STEADY-PD III

PD is the second most common neurodegenerative disease that affects 1% of the population above the age 65. The principal motor symptoms of PD are attributable to the preferential loss of dopaminergic neurons in the substantia nigra pars compacta. Recent data demonstrated that the selective vulnerability of these neurons may be due to the reliance of these and other neurons susceptible to PD pathology, on L-type Cav1.3 Ca2+ channels and, more importantly for PD, that blocking these channels with israpadine, a dihydropyridine Ca2+ channel antagonist, protects these neurons in in vitro and in vivo models of parkinsonism. Recent epidemiological data also points to a reduced risk of PD with chronic use of dihydropyridines. Isradipine is an approved agent for the treatment of hypertension. Phase II clinical studies found that isradipine is safe and tolerable at the daily dose of 10 mg or below in participants with early PD. Isradipine penetrates the blood brain barrier and 10 mg daily dose is expected to achieve serum concentrations within the range found to be neuroprotective in animal models of PD.

Based on these results, STEADY-PD3 was conducted as a randomized Phase 3, 2-arm, double-blind, parallel group trial with subjects randomized to Isradipine immediate release 5 mg or matching placebo twice daily for 36 months. The primary efficacy measure was the change in the total UPDRS score in the active treatment arm versus placebo between the baseline and 36 months. If patients needed to start symptomatic therapy, they continued on their randomized treatment assignment in conjunction with the symptomatic therapy and primary outcome was assessed in the medications ON state. The primary analysis was based on the intent-to-treat principle and included all subjects who had 36 month data. The study had 95 % retention rate. 

The study was negative for the primary outcome, showing no difference in PD symptoms over the 3 years of the study between the active and placebo arms.