1. Development of a Disease Progression Model for Leucine‐Rich Repeat Kinase 2 in Parkinson's Disease to Inform Clinical Trial Designs
- Author
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Romeo Maciuca, Rachael A Lawson, Timothy Nicholas, David T. Dexter, Malidi Ahamadi, Chao Chen, David J. Burn, Kenneth Marek, Minhua Yang, Klaus Romero, Bob Stafford, Sreeraj Macha, Julie A. Stone, Diane Stephenson, Jackson Burton, Daniela J. Conrado, Vikram Sinha, Hans Smit, Massimo Bani, Mussie Akalu, Jill Gallagher, Babak Boroojerdi, Jonas Weidemann, and Charles S. Venuto
- Subjects
Adult ,Male ,Research design ,Oncology ,medicine.medical_specialty ,Parkinson's disease ,Disease ,Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ,030226 pharmacology & pharmacy ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Aged ,Aged, 80 and over ,Pharmacology ,Clinical Trials as Topic ,business.industry ,Incidence (epidemiology) ,Parkinson Disease ,Middle Aged ,Models, Theoretical ,medicine.disease ,LRRK2 ,Clinical trial ,Research Design ,030220 oncology & carcinogenesis ,Concomitant ,Mutation ,Disease Progression ,Female ,business ,Cohort study - Abstract
A quantitative assessment of Parkinson’s disease (PD) progression is critical for optimizing clinical trials design. Disease progression model was developed using pooled data from the Progression Marker Initiative study and the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson’s Disease study. Age, gender, concomitant medication, and study arms were predictors of baseline. A mutation in the leucine-rich repeat kinase 2 (LRRK2) encoding gene was associated with the disease progression rate. The progression rate in subjects with PD who carried LRRK2 mutation was slightly slower (~0.170 points/month) than that in PD subjects without the mutation (~0.222 points/month). For a non-enriched placebo-controlled clinical trial, approximately 70 subjects/arm would be required to detect a drug effect of 50% reduction in the progression rate with 80% probability. Whereas, 85, 93 and 100 subjects/arm would be required for an enriched clinical trial with 30%, 50% and 70% subjects with LRRK2 mutations, respectively.
- Published
- 2019
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