Trial Outcomes & Findings for Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease (NCT NCT00909545)

NCT ID: NCT00909545

Last Updated: 2013-04-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 99 participants
• Primary outcome timeframe: Baseline to 12 months or the time to require dopaminergic therapy
• Results posted on: 2013-04-17

Participant Flow

Participant milestones

Measure	Placebo 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day 3-4 Dynacirc CR 5mg tablets once daily
Overall Study STARTED	26	23	26	24
Overall Study COMPLETED	25	22	25	19
Overall Study NOT COMPLETED	1	1	1	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 20mg/Day n=24 Participants 4 Dynacirc CR 5mg tablets once daily	Total n=99 Participants Total of all reporting groups
Age Continuous	60.2 years STANDARD_DEVIATION 10.1 • n=5 Participants	57.7 years STANDARD_DEVIATION 8.3 • n=7 Participants	58.5 years STANDARD_DEVIATION 11.6 • n=5 Participants	59.8 years STANDARD_DEVIATION 8.9 • n=4 Participants	59.1 years STANDARD_DEVIATION 9.8 • n=21 Participants
Age, Customized Between 30 and 65 years	17 participants n=5 Participants	18 participants n=7 Participants	18 participants n=5 Participants	19 participants n=4 Participants	72 participants n=21 Participants
Age, Customized >=65 years	9 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants	5 participants n=4 Participants	27 participants n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	8 Participants n=4 Participants	30 Participants n=21 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	15 Participants n=7 Participants	17 Participants n=5 Participants	16 Participants n=4 Participants	69 Participants n=21 Participants
Race/Ethnicity, Customized White	25 participants n=5 Participants	22 participants n=7 Participants	22 participants n=5 Participants	22 participants n=4 Participants	91 participants n=21 Participants
Race/Ethnicity, Customized Other race	1 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	2 participants n=4 Participants	8 participants n=21 Participants
Region of Enrollment United States	24 participants n=5 Participants	21 participants n=7 Participants	24 participants n=5 Participants	21 participants n=4 Participants	90 participants n=21 Participants
Region of Enrollment Canada	2 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	9 participants n=21 Participants
Unified Parkinson's Disease Rating Scale (UPDRS) Total	25.46 Unit of UPDRS scales STANDARD_DEVIATION 9.39 • n=5 Participants	26.43 Unit of UPDRS scales STANDARD_DEVIATION 9.69 • n=7 Participants	23.65 Unit of UPDRS scales STANDARD_DEVIATION 9.97 • n=5 Participants	24.67 Unit of UPDRS scales STANDARD_DEVIATION 10.77 • n=4 Participants	25.0 Unit of UPDRS scales STANDARD_DEVIATION 9.9 • n=21 Participants
Unified Parkinson's Disease Rating Scale (UPDRS) Mental	0.65 Unit of UPDRS scales STANDARD_DEVIATION 1.06 • n=5 Participants	1.30 Unit of UPDRS scales STANDARD_DEVIATION 1.79 • n=7 Participants	0.65 Unit of UPDRS scales STANDARD_DEVIATION 0.98 • n=5 Participants	0.96 Unit of UPDRS scales STANDARD_DEVIATION 1.12 • n=4 Participants	0.9 Unit of UPDRS scales STANDARD_DEVIATION 1.3 • n=21 Participants
Unified Parkinson's Disease Rating Scale (UPDRS) Activities of Daily Living (ADL)	5.85 Unit of UPDRS scales STANDARD_DEVIATION 2.98 • n=5 Participants	5.83 Unit of UPDRS scales STANDARD_DEVIATION 3.02 • n=7 Participants	6.15 Unit of UPDRS scales STANDARD_DEVIATION 3.03 • n=5 Participants	6.58 Unit of UPDRS scales STANDARD_DEVIATION 3.03 • n=4 Participants	6.1 Unit of UPDRS scales STANDARD_DEVIATION 3.0 • n=21 Participants
Unified Parkinson's Disease Rating Scale (UPDRS) Motor	18.96 Unit of UPDRS scales STANDARD_DEVIATION 7.27 • n=5 Participants	19.30 Unit of UPDRS scales STANDARD_DEVIATION 8.02 • n=7 Participants	16.85 Unit of UPDRS scales STANDARD_DEVIATION 7.88 • n=5 Participants	17.13 Unit of UPDRS scales STANDARD_DEVIATION 8.26 • n=4 Participants	18.0 Unit of UPDRS scales STANDARD_DEVIATION 7.8 • n=21 Participants
