Objective: To evaluate the efficacy of isradipine 10 mg daily on Parkinson disease (PD) disability.

Background: Isradipine, a dihydropyridine calcium channel antagonist with excellent penetration of the blood brain barrier, has been shown to be neuroprotective in in vitro /in vivo models of parkinsonism. Epidemiological data also points to a reduced risk of PD with chronic use of dihydropyridines. Our recently completed Phase II study found that isradipine 10 mg daily is safe and well tolerated in participants with early PD; a dosage that achieves serum concentrations found to be neuroprotective in animal models of PD.

Methods: The study is a 36-month, Phase 3, parallel group, placebo-controlled study of the efficacy of isradipine 10 mg daily on the progression of PD disability in 336 participants with early PD as measured by the change in the Unified Parkinson Disease Rating Scale(UPDRS) Part I-III score. Secondary outcome measures include a number of clinically meaningful and widely accepted measures of progression of disability in early PD including: 1)Time to initiation and utilization of dopaminergic therapy; 2)Time to onset of motor complications; 3)Change in non-motor disability. Exploratory measures will include global measures of functional disability, quality of life, change in the ambulatory capacity (sum of 5 baseline values UPDRS items: falling, freezing, walking, gait, postural stability), cognitive function and pharmacokinetic analysis.

Results: The study was funded by NINDS and is being conducted at 54 Parkinson Study Group sites in US and Canada.The study completed enrollment of 336 participants on October 28, 2015 and maintains 96% retention rate. As of March 8, 2018 of 336, 76 participants have completed the study, 247 are active, 237 on study drug.The cohort is 68.5% male and 90.1% white non-hispanic. At baseline the mean(SD) age was 61.9(9.03) years; total UPDRS was 23.10 (8.6); and the MOCA was 28.09(1.35). There have been 13 premature withdrawals, 61 serious adverse events including 2 deaths(deemed unrelated to study drug).The last participant is anticipated to complete the study in November 2018.

Conclusions: STEADY-PD III is fully enrolled and maintains high retention rate.This study represents a unique opportunity to evaluate the potential impact of a novel therapy to slow progression of PD disability and provide clinically meaningful benefits. The study results are expected in early 2019.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-phase-3-study-of-isradipine-as-a-disease-modifying-agent-in-patients-with-early-parkinson-diseasesteady-pd-iii-baseline-characteristics-and-study-update/