Rajesh Pahwa1, Stuart Isaacson2, Joohi Jimenez-Shaheed3, Irene A Malaty4, Andres Deik5, Reed Johnson6, Rajiv Patni7. 1. Department of Neurology, University of Kansas Medical Center, Kansas City, KS, 66160, USA. Electronic address: rpahwa@kumc.edu. 2. Parkinson's Disease and Movement Disorders Center, 951 NW 13th Street, Building 5-E, Boca Raton, FL, 33486, USA. Electronic address: isaacson@parkinsonscenter.org. 3. Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, McNair Campus, 7200 Cambridge Street, 9th Floor, MS: BCM609, Houston, TX, 77030, USA. Electronic address: jshahed@bcm.edu. 4. University of Florida, 3450 Hull Road, 4th Floor, Gainesville, FL, USA. Electronic address: irene.malaty@neurology.ufl.edu. 5. Department of Neurology, Parkinson's Disease and Movement Disorders Center, University of Pennsylvania, 330 South 9th Street, 3rd Floor Neurology, Philadelphia, 19107, PA, USA. Electronic address: Andres.DeikAcostaMadiedo@uphs.upenn.edu. 6. Adamas Pharmaceuticals, Inc., 1900 Powell Street Suite 750, Emeryville, CA, 94608, USA. Electronic address: rjohnson@adamaspharma.com. 7. Adamas Pharmaceuticals, Inc., 1900 Powell Street Suite 750, Emeryville, CA, 94608, USA. Electronic address: rpatni@adamaspharma.com.
Abstract
INTRODUCTION: In Parkinson's disease, dyskinesias result from disease progression and chronic levodopa therapy. Using Unified Dyskinesia Rating Scale (UDysRS) data pooled from two pivotal trials of ADS-5102 (amantadine) extended-release capsules in dyskinetic patients, we assessed the impact of dyskinesia on activities of daily living (ADLs), and the effects of ADS-5102 versus placebo. METHODS:Patients had troublesome dyskinesia (≥1 h/day) and at least mild functional impact of dyskinesia per Movement Disorder SocietyUnified Parkinson's Disease Rating Scale, Part IV, item 4.2. UDysRS Parts 1B, 3, and 4 scores at baseline were summarized descriptively. Twelve-week changes in score distributions and total scores were tested for significant differences between treatments. RESULTS: Among 196 patients, the majority (63%-73%) characterized their dyskinesia at baseline as having at least a mild impact on walking and balance; public and social settings; exciting or emotional settings; doing hobbies and other activities; handwriting; and dressing (six of ten ADLs in UDysRS Part 1B). By clinician ratings (in Parts 3 and 4), greatest impairment was most often observed in the trunk (62% of patients) and occurred most often for the ADL of dressing (64% had at least moderate impairment). ADS-5102 significantly reduced the patient-rated impact of dyskinesia on six of ten ADLs in Part 1B, the clinician-rated intensity of dyskinesia in all seven body regions assessed in Part 3, and the clinician-rated disability during three of four ADL tasks assessed in Part 4. Improvements in Parts 1B, 3, and 4 total scores were also statistically significant. CONCLUSION:Dyskinesia can impair multiple tasks of daily living. Further studies may help characterize its underreported impact. By several measures, ADS-5102 treatment was associated with significant improvement of dyskinesias.
RCT Entities:
INTRODUCTION: In Parkinson's disease, dyskinesias result from disease progression and chronic levodopa therapy. Using Unified Dyskinesia Rating Scale (UDysRS) data pooled from two pivotal trials of ADS-5102 (amantadine) extended-release capsules in dyskineticpatients, we assessed the impact of dyskinesia on activities of daily living (ADLs), and the effects of ADS-5102 versus placebo. METHODS:Patients had troublesome dyskinesia (≥1 h/day) and at least mild functional impact of dyskinesia per Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part IV, item 4.2. UDysRS Parts 1B, 3, and 4 scores at baseline were summarized descriptively. Twelve-week changes in score distributions and total scores were tested for significant differences between treatments. RESULTS: Among 196 patients, the majority (63%-73%) characterized their dyskinesia at baseline as having at least a mild impact on walking and balance; public and social settings; exciting or emotional settings; doing hobbies and other activities; handwriting; and dressing (six of ten ADLs in UDysRS Part 1B). By clinician ratings (in Parts 3 and 4), greatest impairment was most often observed in the trunk (62% of patients) and occurred most often for the ADL of dressing (64% had at least moderate impairment). ADS-5102 significantly reduced the patient-rated impact of dyskinesia on six of ten ADLs in Part 1B, the clinician-rated intensity of dyskinesia in all seven body regions assessed in Part 3, and the clinician-rated disability during three of four ADL tasks assessed in Part 4. Improvements in Parts 1B, 3, and 4 total scores were also statistically significant. CONCLUSION:Dyskinesia can impair multiple tasks of daily living. Further studies may help characterize its underreported impact. By several measures, ADS-5102 treatment was associated with significant improvement of dyskinesias.
Authors: Mallory L Hacker; Maxim Turchan; Lauren E Heusinkveld; Amanda D Currie; Sarah H Millan; Anna L Molinari; Peter E Konrad; Thomas L Davis; Fenna T Phibbs; Peter Hedera; Kevin R Cannard; Li Wang; David Charles Journal: Neurology Date: 2020-06-29 Impact factor: 11.800
Authors: Felipe Patricio; Alan Axel Morales-Andrade; Aleidy Patricio-Martínez; Ilhuicamina Daniel Limón Journal: Front Pharmacol Date: 2020-12-15 Impact factor: 5.810