Hoehn & Yahr Scale H/Y Stage: 1	7 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	11 Participants n=4 Participants	30 Participants n=21 Participants
Hoehn & Yahr Scale H/Y Stage: 1.5	2 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Hoehn & Yahr Scale H/Y Stage: 2	16 Participants n=5 Participants	16 Participants n=7 Participants	18 Participants n=5 Participants	11 Participants n=4 Participants	61 Participants n=21 Participants
Hoehn & Yahr Scale H/Y Stage: 2.5	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Modified Schwab & England Independence Scale	93.08 Percentage scale STANDARD_DEVIATION 5.11 • n=5 Participants	93.48 Percentage scale STANDARD_DEVIATION 4.632 • n=7 Participants	93.08 Percentage scale STANDARD_DEVIATION 5.11 • n=5 Participants	91.04 Percentage scale STANDARD_DEVIATION 5.10 • n=4 Participants	92.0 Percentage scale STANDARD_DEVIATION 5.0 • n=21 Participants
Montreal Cognitive Assessment	26.96 Unit of MoCA STANDARD_DEVIATION 2.58 • n=5 Participants	27.96 Unit of MoCA STANDARD_DEVIATION 1.97 • n=7 Participants	26.92 Unit of MoCA STANDARD_DEVIATION 2.36 • n=5 Participants	27.79 Unit of MoCA STANDARD_DEVIATION 1.89 • n=4 Participants	27.4 Unit of MoCA STANDARD_DEVIATION 2.2 • n=21 Participants
PD Qualify of Life Scale	10.28 Unit of PDQ-39 STANDARD_DEVIATION 8.55 • n=5 Participants	9.69 Unit of PDQ-39 STANDARD_DEVIATION 6.88 • n=7 Participants	8.39 Unit of PDQ-39 STANDARD_DEVIATION 5.82 • n=5 Participants	10.45 Unit of PDQ-39 STANDARD_DEVIATION 8.06 • n=4 Participants	9.7 Unit of PDQ-39 STANDARD_DEVIATION 2.3 • n=21 Participants
Vital Signs: Systolic Standing	130.0 mm Hg STANDARD_DEVIATION 18.12 • n=5 Participants	127.3 mm Hg STANDARD_DEVIATION 17.03 • n=7 Participants	130.4 mm Hg STANDARD_DEVIATION 17.76 • n=5 Participants	125.8 mm Hg STANDARD_DEVIATION 11.96 • n=4 Participants	128.4 mm Hg STANDARD_DEVIATION 16.3 • n=21 Participants
Vital Signs: Systolic Supine	130.9 mm Hg STANDARD_DEVIATION 16.04 • n=5 Participants	128.5 mm Hg STANDARD_DEVIATION 13.60 • n=7 Participants	131.3 mm Hg STANDARD_DEVIATION 19.00 • n=5 Participants	129.1 mm Hg STANDARD_DEVIATION 13.69 • n=4 Participants	130.0 mm Hg STANDARD_DEVIATION 15.6 • n=21 Participants
Vital Signs: Diastolic Standing	83.73 mm Hg STANDARD_DEVIATION 12.74 • n=5 Participants	84.43 mm Hg STANDARD_DEVIATION 12.22 • n=7 Participants	80.04 mm Hg STANDARD_DEVIATION 9.73 • n=5 Participants	81.29 mm Hg STANDARD_DEVIATION 11.02 • n=4 Participants	82.3 mm Hg STANDARD_DEVIATION 11.4 • n=21 Participants
Vital Signs: Diastolic Supine	80.69 mm Hg STANDARD_DEVIATION 11.34 • n=5 Participants	79.22 mm Hg STANDARD_DEVIATION 9.50 • n=7 Participants	76.88 mm Hg STANDARD_DEVIATION 10.95 • n=5 Participants	79.63 mm Hg STANDARD_DEVIATION 10.43 • n=4 Participants	79.1 mm Hg STANDARD_DEVIATION 10.5 • n=21 Participants
Vital Signs: Pulse Standing	72.92 Beats per minute STANDARD_DEVIATION 11.90 • n=5 Participants	77.35 Beats per minute STANDARD_DEVIATION 10.70 • n=7 Participants	75.50 Beats per minute STANDARD_DEVIATION 12.27 • n=5 Participants	72.33 Beats per minute STANDARD_DEVIATION 11.43 • n=4 Participants	74.5 Beats per minute STANDARD_DEVIATION 11.6 • n=21 Participants
Vital Signs: Pulse Supine	68.00 Beats per minute STANDARD_DEVIATION 10.63 • n=5 Participants	67.43 Beats per minute STANDARD_DEVIATION 10.28 • n=7 Participants	67.08 Beats per minute STANDARD_DEVIATION 8.39 • n=5 Participants	66.33 Beats per minute STANDARD_DEVIATION 9.71 • n=4 Participants	67.2 Beats per minute STANDARD_DEVIATION 9.6 • n=21 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Tolerability of the Three Dosages(5mg, 10mg and 20mg) of Isradipine CR.	25 participants	19 participants	19 participants	9 participants

