Parkinson Disease
Conditions
Keywords
Early Parkinson disease
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.
Detailed description
There is solid scientific rational and preclinical data supporting a clinical trial of isradipine CR as a potential disease modifying agent in early PD. Human pharmacokinetic data demonstrate that it is feasible to achieve the serum concentrations in humans that were neuroprotective in preclinical models with the FDA approved dosage range. Pilot data demonstrate acceptable tolerability of isradipine CR in the PD population. Tolerability is inversely proportional to the dosage dependent. Considering that tolerability of isradipine CR is inversely proportional to the dosage exposure, it is essential to proceed with the dose selection tolerability study in preparation for the future efficacy trials. The tolerability, defined as the ability to complete the study, of three dosages of isradipine CR relative to placebo in subjects with early Parkinson's disease will be examined first. The dosage that is tolerable and demonstrates preliminary efficacy will be evaluated further in the future pivotal efficacy studies.
Interventions
DRUGIsradipine CR 5mg
5mg dose: 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily
DRUGIsradipine CR 10mg
10mg dose: 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily
DRUGIsradipine CR 20mg
20mg dose: 4 Dynacirc CR 5mg tablets once daily
DRUGPlacebo
4 Placebo to Match (PTM) tablets once daily
Sponsors
Michael J. Fox Foundation for Parkinson's Research
Northwestern University Dixon Fund
The Parkinson Study Group
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of the Three Dosages(5mg, 10mg and 20mg) of Isradipine CR. | Baseline to 12 months or the time to require dopaminergic therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale | Baseline to 12 months or the time to require dopaminergic therapy | The outcome is defined as change in Mental subscale of Unified Parkinson's Disease Rating Scale(UPDRS Part I) between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. UPDRS Part I: Mentation, behavior and mood, consisting of 4 questions answered on a 0-4 point scale where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Total score represents the sum of these 4 questions. A greater increase in score indicates a greater increase in disability. A total of 16 points are possible. 16 represents the worst (total) disability), 0--no disability. |
| 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 | The outcome is defined as change in ADL subscale of the Unified Parkinson's Disease Rating Scale(UPDRS Part II) between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. UPDRS Part II: Activities of Daily Living in the week prior to the designated visit, consisting of 13 questions answered on a 0-4 point scale where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Total Part II score represents the sum of these 13 questions. A greater increase in score indicates a greater increase in disability. A total of 52 points are possible. 52 represents the worst (total) disability), 0--no disability |
| Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale | Baseline to 12 months or the time to require dopaminergic therapy | The outcome is defined as change in Motor subscale of the Unified Parkinson's Disease Rating Scale(UPDRS Part III) between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. UPDRS Part III: motor abilities at the time of the visit, consisting of 27 items (including 13 general questions and 14 sub-questions) each answered on a 0-4 point scale where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Total Part III score represents the sum of these 27 items. A total of 108 points are possible. 108 represents the worst (total) disability), 0--no disability. |
| Efficacy: Change in Modified Hoehn & Yahr Scale | Baseline to 12 months or the time to require dopaminergic therapy | The Modified Hoehn & Yahr Scale is an 8-level Parkinson's disease staging instrument. The outcome is defined as change in Modified Hoehn & Yahr Scale between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. A greater increase in stage indicates a greater increase in disability. Stage ranges from 0-5 (also including 1.5 and 2.5) with 0 indicating no disability and 5 indicating maximum disability. |
| Efficacy: Change in Modified Schwab & England Independence Scale | Baseline to 12 months or the time to require dopaminergic therapy | The Schwab & England scale is an investigator and subject assessment of the subject's level of independence at all scheduled study visits. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson's disease appeared. The outcome is defined as change in Schwab & England Independence Scale between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. Higher decrease in score indicates higher disability. Score ranges from 100% (complete independence) to 0% (total disability). |
| Efficacy: Change in Beck Depression Inventory II (BDI-II) | Baseline to 12 months or the time to require dopaminergic therapy | The Beck Depression Inventory (BDI) is a validated self-reported 21-item depression scale that was tested and validated as a reliable instrument for screening for depression in PD. The outcome is defined as change in BDI-II between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. Total BDI score represents the sum of these 21-items. A higher change in score indicates a greater increase in disability. Total score of 0-13 is considered minimal, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. |
| Efficacy: Change in Montreal Cognitive Assessment | Baseline to 12 months or the time to require dopaminergic therapy | The Montreal Cognitive Assessment(MoCA) is a brief 30-point screening instrument that was developed and validated to identify subjects with mild cognitive impairment. The outcome is defined as change in MoCA between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. Total MoCA score represents the sum of these 30-points, with a lower score indicating greater cognitive impairment. 30 is the maximum score, with a score of 26 or higher considered normal and below 26 indicative of Mild Cognitive Impairment. |
