Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease

NCT00909545 | Completed Phase 2 Results DMC

• 1 other identifier: CTCC Protocol #124
• Study Type: interventional
• Target: 99
• Locations: 2 countries
• Sites: 20

Brief 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.

Conditions

Parkinson Disease

Keywords

Early Parkinson disease

Outcome Measures

Primary Outcomes (1)

• Tolerability of the Three Dosages(5mg, 10mg and 20mg) of Isradipine CR.

  Tolerability will be judged by the proportion of subjects enrolled in a dosage group able to complete the 12 month study or to the time of initiation of dopaminergic therapy on their original assigned dosage. Tolerability of each active arm will be compared to placebo group.

  Baseline to 12 months or the time to require dopaminergic therapy

Secondary Outcomes (31)

• Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS)

  Baseline to 12 months or the time to require dopaminergic therapy

• Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale

  Baseline to 12 months or the time to require dopaminergic therapy

• Efficacy: Change in Activities of Daily Living(ADL) Subscale of the Unified Parkinson's Disease Rating Scale

  Baseline to 12 months or the time to require dopaminergic therapy

• Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale

  Baseline to 12 months or the time to require dopaminergic therapy

• Efficacy: Change in Modified Hoehn & Yahr Scale

  Baseline to 12 months or the time to require dopaminergic therapy

Study Arms (4)

Isradipine CR 5mg

ACTIVE COMPARATOR

Isradipine CR 5mg/day

Drug: Isradipine CR 5mg

Isradipine CR 10mg

ACTIVE COMPARATOR

Isradipine CR 10mg/day

Drug: Isradipine CR 10mg

Isradipine CR 20mg

ACTIVE COMPARATOR

Isradipine CR 20mg/day

Drug: Isradipine CR 20mg

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Isradipine CR 5mg DRUG

5mg dose: 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily

Also known as: Isradipine CR, Dynacirc CR

Isradipine CR 5mg

Isradipine CR 10mg DRUG

10mg dose: 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily

Also known as: Isradipine CR, Dynacirc CR

Isradipine CR 10mg

Isradipine CR 20mg DRUG

20mg dose: 4 Dynacirc CR 5mg tablets once daily

Also known as: Isradipine CR, Dynacirc CR

Isradipine CR 20mg

Placebo DRUG

4 Placebo to Match (PTM) tablets once daily

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator
• Northwestern University Dixon Fund: collaborator
• The Parkinson Study Group: collaborator

Study Sites (20)

Parkinson Institute

Sunnyvale, California, 94805, United States

Location

Institute for Neurodegenerative Disorders

New Haven, Connecticut, 06510, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of South Flordia

Tampa, Florida, 33606, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

Pacific Health Institute

Honolulu, Hawaii, 96817, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Park Nicolet Clinic

Golden Valley, Minnesota, 55427, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Rochester

Rochester, New York, 14618, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Tennessee

Memphis, Tennessee, 38104, United States

Location

Ottowa Hospital Civic Site

Ottawa, Ontario, K1Y 4E9, Canada

Location

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

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MeSH Terms

Conditions

Parkinson Disease

Interventions

Isradipine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Tanya Simuni, MD
• Organization: Feinberg School of Medicine, Northwestern University

TSimuni@nmff.org

312-503-2970

Study Officials

• Tanya Simuni, MS

  Northwestern University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicpal Investigator

Study Record Dates

• First Submitted: May 26, 2009
• First Posted: May 28, 2009
• Study Start: July 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: February 1, 2012
• Last Updated: April 17, 2013
• Results First Posted: April 17, 2013

Record last verified: 2013-04

Locations

US (18); CA (2)