Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Parkinson's Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02954978
• Date of registration: 01/11/2016
• Prospective Registration: Yes
• Primary sponsor: Georgetown University
• Public title: Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Parkinson's Disease PD Nilotinib
• Scientific title: A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Low Doses of Nilotinib Treatment on Safety, Tolerability, Pharmacokinetics and Biomarkers in Parkinson's Disease
• Date of first enrolment: January 2017
• Target sample size: 75
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02954978
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Fernando L Pagan, MD
• Affiliation: Georgetown University

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Written informed consent

2. Capable of providing informed consent and complying with study procedures. Subjects
who are unable to provide consent may use a Legally Authorized Representative (LAR).

3. Patients between the age of 40-90 years, medically stable

4. Diagnosis of PD according to the UK Brain Bank Diagnostic Criteria

5. PD subjects with MoCA = 22

6. 2.5 =Hoehn and Yahr stage =3

7. No mono-amine oxidase (MAO)-B inhibitors (Selegeline or rasagiline) are allowed at
least 6 weeks before enrollment

8. Must be medically stable on 800mg Levodopa daily for at least 4 weeks

9. QTc interval 350-460 ms, inclusive

10. Participants must be willing to undergo LP at baseline and 12 months after treatment

Exclusion Criteria:

1. Patients with hypokalemia, hypomagnesaemia, or long QT syndrome- QTc=461 ms

2. Concomitant drugs known to prolong the QTc interval and history of any cardiovascular
disease, including myocardial infraction or cardiac failure, angina, arrhythmia

3. History or presence of cardiac conditions including:

- Cardiovascular or cerebrovascular event (e.g. myocardial infarction, unstable
angina, or stroke)

- Congestive heart failure

- First, second- or third-degree atrioventricular block, sick sinus syndrome, or
other serious cardiac rhythm disturbances

- Any history of Torsade de Pointes

4. Treatment with any of the following drugs at the time of screening or the preceding 30
days, and/or planned use over the course of the trial:

- Treatment with Class IA or III antiarrhythmic drugs (e.g. quinidine)

- Treatment with QT prolonging drugs (www.crediblemeds.org)- excluding Selective
Serotonin Reuptake Inhibitors (SSRIs) (e.g. Citalopram, Paxil, Zoloft, Cymbalta,
Sertraline, etc...)

- Strong CYP3A4 inhibitors (including grapefruit juice). The concomitant use of
strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin,
atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir,
telithromycin, voriconazole) must be avoided. Grapefruit products may also
increase serum concentrations of Nilotinib. Should treatment with any of these
agents be required, therapy with Nilotinib should be interrupted.

- Anticoagulants, including Coumadin (warfarin), heparin, enoxaparin, daltiparin,
xarelto, etc.

- St. John's Wort and the concomitant use of strong other CYP3A4 inducers (e.g.,
dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine,
phenobarbital) must be avoided since these agents may reduce the concentration of
Nilotinib.

5. Abnormal liver function defined as AST and/or ALT > 100% the upper limit of the normal

6. Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of
normal

7. History of HIV, clinically significant chronic hepatitis, or other active infection

8. Females must not be lactating, pregnant or with possible pregnancy

9. Medical history of liver or pancreatic disease

10. Clinical signs indicating syndromes other than idiopathic PD, including corticobasal
degeneration, supranuclear gaze palsy, multiple system atrophy, chronic traumatic
encephalopathy, signs of frontal dementia, history of stroke, head injury or
encephalitis, cerebellar signs, early severe autonomic involvement, Babinski sign

11. Current evidence or history in past two years of epilepsy, focal brain lesion, head
injury with loss of consciousness or DSM-IV criteria for any major psychiatric
disorder including psychosis, major depression, bipolar disorder, alcohol or substance
abuse

12. Evidence of any significant clinical disorder or laboratory finding that renders the
participant unsuitable for receiving an investigational drug including clinically
significant or unstable hematologic, hepatic, cardiovascular, pulmonary,
gastrointestinal, endocrine, metabolic, renal or other systemic disease or laboratory
abnormality

13. Active neoplastic disease, history of cancer five years prior to screening, including
breast cancer (history of skin melanoma or stable prostate cancer are not
exclusionary)

14. Contraindications to LP: prior lumbosacral spine surgery, severe degenerative joint
disease or deformity of the spine, platelets < 100,000, use of Coumadin/warfarin, or
history of a bleeding disorder

15. Must not be on any immunosuppressant medications (e.g. IVig)

16. Must not be enrolled as an active participant in another clinical study

17. Diagnosis of DLB



Age minimum: 40 Years
Age maximum: 90 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Parkinsons Disease With Dementia

Intervention(s)

Drug: Placebo Oral Capsule

Drug: Nilotinib 300mg oral capsule [Tasigna]

Drug: Nilotinib 150mg oral capsule [Tasigna]

Primary Outcome(s)

Safety will be measured by number of participants experiencing the occurrence of adverse events and/or abnormal laboratory values [Time Frame: 12 months]

Secondary Outcome(s)

Effects of nilotinib treatment on levels of homovanillic acid in cerebrospinal fluid [Time Frame: 12 months]

Secondary ID(s)

IRB# 2016-0380

Source(s) of Monetary Support

Please refer to primary and secondary sponsors