Efficacy of Isradipine in Early Parkinson Disease
Efficacy of Isradipine in Early Parkinson Disease
The purpose of the study is to determine whether treatment with isradipine is effective in
 slowing the progression of Parkinson disease disability.
The study will enroll 336 participants in this multi-center study at approximately 56 sites
 across the US and Canada. In this study, we are comparing 10 mg of Isradipine to Placebo for
 treatment of newly diagnosed PD patients. Isradipine has been approved by the Food and Drug
 Administration (FDA) to treat high blood pressure but is considered investigational in this
 study, as it has not been approved for use in patients with PD.Isradipine can affect the
 function of specialized channels that are present in the types of brain cells that are
 affected in PD patient. These cells are usually responsible for making dopamine, which is
 depleted in patients with PD. Isradipine may block the damage caused by the flow of certain
 chemicals through these channels. Laboratory data has showed that Isradipine may prevent the
 development of Parkinson-like symptoms in animal studies. Isradipine has been evaluated in
 some patients with PD. The first study with isradipine controlled release (CR) in patients
 with early PD and normal blood pressure found that the drug was reasonably well tolerated and
 safe. The controlled release formulation of isradipine is not available for use and therefore
 this study is using the immediate release formulation. Eligible participants will be followed
 for up to 36 months and will be expected to complete 12 in-person visits and 4 telephone
 visits. The study visits will include clinical assessment of motor, neuropsychiatric and
 cognitive testing as well as collection of blood and urine samples. Study drug will taken
 twice daily, in the morning and in the evening with or without food. Prior to taking study
 drug, study participants will be required to take their blood pressure with a home blood
 pressure device provided to them for use in this study.
Inclusion Criteria:

 -  Subjects with early idiopathic PD (presence of at least two out of three cardinal
 manifestations of PD). If tremor is not present, subjects must have unilateral onset
 and persistent asymmetry of the symptoms

 -  Age equal or greater than 30 years at the time of diagnosis of PD

 -  Hoehn and Yahr stage less than or equal to 2

 -  Diagnosis of PD less than 3 years.

 -  Currently NOT receiving dopaminergic therapy (levodopa, dopamine agonist or MAO-B
 inhibitors) and NOT projected to require PD symptomatic therapy for at least 3 months
 from the baseline visit

 -  Use of amantadine and/or anticholinergics will be allowed provided that the dose is
 stable for 8 weeks prior to the baseline visit

 -  If subject is taking any central nervous system acting medications (e.g.,
 benzodiazepines, antidepressants, hypnotics) regimen must be stable for 30 days prior
 to the baseline visit

 -  Women of childbearing potential may enroll but must use a reliable measure of
 contraception and have a negative serum pregnancy test at the screening visit

 Exclusion Criteria:

 -  Subjects with a diagnosis of an atypical Parkinsonism

 -  Subjects unwilling or unable to give informed consent

 -  Exposure to dopaminergic PD therapy within 60 days prior to baseline visit or for
 consecutive 3 months or more at any point in the past

 -  History of clinically significant orthostatic hypotension or presence of orthostatic
 hypotension at the screening or baseline visit defined as greater than or equal to 20
 mmHg change in systolic BP and greater than or equal to 10 mmHg change in diastolic BP
 from sitting position to standing after 2 minutes, or baseline sitting BP less than
 90/60

 -  History of congestive heart failure

 -  Clinically significant bradycardia

 -  Presence of 2nd or 3rd degree atrioventricular block or other significant ECG
 abnormalities that in the investigator's opinion would compromise participation in
 study

 -  Clinically significant abnormalities in the Screening Visit laboratory studies or ECG

 -  Presence of other known medical or psychiatric comorbidity that in the investigator's
 opinion would compromise participation in the study

 -  Prior exposure to isradipine or other dihydropyridine calcium channel blockers within
 6 months of the baseline visit

 -  Subjects on greater than 2 concomitant antihypertensive medications. If a history of
 hypertension, then a maximum of 2 other antihypertensive agents will be allowed
 provided that the dosages of concomitant anti HTN therapy can be reduced/adjusted
 during the study based on the BP readings in consultation with the subject's primary
 care provider or cardiologist. Use of any concomitant calcium channel blockers will
 not be allowed from the baseline visit and for the duration of the study

 -  Use of grapefruit juice, ginkgo biloba, St. John's wort or ginseng will be prohibited
 starting from the screening visit and for the duration of the study (as they interfere
 with the metabolism of isradipine)

 -  Use of clarithromycin, telithromycin and erythromycin will be prohibited starting from
 the screening visit and for the duration of the study as the combination of
 clarithromycin, telithromycin or erythromycin and calcium channel blockers has been
 reported to be associated with increased risk of kidney and heart injury

 -  Presence of cognitive dysfunction defined by a Montreal Cognitive assessment (MoCA)
 score of less than 26 at screening

 -  Subjects with clinically significant depression as determined by a Beck Depression
 Inventory II (BDI) score greater than 15 at the screening visit

 -  History of exposure to typical or atypical antipsychotics or other dopamine blocking
 agents within 6 months prior to the baseline visit

 -  History of use of an investigational drug within 30 days prior to the screening visit

 -  History of brain surgery for PD

 -  Allergy/sensitivity to isradipine or its matching placebo or their formulations

 -  Pregnant or lactating woman