| Efficacy: Change in Parkinson Disease Quality of Life Questionnaire-39(PDQ-39) | Baseline to 12 months or the time to require dopaminergic therapy | The PD Quality of Life Scale(PDQ-39) asks the subject to evaluate how Parkinson disease has affected their health and overall quality of life at that point in time. The total quality of life scale includes subscales relating to social role, self-image/sexuality, sleep, outlook, physical function and urinary function. The outcome is defined as change in PDQ-39 between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. It is scored on a scale of zero to 100, with lower scores indicating better health and higher scores more severe disability. |
| Vital Signs: Change in Systolic Standing | Baseline to 12 months or the time to require dopaminergic therapy | — |
| Vital Signs: Change in Systolic Supine | Baseline to 12 months or the time to require dopaminergic therapy | — |
| Vital Signs: Change in Diastolic Standing | Baseline to 12 months or the time to require dopaminergic therapy | — |
| Vital Signs: Change in Diastolic Supine | Baseline to 12 months or the time to require dopaminergic therapy | — |
| Vital Signs: Change in Pulse Standing | Baseline to 12 months or the time to require dopaminergic therapy | — |
| Vital Signs: Change in Pulse Supine | Baseline to 12 months or the time to require dopaminergic therapy | — |
| Common Adverse Events: Oedema Peripheral | Baseline to 12 months or the time to require dopaminergic therapy | General disorders and administration site conditions. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. |
| Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS) | Baseline to 12 months or the time to require dopaminergic therapy | Outcome is defined as change in total Unified Parkinson's Disease Rating Scale (UPDRS) between the baseline visit and month 12 or the time to require dopaminergic therapy (last visit before subject goes on dopaminergic therapy), whichever occurs first. The UPDRS score has 4 components. Part I assesses mentation; Part II assesses activities of daily living; Part III assesses motor abilities; Part IV assesses complications of therapy. A total of 44 items are included in Parts I-III. Each item will receive a score ranging from 0 to 4 where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Part IV contains 11 items, 4 of these items are scored 0-4 in the same manner, and 7 are scored 0-1, with 0 indicating the absence of impairment and 1 indicating the presence of impairment. Total UPDRS score represents the sum of these items in Parts I-IV. A total of 199 points are possible. 199 represents the worst (total) disability), 0--no disability. |
| Common Adverse Events: Nasopharyngitis | Baseline to 12 months or the time to require dopaminergic therapy | Infections and infestations. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Headache | Baseline to 12 months or the time to require dopaminergic therapy | Nervous System disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Constipation | Baseline to 12 months or the time to require dopaminergic therapy | Gastrointestinal Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Fatigue | Baseline to 12 months or the time to require dopaminergic therapy | General Disorders and Administration Site Conditions. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Nausea | Baseline to 12 months or the time to require dopaminergic therapy | Gastrointestinal Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Upper Respiratory Tract Infection | Baseline to 12 months or the time to require dopaminergic therapy | Infections and Infestations. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Depression | Baseline to 12 months or the time to require dopaminergic therapy | Psychiatric Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Somnolence | Baseline to 12 months or the time to require dopaminergic therapy | Nervous System Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Insomnia | Baseline to 12 months or the time to require dopaminergic therapy | Psychiatric Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Dyspepsia | Baseline to 12 months or the time to require dopaminergic therapy | Gastrointestinal Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Diarrhoea | Baseline to 12 months or the time to require dopaminergic therapy | Gastrointestinal Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Sinusitis | Baseline to 12 months or the time to require dopaminergic therapy | Infections and Infestations. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Back Pain | Baseline to 12 months or the time to require dopaminergic therapy | Musculoskeletal and Connective Tissue Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Hypotension | Baseline to 12 months or the time to require dopaminergic therapy | Vascular Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
| Common Adverse Events: Dizziness | Baseline to 12 months or the time to require dopaminergic therapy | Nervous system disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 4 Placebo to Match (PTM) tablets once daily | 26 |
| Isradipine CR 5mg/Day 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily | 23 |
| Isradipine CR 10mg/Day 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily | 26 |
| Isradipine CR 20mg/Day 4 Dynacirc CR 5mg tablets once daily | 24 |
| Total | 99 |
Baseline characteristics
| Characteristic | Isradipine CR 5mg/Day | Total | Isradipine CR 20mg/Day | Placebo | Isradipine CR 10mg/Day |
|---|---|---|---|---|---|
| Age Continuous | 57.7 years STANDARD_DEVIATION 8.3 | 59.1 years STANDARD_DEVIATION 9.8 | 59.8 years STANDARD_DEVIATION 8.9 | 60.2 years STANDARD_DEVIATION 10.1 | 58.5 years STANDARD_DEVIATION 11.6 |
| Age, Customized >=65 years | 5 participants | 27 participants | 5 participants | 9 participants | 8 participants |
| Age, Customized Between 30 and 65 years | 18 participants | 72 participants | 19 participants | 17 participants | 18 participants |
