Premium
Long‐Term Safety and Clinical Effects of Nilotinib in Parkinson's Disease
Author(s) -
Pagan Fernando L.,
Wilmarth Barbara,
TorresYaghi Yasar,
Hebron Michaeline L.,
Mulki Sanjana,
Ferrante Dalila,
Matar Sara,
Ahn Jaeil,
Moussa Charbel
Publication year - 2021
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28389
Subject(s) - nilotinib , tolerability , adverse effect , medicine , placebo , parkinson's disease , quality of life (healthcare) , clinical trial , disease , receptor , alternative medicine , nursing , pathology , tyrosine kinase
Background Nilotinib is US Food and Drug Administration–approved for leukemia, and this open‐label study investigated the safety, tolerability, and potential clinical effects of nilotinib in medically optimized patients with Parkinson's disease. Objectives Safety and tolerability were the primary objectives, and clinical outcomes were exploratory. Methods A total of 63 patients completed a 15‐month phase 2, double‐blind, placebo‐controlled study and were rerandomized 1:1 into an open‐label study of nilotinib 150 mg versus 300 mg for 12 months. Results Nilotinib was safe and tolerated, and no adverse effects seemed to be related to the drug, and no differences in adverse events were observed between groups. Exploratory clinical outcomes showed that nilotinib 300 mg was remarkably stable from baseline to 27 months using partial and total Unified Parkinson's Disease Scale (UPDRS). Nilotinib 150 mg versus 300 mg, significantly declined using partial or the sum of UPDRS Parts I and II. There was no significant difference in nilotinib 150 mg versus 300 mg using UPDRS Part III ( on levodopa) and total UPDRS Parts I to III. Subgroup analysis showed that late‐start nilotinib 150 mg significantly worsened using the sum of UPDRS Parts II + III and total UPDRS Parts I to III compared with late‐start nilotinib 300 mg. Quality of life using the Parkinson's Disease Questionnaire in nilotinib 150 mg significantly declined between 15 and 27 months compared with nilotinib 300 mg, and there was no change in cognition using the Montreal Cognitive Assessment between groups. Conclusions This study provides evidence that nilotinib is safe and tolerated in Parkinson's disease. The exploratory clinical data will inform an adequately powered larger study to evaluate the efficacy of nilotinib 300 mg in Parkinson's disease. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society