Abstract
Given 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.
Highlights
Dopamine 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
Trial enrollment based purely on clinical criteria poses significant challenges given the high heterogeneity of symptoms and pathophysiology in patients with early-stage Parkinson’s disease (PD)
WHAT QUESTION DID THIS STUDY ADDRESS? ✔ It addressed the utility of dopamine transporter (DAT) neuroimaging as an enrichment biomarker in clinical trials targeting patients with early-stage PD
Summary
Dopamine 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. Dopamine 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. Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson’s Disease Clinical Trials: A Disease Progression Modeling Analysis. Trial enrollment based purely on clinical criteria poses significant challenges given the high heterogeneity of symptoms and pathophysiology in patients with early-stage PD. HOW THIS MIGHT CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE ✔ Exclusion of SWEDD subjects (DAT imaging-based enrichment) from future clinical trials will improve the chance of determining clinical benefit of new drug candidates against PD at a reduced trial size, and prevent exposure to experimental treatments of patients who are unlikely to experience disease progression. 11% subjects without evidence of dopamine transporter (DAT) deficit (SWEDD) were enrolled in the failed Parkinson Research Examination of CEP-1347 Trial (PRECEPT), presenting minimal clinical or imaging changes over time.[5]
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