| Hoehn & Yahr Scale H/Y Stage: 1 | 4 Participants | 30 Participants | 11 Participants | 7 Participants | 8 Participants |
| Hoehn & Yahr Scale H/Y Stage: 1.5 | 3 Participants | 6 Participants | 1 Participants | 2 Participants | 0 Participants |
| Hoehn & Yahr Scale H/Y Stage: 2 | 16 Participants | 61 Participants | 11 Participants | 16 Participants | 18 Participants |
| Hoehn & Yahr Scale H/Y Stage: 2.5 | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Modified Schwab & England Independence Scale | 93.48 Percentage scale STANDARD_DEVIATION 4.632 | 92.0 Percentage scale STANDARD_DEVIATION 5 | 91.04 Percentage scale STANDARD_DEVIATION 5.1 | 93.08 Percentage scale STANDARD_DEVIATION 5.11 | 93.08 Percentage scale STANDARD_DEVIATION 5.11 |
| Montreal Cognitive Assessment | 27.96 Unit of MoCA STANDARD_DEVIATION 1.97 | 27.4 Unit of MoCA STANDARD_DEVIATION 2.2 | 27.79 Unit of MoCA STANDARD_DEVIATION 1.89 | 26.96 Unit of MoCA STANDARD_DEVIATION 2.58 | 26.92 Unit of MoCA STANDARD_DEVIATION 2.36 |
| PD Qualify of Life Scale | 9.69 Unit of PDQ-39 STANDARD_DEVIATION 6.88 | 9.7 Unit of PDQ-39 STANDARD_DEVIATION 2.3 | 10.45 Unit of PDQ-39 STANDARD_DEVIATION 8.06 | 10.28 Unit of PDQ-39 STANDARD_DEVIATION 8.55 | 8.39 Unit of PDQ-39 STANDARD_DEVIATION 5.82 |
| Race/Ethnicity, Customized Other race | 1 participants | 8 participants | 2 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized White | 22 participants | 91 participants | 22 participants | 25 participants | 22 participants |
| Region of Enrollment Canada | 2 participants | 9 participants | 3 participants | 2 participants | 2 participants |
| Region of Enrollment United States | 21 participants | 90 participants | 21 participants | 24 participants | 24 participants |
| Sex: Female, Male Female | 8 Participants | 30 Participants | 8 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 15 Participants | 69 Participants | 16 Participants | 21 Participants | 17 Participants |
| Unified Parkinson's Disease Rating Scale (UPDRS) Activities of Daily Living (ADL) | 5.83 Unit of UPDRS scales STANDARD_DEVIATION 3.02 | 6.1 Unit of UPDRS scales STANDARD_DEVIATION 3 | 6.58 Unit of UPDRS scales STANDARD_DEVIATION 3.03 | 5.85 Unit of UPDRS scales STANDARD_DEVIATION 2.98 | 6.15 Unit of UPDRS scales STANDARD_DEVIATION 3.03 |
| Unified Parkinson's Disease Rating Scale (UPDRS) Mental | 1.30 Unit of UPDRS scales STANDARD_DEVIATION 1.79 | 0.9 Unit of UPDRS scales STANDARD_DEVIATION 1.3 | 0.96 Unit of UPDRS scales STANDARD_DEVIATION 1.12 | 0.65 Unit of UPDRS scales STANDARD_DEVIATION 1.06 | 0.65 Unit of UPDRS scales STANDARD_DEVIATION 0.98 |
| Unified Parkinson's Disease Rating Scale (UPDRS) Motor | 19.30 Unit of UPDRS scales STANDARD_DEVIATION 8.02 | 18.0 Unit of UPDRS scales STANDARD_DEVIATION 7.8 | 17.13 Unit of UPDRS scales STANDARD_DEVIATION 8.26 | 18.96 Unit of UPDRS scales STANDARD_DEVIATION 7.27 | 16.85 Unit of UPDRS scales STANDARD_DEVIATION 7.88 |
| Unified Parkinson's Disease Rating Scale (UPDRS) Total | 26.43 Unit of UPDRS scales STANDARD_DEVIATION 9.69 | 25.0 Unit of UPDRS scales STANDARD_DEVIATION 9.9 | 24.67 Unit of UPDRS scales STANDARD_DEVIATION 10.77 | 25.46 Unit of UPDRS scales STANDARD_DEVIATION 9.39 | 23.65 Unit of UPDRS scales STANDARD_DEVIATION 9.97 |
| Vital Signs: Diastolic Standing | 84.43 mm Hg STANDARD_DEVIATION 12.22 | 82.3 mm Hg STANDARD_DEVIATION 11.4 | 81.29 mm Hg STANDARD_DEVIATION 11.02 | 83.73 mm Hg STANDARD_DEVIATION 12.74 | 80.04 mm Hg STANDARD_DEVIATION 9.73 |
| Vital Signs: Diastolic Supine | 79.22 mm Hg STANDARD_DEVIATION 9.5 | 79.1 mm Hg STANDARD_DEVIATION 10.5 | 79.63 mm Hg STANDARD_DEVIATION 10.43 | 80.69 mm Hg STANDARD_DEVIATION 11.34 | 76.88 mm Hg STANDARD_DEVIATION 10.95 |
| Vital Signs: Pulse Standing | 77.35 Beats per minute STANDARD_DEVIATION 10.7 | 74.5 Beats per minute STANDARD_DEVIATION 11.6 | 72.33 Beats per minute STANDARD_DEVIATION 11.43 | 72.92 Beats per minute STANDARD_DEVIATION 11.9 | 75.50 Beats per minute STANDARD_DEVIATION 12.27 |
| Vital Signs: Pulse Supine | 67.43 Beats per minute STANDARD_DEVIATION 10.28 | 67.2 Beats per minute STANDARD_DEVIATION 9.6 | 66.33 Beats per minute STANDARD_DEVIATION 9.71 | 68.00 Beats per minute STANDARD_DEVIATION 10.63 | 67.08 Beats per minute STANDARD_DEVIATION 8.39 |
| Vital Signs: Systolic Standing | 127.3 mm Hg STANDARD_DEVIATION 17.03 | 128.4 mm Hg STANDARD_DEVIATION 16.3 | 125.8 mm Hg STANDARD_DEVIATION 11.96 | 130.0 mm Hg STANDARD_DEVIATION 18.12 | 130.4 mm Hg STANDARD_DEVIATION 17.76 |
| Vital Signs: Systolic Supine | 128.5 mm Hg STANDARD_DEVIATION 13.6 | 130.0 mm Hg STANDARD_DEVIATION 15.6 | 129.1 mm Hg STANDARD_DEVIATION 13.69 | 130.9 mm Hg STANDARD_DEVIATION 16.04 | 131.3 mm Hg STANDARD_DEVIATION 19 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 26 | 21 / 23 | 23 / 26 | 24 / 24 |
| serious Total, serious adverse events | 2 / 26 | 2 / 23 | 1 / 26 | 2 / 24 |
Outcome results
Primary
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.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Tolerability of the Three Dosages(5mg, 10mg and 20mg) of Isradipine CR. | 25 participants |
| Isradipine CR 5mg/Day | Tolerability of the Three Dosages(5mg, 10mg and 20mg) of Isradipine CR. | 19 participants |
| Isradipine CR 10mg/Day | Tolerability of the Three Dosages(5mg, 10mg and 20mg) of Isradipine CR. | 19 participants |
| Isradipine CR 15-20mg/Day | Tolerability of the Three Dosages(5mg, 10mg and 20mg) of Isradipine CR. | 9 participants |
Comparison: The tolerability of 5mg/day dosage of isradipine CR will be compared with that of the placebo group using one-sided Fisher's exact tests. No adjustment will be made for multiple comparisons in these analyses.p-value: 0.138395% CI: [0.0196, 1.8411]Fisher Exact
Comparison: The tolerability of 10mg/day dosage of isradipine CR will be compared with that of the placebo group using one-sided Fisher's exact tests. No adjustment will be made for multiple comparisons in these analyses.p-value: 0.024895% CI: [0.0123, 0.9591]Fisher Exact
Comparison: The tolerability of 20mg/day dosage of isradipine CR will be compared with that of the placebo group using one-sided Fisher's exact tests. No adjustment will be made for multiple comparisons in these analyses.p-value: <0.000195% CI: [0.0028, 0.2087]Fisher Exact
