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Nilotinib Safety and Clinical Effects on 'ON' Disability in Parkinson's Disease Patients

130 Pages Posted: 3 Jun 2019

See all articles by Charbel Moussa

Charbel Moussa

Georgetown University - Translational Neurotherapeutics Program (TNP)

Fernando Pagan

Georgetown University - Translational Neurotherapeutics Program (TNP)

Yasar Torres-Yaghi

Georgetown University - Translational Neurotherapeutics Program (TNP)

Ellen Valladez

Georgetown University - Translational Neurotherapeutics Program (TNP)

Abigail Lawler

Georgetown University - Translational Neurotherapeutics Program (TNP)

Michaeline Hebron

Georgetown University - Translational Neurotherapeutics Program (TNP)

Jaeil Ahn

Georgetown University - Translational Neurotherapeutics Program (TNP); Georgetown University - Department of Biostatistics, Bioinformatics and Biomathematics (DBBB)

Sorell Schwartz

Georgetown University - Translational Neurotherapeutics Program (TNP)

Barbara Wilmarth

Georgetown University - Translational Neurotherapeutics Program (TNP)

Ashot Shekonyan

Georgetown University - Translational Neurotherapeutics Program (TNP)

Helen Howard

Georgetown University - Translational Neurotherapeutics Program (TNP)

More...

Abstract

Background: Parkinson's disease (PD) involves motor and non-motor symptoms and loss of brain dopamine neurons. Nilotinib is a tyrosine kinase inhibitor that may alter brain dopamine metabolism.

Methods: A phase II randomized, double-blind, placebo controlled trial to evaluate Nilotinib effects on safety, tolerability and clinical outcomes in PD. Seventy-five participants were randomized 1:1:1 into placebo, 150mg or 300mg Nilotinib once daily for 12 months. This study evaluated Nilotinib effects on top of the optimal standard of care in mid-stage PD (H&Y 2.5-3) at 6 and 12 months.

Findings: Participants well tolerated Nilotinib and rare hematological, hepatic and other systems disorders were observed. Cardiovascular events were seen in all groups. Prior to randomization all participants were stabilized on either Levodopa and/or dopamine agonists and were tested ON time. As expected, all 3 groups were stable at 6 months, indicating the effects of PD medications. However, the placebo group declined on UPDRS II (2.39 points, p=0.007), total UPDRS I-III (4.78 points, p=0.031) and UPDRS I-IV (4.47 points, p=0.038) at 6-12 months but Nilotinib groups remained stable. Similarly, all groups were stable on PDQ39 SI and the emotional well-being subscale at 6 months but the placebo group declined (8.17 points, p=0.001 and 1.7 points, p=0.003, respectively) at 6-12 months, while Nilotinib groups remained stable.

Interpretation: Nilotinib is well tolerated and appears to be safe in PD patients. Nilotinib appears to stop the decline in motor and non-motor functions up to 12 months, while the effects of optimized PD medications significantly wear off six months after treatment. Nilotinib may have a significant impact on the care and management of PD patients, leading to delay or elimination of dose adjustment of PD-medications, thus avoiding their side effects.

Trial Registration: The study was conducted under FDA Investigational New Drug (IND) # 123183, and registered in ClinicalTrials.gov (NCT02954978).

Funding Statement: Lasky and Barajas Family Fund and other philanthropies. Novartis Pharmaceuticals Corporation provided the study drug.

Declaration of Interests: Charbel Moussa is an inventor on several US and International Georgetown University patents to use Nilotinib and other tyrosine kinase inhibitors as a treatment for neurodegenerative diseases. No other authors declare any conflict of interests with this study.

Ethics Approval Statement: This study was conducted in accordance with Good Clinical Practice guidelines and was approved by the Institutional Review Board (IRB# 2016-0380) at Georgetown University Medical Center as well as by Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS) scientific review board. Informed consent was obtained from all participants and study partners

Keywords: Nilotinib, PD, "ON' time, UPDRS, PDQ39, ADL, QoL

Suggested Citation

Moussa, Charbel and Pagan, Fernando and Torres-Yaghi, Yasar and Valladez, Ellen and Lawler, Abigail and Hebron, Michaeline and Ahn, Jaeil and Schwartz, Sorell and Wilmarth, Barbara and Shekonyan, Ashot and Howard, Helen, Nilotinib Safety and Clinical Effects on 'ON' Disability in Parkinson's Disease Patients (May 29, 2019). Available at SSRN: https://ssrn.com/abstract=3397207 or http://dx.doi.org/10.2139/ssrn.3397207

Charbel Moussa (Contact Author)

Georgetown University - Translational Neurotherapeutics Program (TNP) ( email )

Washington, DC
United States

Fernando Pagan

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Yasar Torres-Yaghi

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Ellen Valladez

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Abigail Lawler

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Michaeline Hebron

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Jaeil Ahn

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Georgetown University - Department of Biostatistics, Bioinformatics and Biomathematics (DBBB)

4000 Reservoir Rd., NW
Washington, DC
United States

Sorell Schwartz

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Barbara Wilmarth

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Ashot Shekonyan

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

Helen Howard

Georgetown University - Translational Neurotherapeutics Program (TNP)

Washington, DC
United States

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