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Population: Participants are 99 subjects with early Parkinson disease not requiring 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Efficacy: Change in Unified Parkinson's Disease Rating Scale (UPDRS)	7.40 Scores on a scale Standard Error 1.39	7.44 Scores on a scale Standard Error 1.48	6.30 Scores on a scale Standard Error 1.39	5.40 Scores on a scale Standard Error 1.45

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Population: All participants were used in primary and secondary outcome analyses

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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Efficacy: Change in Mental Subscales of the Unified Parkinson's Disease Rating Scale	0.30 units on a scale Standard Error 0.26	0.76 units on a scale Standard Error 0.28	0.30 units on a scale Standard Error 0.26	0.03 units on a scale Standard Error 0.27

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Population: All participants were included in the primary and secondary outcome analyses

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

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
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	3.20 units on a scale Standard Error 0.60	2.09 units on a scale Standard Error 0.56	1.86 units on a scale Standard Error 0.59

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Population: All participants were included in primary and secondary outcome analyses

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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Efficacy: Change in Motor Subscale of the Unified Parkinson's Disease Rating Scale	4.32 units on a scale Standard Error 1.03	3.49 units on a scale Standard Error 1.09	3.91 units on a scale Standard Error 1.03	3.69 units on a scale Standard Error 1.07

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Population: All participants were included in primary and secondary outcome analyses

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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Efficacy: Change in Modified Hoehn & Yahr Scale	0.27 units on a scale Standard Error 0.08	0.22 units on a scale Standard Error 0.08	0.12 units on a scale Standard Error 0.08	0.11 units on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Population: All participants were included in primary and secondary outcome analyses

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).

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Efficacy: Change in Modified Schwab & England Independence Scale	-5.04 units on a scale Standard Error 0.96	-5.56 units on a scale Standard Error 1.02	-3.69 units on a scale Standard Error 0.96	-3.76 units on a scale Standard Error 1.01

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Population: All participants were included in primary and secondary outcome analyses

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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Efficacy: Change in Beck Depression Inventory II (BDI-II)	-0.52 units on a scale Standard Error 0.93	1.99 units on a scale Standard Error 0.93	0.11 units on a scale Standard Error 0.98	1.50 units on a scale Standard Error 0.95

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Population: All participants were included in primary and secondary outcome analyses

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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Efficacy: Change in Montreal Cognitive Assessment	0.58 units on a scale Standard Error 0.40	0.06 units on a scale Standard Error 0.38	0.11 units on a scale Standard Error 0.41	0.36 units on a scale Standard Error 0.40

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Population: All participants were included in primary and secondary outcome analyses

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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Efficacy: Change in Parkinson Disease Quality of Life Questionnaire-39(PDQ-39)	1.28 units on a scale Standard Error 1.28	3.47 units on a scale Standard Error 1.27	3.00 units on a scale Standard Error 1.35	3.35 units on a scale Standard Error 1.31

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Vital Signs: Change in Systolic Standing	-4.77 mm Hg Standard Error 2.49	-9.85 mm Hg Standard Error 2.71	-7.75 mm Hg Standard Error 2.60	-6.30 mm Hg Standard Error 2.94

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Vital Signs: Change in Systolic Supine	-2.45 mm Hg Standard Error 2.25	-8.59 mm Hg Standard Error 2.45	-6.45 mm Hg Standard Error 2.34	-7.01 mm Hg Standard Error 2.65

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Vital Signs: Change in Diastolic Standing	-0.38 mm Hg Standard Error 1.44	-4.20 mm Hg Standard Error 1.57	-5.14 mm Hg Standard Error 1.50	-4.34 mm Hg Standard Error 1.69

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Vital Signs: Change in Diastolic Supine	0.09 mm Hg Standard Error 1.27	-2.79 mm Hg Standard Error 1.38	-4.54 mm Hg Standard Error 1.32	-3.63 mm Hg Standard Error 1.49

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Vital Signs: Change in Pulse Standing	-0.08 beats per minute Standard Error 1.89	-2.98 beats per minute Standard Error 2.07	-2.29 beats per minute Standard Error 1.97	-1.21 beats per minute Standard Error 2.23