Secondary
Common Adverse Events: Back Pain
Musculoskeletal and Connective Tissue Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Back Pain | 1 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Back Pain | 0 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Back Pain | 2 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Back Pain | 3 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Back Pain.p-value: 0.595% CI: [0.1771, 24.5057]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Back Pain.p-value: 0.274695% CI: [0.3453, 36.9408]Fisher Exact
Secondary
Common Adverse Events: Constipation
Gastrointestinal Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Constipation | 3 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Constipation | 2 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Constipation | 3 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Constipation | 4 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Constipation.p-value: 0.66695% CI: [0.1824, 5.482]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Constipation.p-value: 0.785295% CI: [0.1109, 4.8065]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Constipation.p-value: 0.453495% CI: [0.3057, 7.6897]Fisher Exact
Secondary
Common Adverse Events: Depression
Psychiatric Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Depression | 2 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Depression | 3 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Depression | 1 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Depression | 1 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Depression.p-value: 0.440295% CI: [0.2733, 11.8558]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Depression.p-value: 0.882495% CI: [0.0408, 5.6461]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Depression.p-value: 0.664195% CI: [0.1413, 8.4197]Fisher Exact
Secondary
Common Adverse Events: Diarrhoea
Gastrointestinal Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Diarrhoea | 2 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Diarrhoea | 1 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Diarrhoea | 2 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Diarrhoea | 1 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Diarrhoea.p-value: 0.858995% CI: [0.0462, 6.4433]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Diarrhoea.p-value: 0.695195% CI: [0.13, 7.6906]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Diarrhoea.p-value: 0.867395% CI: [0.0442, 6.1537]Fisher Exact
Secondary
Common Adverse Events: Dizziness
Nervous system disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Dizziness | 7 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Dizziness | 5 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Dizziness | 6 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Dizziness | 6 participants |
Comparison: one-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Dizziness.p-value: 0.773595% CI: [0.2022, 2.812]Fisher Exact
Comparison: one-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Dizziness.p-value: 0.738595% CI: [0.2314, 2.8658]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Dizziness.p-value: 0.682395% CI: [0.2549, 3.2112]Fisher Exact
Secondary
Common Adverse Events: Dyspepsia
Gastrointestinal Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Dyspepsia | 3 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Dyspepsia | 1 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Dyspepsia | 1 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Dyspepsia | 1 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Dyspepsia .p-value: 0.929495% CI: [0.0337, 3.6084]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Dyspepsia .p-value: 0.944895% CI: [0.0297, 3.1612]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Dyspepsia .p-value: 0.935195% CI: [0.0322, 3.4459]Fisher Exact
Secondary
Common Adverse Events: Fatigue
General Disorders and Administration Site Conditions. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Fatigue | 2 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Fatigue | 1 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Fatigue | 3 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Fatigue | 3 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Fatigue.p-value: 0.858995% CI: [0.0462, 6.4433]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Fatigue.p-value: 0.595% CI: [0.2392, 10.241]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Fatigue.p-value: 0.460995% CI: [0.2609, 11.2639]Fisher Exact
Secondary
Common Adverse Events: Headache
Nervous System disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Headache | 3 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Headache | 3 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Headache | 6 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Headache | 4 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Headache.p-value: 0.604995% CI: [0.2082, 6.3508]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Headache.p-value: 0.232795% CI: [0.5081, 10.4105]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Headache.p-value: 0.453495% CI: [0.3057, 7.6897]Fisher Exact
Secondary
Common Adverse Events: Hypotension
Vascular Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Hypotension | 1 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Hypotension | 1 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Hypotension | 2 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Hypotension | 2 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Hypotension.p-value: 0.723695% CI: [0.067, 19.264]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Hypotension.p-value: 0.595% CI: [0.1771, 24.5057]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Hypotension.p-value: 0.469495% CI: [0.1926, 26.8124]Fisher Exact
Secondary
Common Adverse Events: Insomnia
