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Development of a Disease Progression Model for Leucine‐Rich Repeat Kinase 2 in Parkinson's Disease to Inform Clinical Trial Designs
Author(s) -
Ahamadi Malidi,
Conrado Daniela J,
Macha Sreeraj,
Sinha Vikram,
Stone Julie,
Burton Jackson,
Nicholas Timothy,
Gallagher Jill,
Dexter David,
Bani Massimo,
Boroojerdi Babak,
Smit Hans,
Weidemann Jonas,
Chen Chao,
Yang Minhua,
Maciuca Romeo,
Lawson Rachael,
Burn David,
Marek Kenneth,
Venuto Charles,
Stafford Bob,
Akalu Mussie,
Stephenson Diane,
Romero Klaus
Publication year - 2020
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1634
Subject(s) - lrrk2 , medicine , clinical trial , disease , placebo , oncology , concomitant , parkinson's disease , pathology , alternative medicine
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 nonenriched 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.