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

NCT02954978 | Unknown Phase 2 DMC

• 1 other identifier: IRB# 2016-0380
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Parkinson's disease (PD) is the second most common neurodegenerative disorder causing motor and non-motor symptoms. PD is characterized by death of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta and formation of inclusions known as Lewy bodies (LBs) that primarily contain aggregated alpha-Synuclein. Nilotinib (Tasigna®, AMN107, Novartis, Switzerland) is approved by U.S. Food and Drug Administration (FDA) and is well tolerated for CML treatment at oral doses of 600-800mg daily. Nilotinib penetrates the brain and promotes autophagic degradation of alpha-Synuclein and p-Tau, leading to survival of DA neurons and improvement of motor function in PD models. For these studies, Nilotinib (1-10mg/kg daily) was used at significantly less than the clinically approved dose (up to 1200mg daily) in CML.

Conditions

Parkinson Disease; Parkinsons Disease With Dementia

Outcome Measures

Primary Outcomes (1)

• Safety will be measured by number of participants experiencing the occurrence of adverse events and/or abnormal laboratory values

  Safety will be measured by assessing number of participants with abnormal laboratory values, as well as adverse events (AEs) and serious adverse events (SAEs) deemed to be possibly, probably, or definitely related to the study drug.

  12 months

Secondary Outcomes (1)

• Effects of nilotinib treatment on levels of homovanillic acid in cerebrospinal fluid

  12 months

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Out of seventy five (75) participants that will be recruited and randomly assigned 1:1:1 to the three (3) groups (arms), 25 patients in group 1 will receive the placebo ("sugar pill") one (1) capsule by mouth once daily (taken without a meal) for 12 months and 3 months follow up.

Drug: Placebo Oral Capsule

Nilotinib 150mg

ACTIVE COMPARATOR

Out of seventy five (75) participants that will be recruited and randomly assigned 1:1:1 to the three (3) groups (arms), 25 patients in group 2 will receive 150mg Nilotinib one (1) capsule once daily (taken without a meal) for 12 months and 3 months follow up.

Drug: Nilotinib 150mg oral capsule [Tasigna]

Nilotinib 300mg

ACTIVE COMPARATOR

Out of seventy five (75) participants that will be recruited and randomly assigned 1:1:1 to the three (3) groups (arms), 25 patients in group 3 will receive 300mg Nilotinib one (1) capsule once daily (taken without a meal) for 12 months and 3 months follow up.

Drug: Nilotinib 300mg oral capsule [Tasigna]

Interventions

Placebo Oral Capsule DRUG

25 patients in group 1 will receive Placebo ("sugar pill") one (1) capsule once daily (taken without a meal) for 12 months and 3 months follow up.

Also known as: Placebo

Placebo

Nilotinib 150mg oral capsule [Tasigna] DRUG

25 patients in group 2 will receive 150mg Nilotinib one (1) capsule once daily (taken without a meal) for 12 months and 3 months follow up.

Also known as: Nilotinib low dose

Nilotinib 150mg

Nilotinib 300mg oral capsule [Tasigna] DRUG

25 patients in group 3 will receive 300mg Nilotinib one (1) capsule once daily (taken without a meal) for 12 months and 3 months follow up.

Also known as: Nilotinib high dose

Nilotinib 300mg

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative (LAR).
• Patients between the age of 40-90 years, medically stable
• Diagnosis of PD according to the UK Brain Bank Diagnostic Criteria
• PD subjects with MoCA ≥ 22
• ≥Hoehn and Yahr stage ≤3
• No mono-amine oxidase (MAO)-B inhibitors (Selegeline or rasagiline) are allowed at least 6 weeks before enrollment
• Must be medically stable on 800mg Levodopa daily for at least 4 weeks
• QTc interval 350-460 ms, inclusive
• Participants must be willing to undergo LP at baseline and 12 months after treatment

You may not qualify if:

• Patients with hypokalemia, hypomagnesaemia, or long QT syndrome- QTc≥461 ms
• Concomitant drugs known to prolong the QTc interval and history of any cardiovascular disease, including myocardial infraction or cardiac failure, angina, arrhythmia
• 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
• 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.
• Abnormal liver function defined as AST and/or ALT \> 100% the upper limit of the normal
• Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal

Sponsors & Collaborators

• Georgetown University: lead

Study Sites (1)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Related Publications (4)

• Pagan F, Hebron M, Valadez EH, Torres-Yaghi Y, Huang X, Mills RR, Wilmarth BM, Howard H, Dunn C, Carlson A, Lawler A, Rogers SL, Falconer RA, Ahn J, Li Z, Moussa C. Nilotinib Effects in Parkinson's disease and Dementia with Lewy bodies. J Parkinsons Dis. 2016 Jul 11;6(3):503-17. doi: 10.3233/JPD-160867.

  PMID: 27434297 RESULT

• Joshi D, Kulkarni M, Parekh P, Shah S, Greig NH, Acharya S. Targeting protein kinases in Parkinson's disease: the emerging role of phytoconstituents. Nutr Neurosci. 2025 Dec;28(12):1532-1563. doi: 10.1080/1028415X.2025.2531356. Epub 2025 Jul 18.

  PMID: 40680102 DERIVED

• Fowler AJ, Ahn J, Hebron M, Chiu T, Ayoub R, Mulki S, Ressom H, Torres-Yaghi Y, Wilmarth B, Pagan FL, Moussa C. CSF MicroRNAs Reveal Impairment of Angiogenesis and Autophagy in Parkinson Disease. Neurol Genet. 2021 Nov 12;7(6):e633. doi: 10.1212/NXG.0000000000000633. eCollection 2021 Dec.

  PMID: 34786477 DERIVED

• Pagan FL, Hebron ML, Wilmarth B, Torres-Yaghi Y, Lawler A, Mundel EE, Yusuf N, Starr NJ, Anjum M, Arellano J, Howard HH, Shi W, Mulki S, Kurd-Misto T, Matar S, Liu X, Ahn J, Moussa C. Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial. JAMA Neurol. 2020 Mar 1;77(3):309-317. doi: 10.1001/jamaneurol.2019.4200.

  PMID: 31841599 DERIVED

Related Links

• https://sites.google.com/a/georgetown.edu/moussa-lab/home3

MeSH Terms

Conditions

Parkinson Disease

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Fernando L Pagan, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Neurology Co-Director, Movement Disorders Program Director, NPF Center of Excellence Associate Professor, SOM Clinical Track

Study Record Dates

• First Submitted: November 1, 2016
• First Posted: November 4, 2016
• Study Start: January 1, 2017
• Primary Completion: May 1, 2020
• Study Completion: July 1, 2020
• Last Updated: March 14, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)