Psychiatric Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Insomnia | 2 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Insomnia | 3 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Insomnia | 1 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Insomnia | 1 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Insomnia .p-value: 0.440295% CI: [0.2733, 11.8558]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Insomnia .p-value: 0.882495% CI: [0.0408, 5.6461]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Insomnia .p-value: 0.867395% CI: [0.0442, 6.1537]Fisher Exact
Secondary
Common Adverse Events: Nasopharyngitis
Infections and infestations. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Nasopharyngitis | 2 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Nasopharyngitis | 4 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Nasopharyngitis | 7 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Nasopharyngitis | 4 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Nasopharyngitis.p-value: 0.275695% CI: [0.4172, 15.2975]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Nasopharyngitis.p-value: 0.0795% CI: [0.8217, 23.7875]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Nasopharyngitis.p-value: 0.295395% CI: [0.3975, 14.4919]Fisher Exact
Secondary
Common Adverse Events: Nausea
Gastrointestinal Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Nausea | 3 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Nausea | 2 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Nausea | 1 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Nausea | 2 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Nausea.p-value: 0.785295% CI: [0.1109, 4.8065]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Nausea.p-value: 0.944895% CI: [0.0297, 3.1612]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Nausea.p-value: 0.799695% CI: [0.1061, 4.5779]Fisher Exact
Secondary
Common Adverse Events: Oedema Peripheral
General disorders and administration site conditions. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Oedema Peripheral | 1 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Oedema Peripheral | 4 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Oedema Peripheral | 10 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Oedema Peripheral | 16 participants |
Comparison: The analyses is to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Oedema Peripheral.p-value: 0.138495% CI: [0.5432, 50.9977]Fisher Exact
Comparison: Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Oedema Peripheral.p-value: 0.002495% CI: [1.8214, 134.0403]Fisher Exact
Comparison: Fisher's exact test will be used to compare Isradipine CR 20mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Oedema Peripheral.p-value: <0.000195% CI: [5.7004, 438.5694]Fisher Exact
Secondary
Common Adverse Events: Sinusitis
Infections and Infestations. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Sinusitis | 3 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Sinusitis | 2 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Sinusitis | 1 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Sinusitis | 0 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Sinusitis.p-value: 0.785295% CI: [0.1109, 4.8065]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Sinusitis.p-value: 0.944895% CI: [0.0297, 3.1612]Fisher Exact
Secondary
Common Adverse Events: Somnolence
Nervous System Disorders. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Somnolence | 2 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Somnolence | 3 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Somnolence | 2 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Somnolence | 0 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Somnolence.p-value: 0.440295% CI: [0.2733, 11.8558]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Somnolence.p-value: 0.695195% CI: [0.13, 7.6906]Fisher Exact
Secondary
Common Adverse Events: Upper Respiratory Tract Infection
Infections and Infestations. Common adverse experience/event is defined as AE occurs to 5(about 5%) or more subjects. They will also be tabulated by treatment groups.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Common Adverse Events: Upper Respiratory Tract Infection | 1 participants |
| Isradipine CR 5mg/Day | Common Adverse Events: Upper Respiratory Tract Infection | 2 participants |
| Isradipine CR 10mg/Day | Common Adverse Events: Upper Respiratory Tract Infection | 5 participants |
| Isradipine CR 15-20mg/Day | Common Adverse Events: Upper Respiratory Tract Infection | 0 participants |
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 5mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Tract Infection.p-value: 0.453295% CI: [0.2015, 28.1366]Fisher Exact
Comparison: One-sided Fisher's exact test will be used to compare Isradipine CR 10mg group to the placebo group with regard to the proportion of subjects experiencing the adverse event of Tract Infection.p-value: 0.095395% CI: [0.6439, 55.0272]Fisher Exact
Secondary
Efficacy: Change in Activities of Daily Living(ADL) Subscale of the Unified Parkinson's Disease Rating Scale
The outcome is defined as change in ADL subscale of the Unified Parkinson's Disease Rating Scale(UPDRS Part II) between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. UPDRS Part II: Activities of Daily Living in the week prior to the designated visit, consisting of 13 questions answered on a 0-4 point scale where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Total Part II score represents the sum of these 13 questions. A greater increase in score indicates a greater increase in disability. A total of 52 points are possible. 52 represents the worst (total) disability), 0--no disability
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
Population: All participants were included in the primary and secondary outcome analyses
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy: Change in Activities of Daily Living(ADL) Subscale of the Unified Parkinson's Disease Rating Scale | 2.60 units on a scale | Standard Error 0.56 |
| Isradipine CR 5mg/Day | Efficacy: Change in Activities of Daily Living(ADL) Subscale of the Unified Parkinson's Disease Rating Scale | 3.20 units on a scale | Standard Error 0.6 |
