A Clinically Important Difference (CID) for the Unified Dyskinesia Rating Scale (UDysRS) Total Score Change in Parkinson's Disease (PD) Patients with Dyskinesia

Objective: To identify a CID for the UDysRS total score in the pivotal trials of ADS-5102 (amantadine) extended release capsules in PD patients with dyskinesia. Background: In the pivotal trials (EASE LID (NCT02136914) and EASE LID 3 (NCT02274766)), mean UDysRS total score improvements from baseline to week 12 were significantly greater with bedtime administration of ADS-5102 (GOCOVRI™) (−15.9 and −20.7) than with placebo (PBO) (−8.0 and −6.3). We determined a CID for the UDysRS using the Clinical Global Impression of Change (CGI-C) as the anchor. Design/Methods: The per-subject changes from baseline to week 12 in the UDysRS that simultaneously optimized the sensitivity (S) and specificity (Sp) to at least minimal (CGI-C ≥ 1), moderate (CGI-C ≥2) and marked (CGI-C ≥ 3) improvements. These per-subjects changes were obtained from the empirical receiver operating characteristic curve generated using the pooled treatment arms in EASE LID. Response rates for at least each level of improvement were then obtained by treatment group and confirmed using EASE LID 3. Pooled response rates are presented here. Results: In EASE LID (N=121), decreases from baseline to week 12 in the UDysRS of -9, -10 and -20 were associated with at least minimal (S=74%, Sp=65%), moderate (S=75%, Sp=61%) and marked (S=80%, Sp=80%) improvements in the CGI-C, respectively. Using these cut-offs: the responder rates (pooled studies) for ADS-5102 (N=100) vs PBO (N=96) were: 69% vs 46%, 67% vs 41% and 44% vs 17% for at least minimal, moderate and marked improvement, respectively. Conclusions: These empirical evaluations suggest that a decrease of at least 9 units in the UDysRS is a CID which is consistent with at least minimal improvements in the CGI-C. Importantly, decreases from baseline to week 12 in the UDysRS met CID criteria for most subjects (~70%) treated with ADS-5102. Study Supported by: Adamas Pharmaceuticals, Inc. Disclosure: Dr. Pahwa has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, ACADIA, Acorda, Adamas, Cynapses, Global Kinetics, Lundbeck, Neurocrine, Pfizer, Sage, Sunovion, Teva Neuroscience and US World Meds. Dr. Pahwa has received research support from Abbvie, Adamas, Avid, Biotie, Boston Scientific, Civitas, Cynapses, Kyowa, National Parkinson Foundation, NIH/NINDS, Parkinson Study Group. Dr. Tanner has nothing to disclose. Dr. Hauser has nothing to disclose. Dr. Isaacson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultancy and/or promotional speaker fees: Acadia, Acorda, Adamas, Allergan, Amarantus, Biotie, Britannia, Cynapsus, GE Pharma, Impax, Ipsen, Kyowa, Lundbeck, Teva, UCB, and US WorldMeds. Research funding: AbbVie, Acadia, Acorda, Adamas, Addex, Allergan. Dr. Johnson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Adamas Pharmaceuticals, Inc. Dr. Felt has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Adamas Pharmaceuticals, Inc. Dr. Patni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Adamas Pharmaceuticals, Inc. Dr. Llorens has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Adamas Pharmaceuticals, Inc.