Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis.
AuthorConrado, Daniela J
Watson, Ian A
Kern, Volker D
Stephenson, Diane T
MetadataShow full item record
CitationDopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis. 2018, 11 (1):63-70 Clin Transl Sci
Rights©2017 ASCPT. All rights reserved. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution License.
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AbstractGiven the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size.
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SponsorsParkinson's United Kingdom; AbbVie; Biogen; Eli Lilly; GE Healthcare; Lundbeck; Merck Sharp and Dohme; Pfizer; UCB; Michael J. Fox Foundation; Avid; Bristol-Myers Squibb; Convance; Genentech; GSK; Lilly; Merck; Meso Scale Discovery; Pfizer, Piramal; Roche; Sanofi Genzyme; Servier; TEVA; Golub Capital