| Isradipine CR 10mg/Day | Efficacy: Change in Activities of Daily Living(ADL) Subscale of the Unified Parkinson's Disease Rating Scale | 2.09 units on a scale | Standard Error 0.56 |
| Isradipine CR 15-20mg/Day | Efficacy: Change in Activities of Daily Living(ADL) Subscale of the Unified Parkinson's Disease Rating Scale | 1.86 units on a scale | Standard Error 0.59 |
Comparison: Change in ADL UPDRS subscale of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.464895% CI: [-1.03, 2.23]ANCOVA
Comparison: Change in ADL UPDRS subscale of Isradipine CR 10mg/day arm is compared to placebo group.p-value: 0.52595% CI: [-2.09, 1.07]ANCOVA
Comparison: Change in ADL UPDRS subscale of Isradipine CR 20mg/day arm is compared to placebo group.p-value: 0.367495% CI: [-2.36, 0.88]ANCOVA
Secondary
Efficacy: Change in Beck Depression Inventory II (BDI-II)
The Beck Depression Inventory (BDI) is a validated self-reported 21-item depression scale that was tested and validated as a reliable instrument for screening for depression in PD. The outcome is defined as change in BDI-II between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. Total BDI score represents the sum of these 21-items. A higher change in score indicates a greater increase in disability. Total score of 0-13 is considered minimal, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
Population: All participants were included in primary and secondary outcome analyses
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy: Change in Beck Depression Inventory II (BDI-II) | -0.52 units on a scale | Standard Error 0.93 |
| Isradipine CR 5mg/Day | Efficacy: Change in Beck Depression Inventory II (BDI-II) | 1.99 units on a scale | Standard Error 0.93 |
| Isradipine CR 10mg/Day | Efficacy: Change in Beck Depression Inventory II (BDI-II) | 0.11 units on a scale | Standard Error 0.98 |
| Isradipine CR 15-20mg/Day | Efficacy: Change in Beck Depression Inventory II (BDI-II) | 1.50 units on a scale | Standard Error 0.95 |
Comparison: Change in BDI-II of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.060895% CI: [-0.12, 5.13]ANCOVA
Comparison: Change in BDI-II of Isradipine CR 10mg/day arm is compared to placebo group.p-value: 0.644595% CI: [-2.07, 3.33]ANCOVA
Comparison: Change in BDI-II of Isradipine CR 20mg/day arm is compared to placebo group.p-value: 0.133695% CI: [-0.63, 4.67]ANCOVA
Secondary
Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale
The outcome is defined as change in Mental subscale of Unified Parkinson's Disease Rating Scale(UPDRS Part I) between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. UPDRS Part I: Mentation, behavior and mood, consisting of 4 questions answered on a 0-4 point scale where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Total score represents the sum of these 4 questions. A greater increase in score indicates a greater increase in disability. A total of 16 points are possible. 16 represents the worst (total) disability), 0--no disability.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
Population: All participants were used in primary and secondary outcome analyses
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale | 0.30 units on a scale | Standard Error 0.26 |
| Isradipine CR 5mg/Day | Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale | 0.76 units on a scale | Standard Error 0.28 |
| Isradipine CR 10mg/Day | Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale | 0.30 units on a scale | Standard Error 0.26 |
| Isradipine CR 15-20mg/Day | Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale | 0.03 units on a scale | Standard Error 0.27 |
Comparison: Change in Mental UPDRS subscale of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.232495% CI: [-0.3, 1.22]ANCOVA
Comparison: Change in Mental UPDRS subscale of Isradipine CR 10mg/day arm is compared to placebo group.p-value: 195% CI: [-0.73, 0.73]ANCOVA
Comparison: Change in Mental UPDRS subscale of Isradipine CR 20mg/day arm is compared to placebo group.p-value: 0.467595% CI: [-1.02, 0.47]ANCOVA
Secondary
Efficacy: Change in Modified Hoehn & Yahr Scale
The Modified Hoehn & Yahr Scale is an 8-level Parkinson's disease staging instrument. The outcome is defined as change in Modified Hoehn & Yahr Scale between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. A greater increase in stage indicates a greater increase in disability. Stage ranges from 0-5 (also including 1.5 and 2.5) with 0 indicating no disability and 5 indicating maximum disability.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
Population: All participants were included in primary and secondary outcome analyses
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy: Change in Modified Hoehn & Yahr Scale | 0.27 units on a scale | Standard Error 0.08 |
| Isradipine CR 5mg/Day | Efficacy: Change in Modified Hoehn & Yahr Scale | 0.22 units on a scale | Standard Error 0.08 |
| Isradipine CR 10mg/Day | Efficacy: Change in Modified Hoehn & Yahr Scale | 0.12 units on a scale | Standard Error 0.08 |
| Isradipine CR 15-20mg/Day | Efficacy: Change in Modified Hoehn & Yahr Scale | 0.11 units on a scale | Standard Error 0.08 |
Comparison: Change in Modified Hoehn \& Yahr Scale of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.667795% CI: [-0.27, 0.17]ANCOVA
Comparison: Change in Modified Hoehn \& Yahr Scale of Isradipine CR 10mg/day arm is compared to placebo group.p-value: 0.175595% CI: [-0.36, 0.07]ANCOVA
Comparison: Change in Modified Hoehn \& Yahr Scale of Isradipine CR 20mg/day arm is compared to placebo group.p-value: 0.146395% CI: [-0.38, 0.06]ANCOVA
Secondary
Efficacy: Change in Modified Schwab & England Independence Scale
The Schwab & England scale is an investigator and subject assessment of the subject's level of independence at all scheduled study visits. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson's disease appeared. The outcome is defined as change in Schwab & England Independence Scale between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. Higher decrease in score indicates higher disability. Score ranges from 100% (complete independence) to 0% (total disability).
