptomatic Therapy, MAOB Inhibitors | 8 Participants | 31 Participants | 11 Participants | 12 Participants |
| Parkinson's Disease Classifications Hoehn and Yahr Stage 0-2 | 5 Participants | 10 Participants | 4 Participants | 1 Participants |
| Parkinson's Disease Classifications Hoehn and Yahr Stage 3 | 20 Participants | 66 Participants | 21 Participants | 25 Participants |
| Parkinson's Disease History Age at Diagnosis | 52.7 years STANDARD_DEVIATION 7.6 | 54.7 years STANDARD_DEVIATION 8 | 56.2 years STANDARD_DEVIATION 6.8 | 55.2 years STANDARD_DEVIATION 9.3 |
| Parkinson's Disease History Parkinson's Disease Duration | 8.5 years STANDARD_DEVIATION 3.2 | 9.9 years STANDARD_DEVIATION 4.7 | 9.4 years STANDARD_DEVIATION 4.9 | 11.7 years STANDARD_DEVIATION 5.2 |
| PDQ-39 | 19.0 units on a scale STANDARD_DEVIATION 9.4 | 18.8 units on a scale STANDARD_DEVIATION 10.8 | 19.0 units on a scale STANDARD_DEVIATION 12.7 | 18.4 units on a scale STANDARD_DEVIATION 10.3 |
| PDSS | 115.3 units on a scale STANDARD_DEVIATION 11.6 | 108.3 units on a scale STANDARD_DEVIATION 18.3 | 106.6 units on a scale STANDARD_DEVIATION 21.8 | 103.2 units on a scale STANDARD_DEVIATION 18.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 23 Participants | 72 Participants | 24 Participants | 25 Participants |
| Region of Enrollment United States | 25 participants | 76 participants | 25 participants | 26 participants |
| Sex: Female, Male Female | 10 Participants | 24 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 15 Participants | 52 Participants | 16 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 | 0 / 26 |
| other Total, other adverse events | 22 / 25 | 23 / 25 | 23 / 26 |
| serious Total, serious adverse events | 2 / 25 | 1 / 25 | 1 / 26 |
Outcome results
Primary
Safety of Nilotinib
The count of study participants who experienced any treatment-related SAE in each treatment group
Time frame: We assessed adverse events that were collected from the first dose of study drug until 60 days after the participant's last dose.
Population: Intent-to-treat population, all randomized subjects. The counts refer to the number of participants that experienced an SAE in each treatment arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Safety of Nilotinib | 2 Participants |
| Nilotinib 150 mg | Safety of Nilotinib | 1 Participants |
| Nilotinib 300 mg | Safety of Nilotinib | 1 Participants |
p-value: 0.568995% CI: [0.0451, 5.489]Regression, Poisson
p-value: 0.61Fisher Exact
p-value: 0.59495% CI: [0.0472, 5.7409]Regression, Poisson
p-value: 1Fisher Exact
Primary
Tolerability of Nilotinib Over Placebo
The count of study participants who completed the 6-month study treatment period while active on their original assigned dose
Time frame: 6 months
Population: Intent-to-treat population, all randomized subjects per arm. The Count of participants below are the number of participants that met the criteria for analysis of tolerability.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Tolerability of Nilotinib Over Placebo | 21 Participants |
| Nilotinib 150 mg | Tolerability of Nilotinib Over Placebo | 19 Participants |
| Nilotinib 300 mg | Tolerability of Nilotinib Over Placebo | 20 Participants |
p-value: 0.3626Fisher Exact
p-value: 0.3895Fisher Exact
Secondary
Change in MDS-UPDRS Part III
The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III is a motor examination in both practically defined medications OFF state (12 hrs post dose) and ON state (based on the participant/site investigator defined best ON and/or approximately 1 hour post dose). Measure Description: The part III subscale score ranges from 0-165. The Larger the value stands for more disability from PD.
