Tiago A Mestre1, Isabelle Beaulieu-Boire2, Camila C Aquino3, Nicolas Phielipp4, Yu Yan Poon3, Jane P Lui5, Julie So3, Susan H Fox3. 1. Movement Disorders Centre and Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Division of Neurology, University of Toronto, Ontario, Canada; The Parkinson's Disease and Movement Disorder Centre, Division of Neurology, Department of Medicine, The Ottawa Hospital, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Electronic address: tmestre@toh.on.ca. 2. Movement Disorders Centre and Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Division of Neurology, University of Toronto, Ontario, Canada; Division of Neurology, Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada. 3. Movement Disorders Centre and Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Division of Neurology, University of Toronto, Ontario, Canada. 4. Movement Disorders Centre and Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Division of Neurology, University of Toronto, Ontario, Canada; Department of Neurology (Movement Disorders), University of California Irvine, Irvine, CA, USA. 5. Movement Disorders Centre and Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, Division of Neurology, University of Toronto, Ontario, Canada; University Health Network, Toronto Western Hospital, Department of Pharmacy, Toronto, Ontario, Canada.
Abstract
INTRODUCTION: Dyskinesia remain a significant problem in Parkinson Disease (PD). The translation process of novel drug targets for dyskinesia has proven difficult with several failures at phase III level. Determining the 'clinically important change' (CIC) for dyskinesia rating scales in phase II clinical trials may assist in optimizing drug development of new anti-dyskinetic treatments. We used a standard phase IIa acute levodopa infusion paradigm to determine for the first time the CIC for dyskinesia using the new UDysRS. METHODS: We performed a randomized, double-blind, placebo-controlled crossover study with eleven PD patients with stable bothersome dyskinesia. We used the following patient-reported clinically important events as CIC anchors: onset, maximum intensity, remission of dyskinesia. Objective dyskinesia scores using the UDysRS part III Impairment were determined at these same events by blinded video-rating. The CIC was determined using the 'within-patient' score change and a sensitivity- and specificity-based approach. RESULTS: Patients were most aware of 'onset of dyskinesia', followed by 'remission of dyskinesia'. An 11.1-point median change (UDysRS Part III Impairment, p < 0.0001) was the CIC for patient-reported remission of dyskinesia from a practically defined-OFF state. A 2.32-point change (UDysRS Part III Impairment) had the best specificity and sensitivity to distinguish between patient-reported remission and perception of dyskinesia. CONCLUSIONS: In this study, we provide the first report of a CIC for the UDysRS Part III Impairment. Early knowledge of a CIC may help inform the decision to advance into phase III trials and contribute for a higher yield of success in finding new anti-dyskinetic treatments.
RCT Entities:
INTRODUCTION:Dyskinesia remain a significant problem in Parkinson Disease (PD). The translation process of novel drug targets for dyskinesia has proven difficult with several failures at phase III level. Determining the 'clinically important change' (CIC) for dyskinesia rating scales in phase II clinical trials may assist in optimizing drug development of new anti-dyskinetic treatments. We used a standard phase IIa acute levodopa infusion paradigm to determine for the first time the CIC for dyskinesia using the new UDysRS. METHODS: We performed a randomized, double-blind, placebo-controlled crossover study with eleven PDpatients with stable bothersome dyskinesia. We used the following patient-reported clinically important events as CIC anchors: onset, maximum intensity, remission of dyskinesia. Objective dyskinesia scores using the UDysRS part III Impairment were determined at these same events by blinded video-rating. The CIC was determined using the 'within-patient' score change and a sensitivity- and specificity-based approach. RESULTS:Patients were most aware of 'onset of dyskinesia', followed by 'remission of dyskinesia'. An 11.1-point median change (UDysRS Part III Impairment, p < 0.0001) was the CIC for patient-reported remission of dyskinesia from a practically defined-OFF state. A 2.32-point change (UDysRS Part III Impairment) had the best specificity and sensitivity to distinguish between patient-reported remission and perception of dyskinesia. CONCLUSIONS: In this study, we provide the first report of a CIC for the UDysRS Part III Impairment. Early knowledge of a CIC may help inform the decision to advance into phase III trials and contribute for a higher yield of success in finding new anti-dyskinetic treatments.
Authors: Rejko Krüger; Jochen Klucken; Daniel Weiss; Lars Tönges; Pierre Kolber; Stefan Unterecker; Michael Lorrain; Horst Baas; Thomas Müller; Peter Riederer Journal: J Neural Transm (Vienna) Date: 2017-03-24 Impact factor: 3.575
Authors: Eric Freire-Alvarez; Egon Kurča; Lydia Lopez Manzanares; Eero Pekkonen; Cleanthe Spanaki; Paola Vanni; Yang Liu; Olga Sánchez-Soliño; Luigi M Barbato Journal: Mov Disord Date: 2021-07-08 Impact factor: 9.698