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Phase II safety, tolerability, and dose selection study of isradipine as a potential disease-modifying intervention in early Parkinson's disease (STEADY-PD)

Authors

  • Parkinson Study Group

    Corresponding author
    1. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, USA
    • Correspondence to: Dr. Tanya Simuni, Department of Neurology, Northwestern University Feinberg School of Medicine, 710 North Lake Shore Drive, 1126, Chicago, IL 60611, USA; tsimuni@nmff.org

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  • Funding agencies: Michael J. Fox Foundation (MJFF); Northwestern Memorial Foundation Dixon Priority award.

  • Relevant conflicts of interest/financial disclosures: J.D. Surmeier has a pending use patent for the use of dihydropyridine compounds in Parkinson's disease. The rest of the authors have nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

  • Members of the Parkinson Study Group are listed in the Appendix.

ABSTRACT

Isradipine, a dihydropyridine calcium channel antagonist, has been shown to be neuroprotective in animal models of Parkinson's disease (PD). To establish a dosage of isradipine controlled-release (CR) that is tolerable and demonstrates preliminary efficacy for use in a future pivotal efficacy trial a Phase 2, randomized, double-blind, parallel group trial (Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease [STEADY-PD]) was undertaken in subjects with early PD not requiring dopaminergic therapy (dopamine agonists or levodopa) randomized 1:1:1:1 to 5, 10, or 20 mg of isradipine CR or matching placebo daily. The primary outcome was tolerability defined as no more than a 30% difference in the proportion of patients completing the study on the originally assigned dosage between an active and placebo group. If more than one isradipine dosage was tolerable, then a 3-point difference in total Unified Parkinson's Disease Rating Scale (UPDRS) change between baseline and week 52 (or time to sufficient disability to require dopaminergic therapy) was taken as a criterion for selection of the most desirable dosage for future study. STEADY-PD enrolled 99 subjects. The tolerability of isradipine was dose dependent: placebo, 25 of 26 patients (96%); 5 mg, 19 of 23 patients (83%); 10 mg 19 of 26 patients (73%); and 20 mg 9 of 24 patients (37%). There was no difference in change in UPDRS among dosages. The most common adverse events were peripheral edema (30) and dizziness (24). Isradipine 10 mg daily was the maximal tolerable dosage in this study of early PD. A large placebo-controlled trial will be necessary and is planned to assess efficacy of isradipine 10 mg daily to slow progression of PD disability. © 2013 International Parkinson and Movement Disorder Society.

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