SECONDARY outcome

Timeframe: Baseline to 12 months or the time to require dopaminergic therapy

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Vital Signs: Change in Pulse Supine	-0.42 beats per minute Standard Error 1.55	-0.71 beats per minute Standard Error 1.69	-0.52 beats per minute Standard Error 1.62	0.18 beats per minute Standard Error 1.83

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Oedema Peripheral	1 participants	4 participants	10 participants	16 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Dizziness	7 participants	5 participants	6 participants	6 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Nasopharyngitis	2 participants	4 participants	7 participants	4 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Headache	3 participants	3 participants	6 participants	4 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Constipation	3 participants	2 participants	3 participants	4 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Fatigue	2 participants	1 participants	3 participants	3 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Nausea	3 participants	2 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Upper Respiratory Tract Infection	1 participants	2 participants	5 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Depression	2 participants	3 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Somnolence	2 participants	3 participants	2 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Insomnia	2 participants	3 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Dyspepsia	3 participants	1 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Diarrhoea	2 participants	1 participants	2 participants	1 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Sinusitis	3 participants	2 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Back Pain	1 participants	0 participants	2 participants	3 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=26 Participants 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 Participants 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 Participants 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 15-20mg/Day n=24 Participants 3-4 Dynacirc CR 5mg tablets once daily
Common Adverse Events: Hypotension	1 participants	1 participants	2 participants	2 participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Isradipine CR 5mg/Day

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Isradipine CR 10mg/Day

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Isradipine CR 20mg/Day

Serious events: 2 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=26 participants at risk 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 participants at risk 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 participants at risk 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 20mg/Day n=24 participants at risk 4 Dynacirc CR 5mg tablets once daily
General disorders PYREXIA	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.3% 1/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Surgical and medical procedures VITRECTOMY	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) MALIGNANT MELANOMA IN SITU	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.2% 1/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
General disorders CHEST PAIN	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.3% 1/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.3% 1/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Nervous system disorders HYPOAESTHESIA	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.3% 1/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.2% 1/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Renal and urinary disorders RENAL FAILURE ACUTE	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).

Other adverse events

Measure	Placebo n=26 participants at risk 4 Placebo to Match (PTM) tablets once daily	Isradipine CR 5mg/Day n=23 participants at risk 1 Dynacirc CR 5mg tablet, 3 tablets placebo once daily	Isradipine CR 10mg/Day n=26 participants at risk 2 Dynacirc CR 5mg tablets, 2 tablets placebo once daily	Isradipine CR 20mg/Day n=24 participants at risk 4 Dynacirc CR 5mg tablets once daily
General disorders Oedema Peripheral	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	17.4% 4/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	38.5% 10/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	66.7% 16/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Nervous system disorders Dizziness	26.9% 7/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	21.7% 5/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	23.1% 6/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	25.0% 6/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Infections and infestations Nasopharyngitis	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	17.4% 4/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	26.9% 7/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	16.7% 4/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Nervous system disorders Headache	11.5% 3/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	13.0% 3/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	23.1% 6/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	16.7% 4/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Gastrointestinal disorders Constipation	11.5% 3/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	8.7% 2/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	11.5% 3/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	16.7% 4/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
General disorders Fatigue	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.3% 1/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	11.5% 3/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	12.5% 3/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Gastrointestinal disorders Nausea	11.5% 3/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	8.7% 2/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	8.3% 2/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Infections and infestations Upper Respiratory Tract Infection	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	8.7% 2/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	19.2% 5/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Psychiatric disorders Depression	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	13.0% 3/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.2% 1/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Nervous system disorders Somnolence	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	13.0% 3/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Psychiatric disorders Insomnia	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	13.0% 3/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.2% 1/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Gastrointestinal disorders Dyspepsia	11.5% 3/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.3% 1/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.2% 1/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Gastrointestinal disorders Diarrhoea	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.3% 1/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.2% 1/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Infections and infestations Sinusitis	11.5% 3/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	8.7% 2/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Musculoskeletal and connective tissue disorders Back Pain	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	0.00% 0/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	12.5% 3/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Vascular disorders Hypotension	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	4.3% 1/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	7.7% 2/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	8.3% 2/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	8.7% 2/23 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	3.8% 1/26 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).	8.3% 2/24 • 12 months or the time to require dopaminergic therapy All serious and most common adverse experiences/events will be listed by treatment. Most common adverse experiences/events were defined as AEs occurring more than 5 times(5%).

Additional Information

Tanya Simuni, MD

Feinberg School of Medicine, Northwestern University

Phone: 312-503-2970

Email: TSimuni@nmff.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place