Efficacy of Isradipine in Early Parkinson Disease

Parkinson Disease Clinical Trial

Official title:

Phase 3 Double-blind Placebo-controlled Parallel Group Study of Isradipine as a Disease Modifying Agent in Subjects With Early Parkinson Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02168842
• Other study ID #: STEADY-PD III
• Secondary ID: U01NS080818-01A1
• Status: Completed
• Phase: Phase 3
• Start date: November 2014
• Est. completion date: November 2018

Study information

• Verified date: January 2020
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine whether treatment with isradipine is effective in slowing the progression of Parkinson disease disability.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 336
• Est. completion date: November 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Isradipine
Oral capsules Isradipine IR, up to 10 mg, taken twice daily
• Placebo (for Isradipine)
Sugar Pill manufactured to look like Isradipine but has no active ingredients

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Ottawa Hospital Civic Site	Ottawa	Ontario
Canada	Centre Hospitalier Affilie	Quebec City	Quebec
Canada	The Centre for Addiction and Mental Health	Toronto	Ontario
Canada	Toronto Western Hospital, University Health Network	Toronto	Ontario
United States	Albany Medical College	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston University Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Michigan State University	East Lansing	Michigan
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	The Parkinsons & Movement Disorder Institute	Fountain Valley	California
United States	Struthers Parkinson's Center	Golden Valley	Minnesota
United States	Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Pacific Health Research & Education Institute	Honolulu	Hawaii
United States	University of Texas Health Science Center	Houston	Texas
United States	University of California	Irvine	California
United States	Health Quest Kingston	Kingston	New York
United States	Booth Gardner Parkinson's Care Center	Kirkland	Washington
United States	University of Nevada School of Medicine	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Institute of Neurodegenerative Disorders	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	University of Rochester	Rochester	New York
United States	Washington University	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of California San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	LSU Health Science Center	Shreveport	Louisiana
United States	Atlantic Neuroscience Institute	Summit	New Jersey
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	University of South Florida	Tampa	Florida
United States	Sentara Neurology Specialists	Virginia Beach	Virginia

Sponsors (4)

Lead Sponsor	Collaborator
University of Rochester	Michael J. Fox Foundation for Parkinson's Research, National Institute of Neurological Disorders and Stroke (NINDS), The Parkinson Study Group

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adjusted Mean Change in UPDRS PIGD Score	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS PIGD Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS PIGD Score ranges from -1 to 3, larger value shows worsening of conditions.	Baseline to 36 months of treatment
Other	Adjusted Mean Change in UPDRS Tremor Score	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Tremor Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Tremor Score ranges from -1 to 2, larger value shows worsening of conditions.	Baseline to 36 months of treatment
Other	Adjusted Mean Change in H/Y Stage	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the H/Y Stage in the active treatment arm versus placebo between the baseline and 36 month visit. The change in H/Y Stage ranges from -1 to 3, larger value shows worsening of conditions.	Baseline to 36 months of treatment
Other	Adjusted Mean Change in Levodopa	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Levodopa in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED ranges from -200 to 2000, larger value shows more disability from PD.	Baseline to 36 months of treatment
Other	Adjusted Mean Change in Levodopa Cumulative	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Levodopa Cumulative in the active treatment arm versus placebo between the baseline and 36 month visit. The change of Levodopa cumulative ranges from 0 to 800000, larger value shows more disability from PD.	Baseline to 36 months of treatment
Other	Adjusted Mean Change in Systolic BP, Seated	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Systolic BP, Seated in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Systolic BP, Seated ranges from -65 to 50. larger value shows worsening of conditions.	Baseline to 36 months of treatment
Other	Adjusted Mean Change in Diastolic BP, Seated	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Diastolic BP, Seated in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Diastolic BP, Seated ranges from -35 to 25. larger value shows worsening of conditions.	Baseline to 36 months of treatment
Primary	Adjusted Mean Change in Total Unified Parkinson Disease Rating Scale (UPDRS) Score	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the total (Part I-III) UPDRS score in the active treatment arm versus placebo between the baseline and 36 month visit. The change of UPDRS ranges from -30 to 80, larger value shows more disability from PD.	Baseline to 36 months of treatment
Primary	Adjusted Mean Change in Adjusted UPDRS Score	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the adjusted UPDRS Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change of adjusted UPDRS ranges from -100 to 150, larger value shows more disability from PD.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in LED	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the LED(levodopa equivalent dose) in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED ranges from -100 to 3000, larger value shows more disability from PD.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in LED Cumulative	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the LED(levodopa equivalent dose) cumulative in the active treatment arm versus placebo between the baseline and 36 month visit. The change of LED cumulative ranges from 0 to 1200000, larger value shows more disability from PD.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in UPDRS Part IV	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part IV in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part IV ranges from -10 to 10, larger value shows more disability from PD.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in MDS-UPDRS nmEDL	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS nmEDL(Non-Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MDS-UPDRS nmEDL ranges from -6 to 10, larger value shows more disability from PD.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in MDS-UPDRS mEDL	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS mEDL(Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MDS-UPDRS mEDL ranges from -8 to 35, larger value shows more disability from PD.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in UPDRS Score to 1 Year	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MDS-UPDRS nmEDL(Non-Motor Experiences of Daily Living) in the active treatment arm versus placebo between the baseline and 12 month visit. The change of UPDRS ranges from -22 to 23, larger value shows more disability from PD.	Baseline to 12 months of treatment
Secondary	Adjusted Mean Change in UPDRS Part II	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part II (ADL Function) in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part II ranges from -12 to 19, larger value shows more disability from PD.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in UPDRS Part III OFF	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the UPDRS Part III OFF rating in the active treatment arm versus placebo between the baseline and 36 month visit. The change in UPDRS Part III OFF ranges from -30 to 100, larger value shows more disability from PD.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in SE/ADL	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the SE/ADL in the active treatment arm versus placebo between the baseline and 36 month visit. The change of UPDRS ranges from -70 to 20, larger value shows improvement of PD.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in Modified Rankin Score	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Modified Rankin Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Modified Rankin Score ranges from -1 to 3, larger value shows worsening of conditions.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in MoCA Score	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the MoCA Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in MoCA Score ranges from -10 to 6, larger value shows improvement of conditions.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in PDQ39 Total Score	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the PDQ39 Total Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in PDQ39 Total Score ranges from -16 to 44, larger value shows worsening of conditions.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in Ambulatory Capacity	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the Ambulatory Capacity in the active treatment arm versus placebo between the baseline and 36 month visit. The change in Ambulatory Capacity ranges from -4 to 12, larger value shows worsening of conditions.	Baseline to 36 months of treatment
Secondary	Adjusted Mean Change in BDI Total Score	Efficacy of isradipine to slow progression of Parkinson disease disability to be determined by the change in the BDI Total Score in the active treatment arm versus placebo between the baseline and 36 month visit. The change in BDI Total Score ranges from -9 to 22, larger value shows worsening of conditions.	Baseline to 36 months of treatment
Secondary	Risk of Need for Antiparkinsonian Therapy	Number of participants with need for Antiparkinsonian Therapy.	Baseline to 36 months of treatment
Secondary	Risk of Need for Dyskinesia	Number of participants with need for Dyskinesia Therapy.	Baseline to 36 months of treatment
Secondary	Risk of Need for Fluctuations	Number of participants with need for Fluctuations Therapy.	Baseline to 36 months of treatment

External Links

•   STEADY-PD III Study Website