Time frame: The MDS-UPDRS Part III ON state was collected at baseline, day 14, day 30, month 3, month 6, 30 and 60 days post treatment. The OFF state was collected at baseline, month 3, month 6, 30 and 60 days post treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in MDS-UPDRS Part III | Month 3 MDS-UPDRS Part III (OFF) | 37.92 units on a scale | Standard Deviation 14.46 |
| Placebo | Change in MDS-UPDRS Part III | 30 Day Post MDS-UPDRS Part III (ON) | 20.52 units on a scale | Standard Deviation 8.82 |
| Placebo | Change in MDS-UPDRS Part III | Day 30 MDS-UPDRS Part III (ON) | 22.36 units on a scale | Standard Deviation 10 |
| Placebo | Change in MDS-UPDRS Part III | 60 Day Post MDS-UPDRS Part III (OFF) | 37.36 units on a scale | Standard Deviation 14.2 |
| Placebo | Change in MDS-UPDRS Part III | Month 6 MDS-UPDRS Part III (ON) | 19.63 units on a scale | Standard Deviation 9.86 |
| Placebo | Change in MDS-UPDRS Part III | Month 3 MDS-UPDRS Part III (ON) | 19.83 units on a scale | Standard Deviation 9.23 |
| Placebo | Change in MDS-UPDRS Part III | 30 Day Post MDS-UPDRS Part III (OFF) | 38.92 units on a scale | Standard Deviation 14.15 |
| Placebo | Change in MDS-UPDRS Part III | Baseline MDS-UPDRS Part III (OFF) | 40.36 units on a scale | Standard Deviation 13.51 |
| Placebo | Change in MDS-UPDRS Part III | Baseline MDS-UPDRS Part III (ON) | 22.80 units on a scale | Standard Deviation 8.85 |
| Placebo | Change in MDS-UPDRS Part III | Month 6 MDS-UPDRS Part III (OFF) | 36.21 units on a scale | Standard Deviation 14.91 |
| Placebo | Change in MDS-UPDRS Part III | 60 Day Post MDS-UPDRS Part III (ON) | 20.88 units on a scale | Standard Deviation 10.88 |
| Placebo | Change in MDS-UPDRS Part III | Day 14 MDS-UPDRS Part III (ON) | 23.13 units on a scale | Standard Deviation 11.29 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | Month 3 MDS-UPDRS Part III (ON) | 24.88 units on a scale | Standard Deviation 13.7 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | 30 Day Post MDS-UPDRS Part III (OFF) | 41.48 units on a scale | Standard Deviation 12.19 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | 60 Day Post MDS-UPDRS Part III (OFF) | 40.27 units on a scale | Standard Deviation 11.33 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | Baseline MDS-UPDRS Part III (ON) | 24.76 units on a scale | Standard Deviation 11.62 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | Day 14 MDS-UPDRS Part III (ON) | 27.58 units on a scale | Standard Deviation 13.53 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | Day 30 MDS-UPDRS Part III (ON) | 26.84 units on a scale | Standard Deviation 13.08 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | Month 6 MDS-UPDRS Part III (OFF) | 41.91 units on a scale | Standard Deviation 13.4 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | Month 6 MDS-UPDRS Part III (ON) | 24.43 units on a scale | Standard Deviation 11.5 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | 30 Day Post MDS-UPDRS Part III (ON) | 25.13 units on a scale | Standard Deviation 12.26 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | 60 Day Post MDS-UPDRS Part III (ON) | 23.91 units on a scale | Standard Deviation 12.93 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | Baseline MDS-UPDRS Part III (OFF) | 42.84 units on a scale | Standard Deviation 12.53 |
| Nilotinib 150 mg | Change in MDS-UPDRS Part III | Month 3 MDS-UPDRS Part III (OFF) | 39.92 units on a scale | Standard Deviation 12.41 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | 30 Day Post MDS-UPDRS Part III (OFF) | 45.26 units on a scale | Standard Deviation 14.13 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | 30 Day Post MDS-UPDRS Part III (ON) | 26.79 units on a scale | Standard Deviation 9.1 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | Baseline MDS-UPDRS Part III (ON) | 25.15 units on a scale | Standard Deviation 8.17 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | Month 6 MDS-UPDRS Part III (OFF) | 43.96 units on a scale | Standard Deviation 11.62 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | 60 Day Post MDS-UPDRS Part III (ON) | 26.42 units on a scale | Standard Deviation 10.58 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | 60 Day Post MDS-UPDRS Part III (OFF) | 43.00 units on a scale | Standard Deviation 13.63 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | Month 3 MDS-UPDRS Part III (OFF) | 41.04 units on a scale | Standard Deviation 13.38 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | Month 3 MDS-UPDRS Part III (ON) | 25.76 units on a scale | Standard Deviation 8.71 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | Day 30 MDS-UPDRS Part III (ON) | 29.73 units on a scale | Standard Deviation 10.83 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | Baseline MDS-UPDRS Part III (OFF) | 43.50 units on a scale | Standard Deviation 14.01 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | Month 6 MDS-UPDRS Part III (ON) | 25.61 units on a scale | Standard Deviation 8.93 |
| Nilotinib 300 mg | Change in MDS-UPDRS Part III | Day 14 MDS-UPDRS Part III (ON) | 29.33 units on a scale | Standard Deviation 9.77 |
Comparison: The key secondary objective is to conduct a futility analysis within each treatment group which examines the observed change in the MDS-UPDRS Part III ON within the two dose groups compared to previously reported changes from the Pagan et al (2016) study (NCT02281474).p-value: 0.0001Mixed Models Analysis
Comparison: The key secondary objective is to conduct a futility analysis within each treatment group which examines the observed change in the MDS-UPDRS Part III ON within the two dose groups compared to previously reported changes from the Pagan et al (2016) study (NCT02281474).p-value: 0.0001Mixed Models Analysis
Comparison: Additional secondary objective #1 is to establish the degree of symptomatic effect of Nilotinib as measured by the change in the MDS\_UPDRS Part III ON score between baseline and 1 month.p-value: 0.031Mixed Models Analysis
Comparison: Additional secondary objective #2 is to establish the degree of symptomatic effect of Nilotinib as measured by the change in the MDS\_UPDRS Part III ON score between the final visit on study drug and 30 days off study drug.p-value: 0.47Mixed Models Analysis
Comparison: Additional secondary objective #3 is to assess the impact of Nilotinib on the progression of PD disability as measured by the change in the MDS\_UPDRS Part III ON score between baseline and 6 months.p-value: 0.077Mixed Models Analysis
Comparison: Additional secondary objective #3 is to assess the impact of Nilotinib on the progression of PD disability as measured by the change in the MDS\_UPDRS Part III OFF score between baseline and 6 months.p-value: 0.17Mixed Models Analysis