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A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY-PD III).

ABSTRACT: To describe the rationale for a novel study design and baseline characteristics of a disease-modifying trial of isradipine 10 mg daily in early Parkinson disease (PD).STEADY-PDIII is a 36-month, Phase 3, parallel group, placebo-controlled study of the efficacy of isradipine 10 mg 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 nonmotor disability. Exploratory measures include global measures of functional disability, quality of life, change in the ambulatory capacity, cognitive function, and pharmacokinetic analysis. Rationale for the current design and alternative design approaches are discussed.The entire cohort of 336 participants was enrolled at 55 Parkinson Study Group sites in North America. The percentage of male participants were 68.5% with a mean age of 61.9 years (sd 9.0), mean Hoehn and Yahr stage of 1.7 (sd 0.5), mean UPDRS total of 23.1 (sd 8.6), and MoCA of 28.1 (sd 1.4).STEADY-PD III has a novel and innovative design allowing for the determination of longer duration benefits on clinically relevant outcomes in a relatively small cohort on top of the benefit derived from symptomatic therapy. Baseline characteristics are similar to those in previously enrolled de novo PD trials. 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.

SUBMITTER: Biglan KM

PROVIDER: S-EPMC5454402 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY-PD III).

Biglan Kevin M KM Oakes David D Lang Anthony E AE Hauser Robert A RA Hodgeman Karen K Greco Brittany B Lowell Jillian J Rockhill Rebecca R Shoulson Ira I Venuto Charles C Young Diony D Simuni Tanya T

Annals of clinical and translational neurology 20170509 6

<h4>Objective</h4>To describe the rationale for a novel study design and baseline characteristics of a disease-modifying trial of isradipine 10 mg daily in early Parkinson disease (PD).<h4>Methods</h4>STEADY-PDIII is a 36-month, Phase 3, parallel group, placebo-controlled study of the efficacy of isradipine 10 mg 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. <i>Secondar ...[more]

PMID: 28589163

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Project description:BackgroundStudies suggest that dihydropyridine calcium-channel blockers may be associated with reduced risk for Parkinson disease (PD).ObjectiveTo assess the effect of isradipine, a dihydropyridine calcium-channel blocker, on the rate of clinical progression of PD.DesignMulticenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT02168842).Setting57 Parkinson Study Group sites in North America.ParticipantsPatients with early-stage PD (duration <3 years) who were not taking dopaminergic medications at enrollment.Intervention5 mg of immediate-release isradipine twice daily or placebo for 36 months.MeasurementsThe primary outcome was change in the Unified Parkinson's Disease Rating Scale (UPDRS) parts I to III score measured in the antiparkinson medication "ON" state between baseline and 36 months. Secondary outcomes included time to initiation and use of antiparkinson medications, time to onset of motor complications, change in nonmotor disability, and quality-of-life measures.Results336 patients were randomly assigned (mean age, 62 years [SD, 9]; 68% men; disease duration, 0.9 year [SD, 0.7]; mean UPDRS part I to III score, 23.1 [SD, 8.6]); 95% of patients completed the study. Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85). Statistical adjustment for antiparkinson medication use did not change the findings. Secondary outcomes showed no effect of isradipine treatment. The most common adverse effects of isradipine were edema and dizziness.LimitationThe isradipine dose may have been insufficient to engage the target calcium channels associated with neuroprotective effects.ConclusionLong-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.Primary funding sourceNational Institute of Neurological Disorders and Stroke.

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A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY-PD III).

Publications

A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY-PD III).

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