Toggle Main Menu Toggle Search

Open Access padlockePrints

Development of a disease progression model for leucine-rich repeat kinase 2 in Parkinson's disease to inform clinical trial designs

Lookup NU author(s): Dr Rachael LawsonORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley, 2020.

For re-use rights please refer to the publisher's terms and conditions.


A quantitative assessment of Parkinson’s disease (PD) progression is critical for optimizing clinicaltrials design. Disease progression model was developed using pooled data from the ProgressionMarker Initiative study and the Incidence of Cognitive Impairment in Cohorts with LongitudinalEvaluation in Parkinson’s Disease study. Age, gender, concomitant medication, and study arms werepredictors of baseline. A mutation in the leucine-rich repeat kinase 2 (LRRK2) encoding gene wasassociated with the disease progression rate. The progression rate in subjects with PD who carriedLRRK2 mutation was slightly slower (~0.170 points/month) than that in PD subjects without themutation (~0.222 points/month). For a non-enriched placebo-controlled clinical trial, approximately70 subjects/arm would be required to detect a drug effect of 50% reduction in the progression ratewith 80% probability. Whereas, 85, 93 and 100 subjects/arm would be required for an enrichedclinical trial with 30%, 50% and 70% subjects with LRRK2 mutations, respectively.

Publication metadata

Author(s): Ahamadi M, Conrado DJ, Macha S, Sinha V, Stone J, Burton J, Nicholas T, Gallagher J, Dexter D, Bani M, Boroojerdi B, Smit H, Weidemann J, Chen C, Yang M, Maciuca R, Lawson R, Burn D, Marek K, Venuto C, Stafford B, Akalu M, Stephenson D, Romero K

Publication type: Article

Publication status: Published

Journal: Clinical Pharmacology and Therapeutics

Year: 2020

Volume: 107

Issue: 3

Pages: 553-562

Print publication date: 01/03/2020

Online publication date: 23/09/2019

Acceptance date: 05/09/2019

Date deposited: 07/10/2019

ISSN (print): 0009-9236

ISSN (electronic): 1532-6535

Publisher: Wiley


DOI: 10.1002/cpt.1634


Altmetrics provided by Altmetric