Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Intervention: Isradipine CR 5mg; Isradipine CR 10mg; Isradipine CR 20mg; Placebo
Intervention description: 5mg dose: 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily; 10mg dose: 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily; 20mg dose: 4 Dynacirc CR 5mg tablets once daily; 4 Placebo to Match (PTM) tablets once daily
Intervention MeSH terms: Isradipine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 99.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: Early Parkinson disease

Summary:

      The primary purpose of this study is to establish a dosage of isradipine CR that is tolerable
      and demonstrates preliminary efficacy for utilization in future pivotal efficacy studies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with early idiopathic PD. If tremor is not present, subjects must have
             unilateral onset and persistent asymmetry of the symptoms.

          -  Be over 30 years old at the time of diagnosis of PD.

          -  Hoehn & Yahr stage is less than or equal to 2.5.

          -  Currently not receiving dopaminergic therapy and not projected to require dopaminergic
             therapy for at least 6 months from enrollment.

          -  Use of MAO-B inhibitors (rasagiline, selegiline), amantadine, or anticholinergics will
             be allowed. The dosage has to be stable for 3 months prior to baseline visit and
             throughout the duration of the study.

        Exclusion Criteria:

          -  Subjects with a diagnosis of an atypical Parkinsonism

          -  Subjects unwilling or unable to give informed consent

          -  Use of CoQ10 at a dosage >600mg daily or use of creatine >5 grams daily within the 60
             days prior to randomization

          -  Exposure to dopaminergic PD therapy within 60 days prior to enrollment or for 3 months
             or more at any point in the past

          -  History of clinically significant orthostatic hypotension or presence of orthostatic
             hypotension at the screening visit defined as > 20 mmHg change in systolic BP and
             >10mm change in diastolic BP after 2 min of standing, or baseline BP <90/60

          -  History of congestive heart failure

          -  History of bradycardia defined as heart rate <55

          -  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
             electrocardiogram.

          -  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 calcium channel blockers within 6 months of
             baseline

          -  Subjects with history of hypertension treated with a maximum of 2 other
             antihypertensive agents will be allowed provided that the doses 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 physician or cardiologist.

          -  Use of grapefruit juice, Ginkgo biloba, St. John's wart and/or ginseng will be
             prohibited during the study (as they interfere with the metabolism of isradipine).

          -  Presence of cognitive dysfunction defined by a Mini Mental Status Exam ( MMSE) score <
             26 at screening

          -  Subjects with clinically significant depression as determined by a Beck Depression
             Inventory (BDI) score >15 at screening

          -  History of exposure to typical or atypical antipsychotics or other dopamine blocking
             agents within 6 months prior to enrollment

          -  Subjects have to be on a stable regimen of central nervous system acting medications
             (benzodiazepines, antidepressants, hypnotics) for 30 days prior to enrollment

          -  Lactating women or women of childbearing potential who are not surgically sterilized
             have to use a reliable measure of contraception and have a negative serum pregnancy
             test at screening

          -  Participation in other investigational drug trials within 30 days prior to screening

          -  History of brain surgery for PD