Objective: To evaluate the efficacy of isradipine 10 mg daily to slow progression of disability in early PD.

Background: Isradipine, a dihydropyridine calcium channel antagonist, is neuroprotective in in vitro/in vivo models of parkinsonism. Epidemiological data suggests a reduced risk of PD with chronic use of dihydropyridines.  Our Phase II study found isradipine 10 mg daily to be safe and well tolerated in early Parkinson’s disease (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 10mg daily in 336 participants with early PD as measured by the change in the Unified Parkinson Disease Rating Scale (UPDRS) Part I-III score in the practically defined ON state. Secondary outcome measures include clinically meaningful measures of disability progression in early PD: 1) Time to initiation and utilization of dopaminergic therapy; 2) Time to onset of motor complications; 3) Change in non-motor disability. Exploratory measures include global measures of functional disability, quality of life, change in the ambulatory capacity, cognitive function and pharmacokinetic analysis. In addition, DNA and plasma were collected at screening for future unspecified research.

Results: The study was funded by NINDS and MJFF and is being conducted at 54 Parkinson Study Group sites in US and Canada.  Recruitment was completed in 12 months, 6 months ahead of the schedule. A total of 336 subjects have been enrolled. The cohort is 68.5% male (n=230) and 10.7% (n=36) are ethnic and racial minorities. At baseline, the mean (SD) age is 61.9 (9.0) years; the total UPDRS is 23.1 (8.6); and the MOCA is 28.1 (1.4). There have been 6 premature withdrawals (4.8%), 32 Serious Adverse Events (all unrelated to study drug) including 1 death. Greater than two thirds (n=230) have initiated symptomatic therapy. The last subject is anticipated to complete the study in November 2018.   

Conclusions: STEADY-PD III is fully enrolled and the population is similar to other early PD clinical trial cohorts. Retention has been excellent at this point. 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.  

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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-parkinsons-disease-steady-pd-iii-baseline-characteristics-and-study-update/