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
Population: All participants were included in primary and secondary outcome analyses
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy: Change in Modified Schwab & England Independence Scale | -5.04 units on a scale | Standard Error 0.96 |
| Isradipine CR 5mg/Day | Efficacy: Change in Modified Schwab & England Independence Scale | -5.56 units on a scale | Standard Error 1.02 |
| Isradipine CR 10mg/Day | Efficacy: Change in Modified Schwab & England Independence Scale | -3.69 units on a scale | Standard Error 0.96 |
| Isradipine CR 15-20mg/Day | Efficacy: Change in Modified Schwab & England Independence Scale | -3.76 units on a scale | Standard Error 1.01 |
Comparison: Change in Modified Schwab \& England Independence Scale of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.711195% CI: [-3.3, 2.26]ANCOVA
Comparison: Change in Modified Schwab \& England Independence Scale of Isradipine CR 10mg/day arm is compared to placebo group.p-value: 0.323795% CI: [-1.35, 4.04]ANCOVA
Comparison: Change in Modified Schwab \& England Independence Scale of Isradipine CR 20mg/day arm is compared to placebo group.p-value: 0.365895% CI: [-1.51, 4.05]ANCOVA
Secondary
Efficacy: Change in Montreal Cognitive Assessment
The Montreal Cognitive Assessment(MoCA) is a brief 30-point screening instrument that was developed and validated to identify subjects with mild cognitive impairment. The outcome is defined as change in MoCA between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. Total MoCA score represents the sum of these 30-points, with a lower score indicating greater cognitive impairment. 30 is the maximum score, with a score of 26 or higher considered normal and below 26 indicative of Mild Cognitive Impairment.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
Population: All participants were included in primary and secondary outcome analyses
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy: Change in Montreal Cognitive Assessment | 0.58 units on a scale | Standard Error 0.4 |
| Isradipine CR 5mg/Day | Efficacy: Change in Montreal Cognitive Assessment | 0.06 units on a scale | Standard Error 0.38 |
| Isradipine CR 10mg/Day | Efficacy: Change in Montreal Cognitive Assessment | 0.11 units on a scale | Standard Error 0.41 |
| Isradipine CR 15-20mg/Day | Efficacy: Change in Montreal Cognitive Assessment | 0.36 units on a scale | Standard Error 0.4 |
Comparison: Change in Montreal Cognitive Assessment of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.353395% CI: [-1.64, 0.59]ANCOVA
Comparison: Change in Montreal Cognitive Assessment of Isradipine CR 10mg/day arm is compared to placebo group.p-value: 0.404595% CI: [-1.59, 0.65]ANCOVA
Comparison: Change in Montreal Cognitive Assessment of Isradipine CR 20mg/day arm is compared to placebo group.p-value: 0.704995% CI: [-1.36, 0.92]ANCOVA
Secondary
Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale
The outcome is defined as change in Motor subscale of the Unified Parkinson's Disease Rating Scale(UPDRS Part III) between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. UPDRS Part III: motor abilities at the time of the visit, consisting of 27 items (including 13 general questions and 14 sub-questions) each answered on a 0-4 point scale where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Total Part III score represents the sum of these 27 items. A total of 108 points are possible. 108 represents the worst (total) disability), 0--no disability.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
Population: All participants were included in primary and secondary outcome analyses
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale | 4.32 units on a scale | Standard Error 1.03 |
| Isradipine CR 5mg/Day | Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale | 3.49 units on a scale | Standard Error 1.09 |
| Isradipine CR 10mg/Day | Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale | 3.91 units on a scale | Standard Error 1.03 |
| Isradipine CR 15-20mg/Day | Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale | 3.69 units on a scale | Standard Error 1.07 |
Comparison: Change in Motor UPDRS subscale of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.57995% CI: [-3.8, 2.14]ANCOVA
Comparison: Change in Motor UPDRS subscale of Isradipine CR 10mg/day arm is compared to placebo group.p-value: 0.777895% CI: [-3.3, 2.48]ANCOVA
Comparison: Change in Motor UPDRS subscale of Isradipine CR 20mg/day arm is compared to placebo group.p-value: 0.66995% CI: [-3.58, 2.31]ANCOVA
Secondary
Efficacy: Change in Parkinson Disease Quality of Life Questionnaire-39(PDQ-39)
The PD Quality of Life Scale(PDQ-39) asks the subject to evaluate how Parkinson disease has affected their health and overall quality of life at that point in time. The total quality of life scale includes subscales relating to social role, self-image/sexuality, sleep, outlook, physical function and urinary function. The outcome is defined as change in PDQ-39 between the baseline visit and month 12 or the time of sufficient disability to require dopaminergic therapy. It is scored on a scale of zero to 100, with lower scores indicating better health and higher scores more severe disability.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
Population: All participants were included in primary and secondary outcome analyses
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy: Change in Parkinson Disease Quality of Life Questionnaire-39(PDQ-39) | 1.28 units on a scale | Standard Error 1.28 |
| Isradipine CR 5mg/Day | Efficacy: Change in Parkinson Disease Quality of Life Questionnaire-39(PDQ-39) | 3.47 units on a scale | Standard Error 1.27 |
| Isradipine CR 10mg/Day | Efficacy: Change in Parkinson Disease Quality of Life Questionnaire-39(PDQ-39) | 3.00 units on a scale | Standard Error 1.35 |
| Isradipine CR 15-20mg/Day | Efficacy: Change in Parkinson Disease Quality of Life Questionnaire-39(PDQ-39) | 3.35 units on a scale | Standard Error 1.31 |
Comparison: Change in PDQ-39 of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.227895% CI: [-1.4, 5.79]ANCOVA
Comparison: Change in PDQ-39 of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.35695% CI: [-1.97, 5.42]ANCOVA
Comparison: Change in PDQ-39 of Isradipine CR 20mg/day arm is compared to placebo group.p-value: 0.2695% CI: [-1.56, 5.71]ANCOVA
Secondary
Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS)
Outcome is defined as change in total Unified Parkinson's Disease Rating Scale (UPDRS) between the baseline visit and month 12 or the time to require dopaminergic therapy (last visit before subject goes on dopaminergic therapy), whichever occurs first. The UPDRS score has 4 components. Part I assesses mentation; Part II assesses activities of daily living; Part III assesses motor abilities; Part IV assesses complications of therapy. A total of 44 items are included in Parts I-III. Each item will receive a score ranging from 0 to 4 where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Part IV contains 11 items, 4 of these items are scored 0-4 in the same manner, and 7 are scored 0-1, with 0 indicating the absence of impairment and 1 indicating the presence of impairment. Total UPDRS score represents the sum of these items in Parts I-IV. A total of 199 points are possible. 199 represents the worst (total) disability), 0--no disability.
