Highlights from

AAN 2019

American Academy of Neurology annual meeting

Philadelphia, USA 4-10 May 2019

Isradipine does not slow progression of disability in early Parkinson

In the phase 3 study STEADY-PD III, isradipine 10 mg daily failed to slow progression of disability in early Pakinson's Disease as measured by the Unified Parkinson Disease Rating Scale (UPDRS) total score medications in the ON state [1]. Still, the trial resulted in very valuable information and insights.

Isradipine is a dihydropyridine calcium channel antagonist that is approved for the treatment of hypertension. It was shown to be neuroprotective in in-vitro and in-vivo models of parkinsonism. The innovative trial design allowed for the determination of longer duration benefits on clinically relevant outcomes in a relatively small cohort on top of benefits from symptomatic therapy. The 336 participants from 54 Parkinson Study Group sites in USA and Canada were randomised to isradipine 10 mg daily or placebo for 3 years. The primary outcome measure was the change from baseline in the UPDRS Part I-III score measured in the ON state at month 36. Secondary outcomes included:

  • change in UPDRS-III in the OFF state;

  • time to initiation and utilisation of dopaminergic therapy;

  • time to onset of motor complications;

  • change in non-motor disability; and

  • quality of life measures.

Dr Tanya Simuni (Northwestern Medicine, USA) presented the results. She said the adjusted mean UPDRS I-III medications ON changes over 36 months were 2.99 points in the isradipine group and 3.26 points in the placebo group: a treatment effect of 0.27 points (P=0.85). Key secondary outcomes showed no statistically significant treatment effect. Isradipine was safe and well tolerated; the most notable side effect was edema.

“The study recruitment, retention, and compliance were excellent, with a retention rate of 95% in a 3 year study,” Dr Simuni told her audience. “I hope you agree that this study did not fail. It provided us with a lot of valuable information.” As to why isradipine failed, she speculated the dose may have been to low for this indication, the window of opportunity was perhaps already closed, or that the calcium channel may not be the leading cause of Pakinson's Disease. Secondary analysis is underway to explore biological and clinical correlates of disease progression.

  1. Simuni T, et al. A Phase 3 study of isradipine as a disease modifying agent in patients with early Parkinson's disease (STEADY-PD III): Final study results. AAN 2019, Plen02.001.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.