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
Population: Participants are 99 subjects with early Parkinson disease not requiring dopaminergic therapy.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS) | 7.40 Scores on a scale | Standard Error 1.39 |
| Isradipine CR 5mg/Day | Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS) | 7.44 Scores on a scale | Standard Error 1.48 |
| Isradipine CR 10mg/Day | Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS) | 6.30 Scores on a scale | Standard Error 1.39 |
| Isradipine CR 15-20mg/Day | Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS) | 5.40 Scores on a scale | Standard Error 1.45 |
Comparison: Change in UPDRS total score of Isradipine CR 5mg/day arm is compared to placebo group.p-value: 0.983495% CI: [-3.99, 4.07]ANCOVA
Comparison: Change in UPDRS total score of Isradipine CR 10mg/day arm is compared to placebo group.p-value: 0.576195% CI: [-5.01, 2.8]ANCOVA
Comparison: Change in UPDRS total score of Isradipine CR 20mg/day arm is compared to placebo group.p-value: 0.32295% CI: [-5.98, 1.99]ANCOVA
Secondary
Vital Signs: Change in Diastolic Standing
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Vital Signs: Change in Diastolic Standing | -0.38 mm Hg | Standard Error 1.44 |
| Isradipine CR 5mg/Day | Vital Signs: Change in Diastolic Standing | -4.20 mm Hg | Standard Error 1.57 |
| Isradipine CR 10mg/Day | Vital Signs: Change in Diastolic Standing | -5.14 mm Hg | Standard Error 1.5 |
| Isradipine CR 15-20mg/Day | Vital Signs: Change in Diastolic Standing | -4.34 mm Hg | Standard Error 1.69 |
Secondary
Vital Signs: Change in Diastolic Supine
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Vital Signs: Change in Diastolic Supine | 0.09 mm Hg | Standard Error 1.27 |
| Isradipine CR 5mg/Day | Vital Signs: Change in Diastolic Supine | -2.79 mm Hg | Standard Error 1.38 |
| Isradipine CR 10mg/Day | Vital Signs: Change in Diastolic Supine | -4.54 mm Hg | Standard Error 1.32 |
| Isradipine CR 15-20mg/Day | Vital Signs: Change in Diastolic Supine | -3.63 mm Hg | Standard Error 1.49 |
Secondary
Vital Signs: Change in Pulse Standing
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Vital Signs: Change in Pulse Standing | -0.08 beats per minute | Standard Error 1.89 |
| Isradipine CR 5mg/Day | Vital Signs: Change in Pulse Standing | -2.98 beats per minute | Standard Error 2.07 |
| Isradipine CR 10mg/Day | Vital Signs: Change in Pulse Standing | -2.29 beats per minute | Standard Error 1.97 |
| Isradipine CR 15-20mg/Day | Vital Signs: Change in Pulse Standing | -1.21 beats per minute | Standard Error 2.23 |
Secondary
Vital Signs: Change in Pulse Supine
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Vital Signs: Change in Pulse Supine | -0.42 beats per minute | Standard Error 1.55 |
| Isradipine CR 5mg/Day | Vital Signs: Change in Pulse Supine | -0.71 beats per minute | Standard Error 1.69 |
| Isradipine CR 10mg/Day | Vital Signs: Change in Pulse Supine | -0.52 beats per minute | Standard Error 1.62 |
| Isradipine CR 15-20mg/Day | Vital Signs: Change in Pulse Supine | 0.18 beats per minute | Standard Error 1.83 |
Secondary
Vital Signs: Change in Systolic Standing
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Vital Signs: Change in Systolic Standing | -4.77 mm Hg | Standard Error 2.49 |
| Isradipine CR 5mg/Day | Vital Signs: Change in Systolic Standing | -9.85 mm Hg | Standard Error 2.71 |
| Isradipine CR 10mg/Day | Vital Signs: Change in Systolic Standing | -7.75 mm Hg | Standard Error 2.6 |
| Isradipine CR 15-20mg/Day | Vital Signs: Change in Systolic Standing | -6.30 mm Hg | Standard Error 2.94 |
Secondary
Vital Signs: Change in Systolic Supine
Time frame: Baseline to 12 months or the time to require dopaminergic therapy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Vital Signs: Change in Systolic Supine | -2.45 mm Hg | Standard Error 2.25 |
| Isradipine CR 5mg/Day | Vital Signs: Change in Systolic Supine | -8.59 mm Hg | Standard Error 2.45 |
| Isradipine CR 10mg/Day | Vital Signs: Change in Systolic Supine | -6.45 mm Hg | Standard Error 2.34 |
| Isradipine CR 15-20mg/Day | Vital Signs: Change in Systolic Supine | -7.01 mm Hg | Standard Error 2.65 |