Safety and Efficacy of Pramipexole and Bromocriptine Combined With L-dopa in Parkinson's Disease

Study Overview
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Brief Summary
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The objective of the study was to evaluate the efficacy and safety of SND 919 (pramipexole) tablets administered in combination with L-dopa in patients with Parkinson's disease using placebo and bromocriptine tablets as comparators in a double-blind design (phase III comparative study).

Official Title
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A Double-blind, Placebo-controlled, Randomised, Multicenter Trial to Compare the Safety and Efficacy of Oral Administration of Pramipexole up to 4.5mg and Bromocriptine up to 22.5mg Combined With L-dopa in Advanced Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Pramipexole
* Drug: Bromocriptine
* Drug: Placebo pramipexole
* Drug: Placebo bromocriptine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of Parkinson's disease (including juvenile parkinsonism) Patients who meet all of the following inclusion criteria Patients who were at least 20 years of age In- or outpatients of either sex Patients in any stage on the modified Hoehn and Yahr scale Patients being treated with L-dopa who have any of the following clinical conditions and problems Patients with the wearing-off phenomenon Patients with the on-off phenomenon Patients to whom a sufficient amount of L-dopa cannot be administered owing to the occurrence of an adverse event Patients in whom the effect of L-dopa is attenuated Patients in whom a dose increase of L-dopa has been refrained Patients with freezing phenomenon Exclusion Criteria: Patients being treated with other dopamine agonists (bromocriptine, pergolide mesylate, talipexole hydrochloride). Patients who have been treated with other dopamine agonist for at least 4 weeks before the start of the study (the day of giving informed consent) are eligible for the study Patients with a history of hypersensitivity to ergot preparations Patients with psychiatric symptoms such as confusion, hallucination, delusion, excitement, delirium, and abnormal behaviour Patients with subjective symptoms derived from orthostatic hypotension Patients with hypotension (systolic blood pressure less than 100 mmHg) Patients wiht Raynaud disease Patients with peptic ulcer Patients with complications such as severe cardiac, renal, hepatic disease etc. Patients with a current or past history of epilepsy Women who are or may be pregnant and lactating women Patients who are receiving any other investigational products or who have received any other investigational product within 6 months of the study Patients who are incompetent to give consent Others judged by the investigator or co-investigator to be ineligible as subjects

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pramipexole<br> | Drug: Pramipexole<br> <br> |
| Experimental: Bromocriptine<br> | Drug: Bromocriptine<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo pramipexole<br> <br> Drug: Placebo bromocriptine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in total score of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) |  | Baseline and week 12 | 
| Change from baseline in total score of UPDRS Part III (Motor Examination) |  | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in sores of individual items on UPDRS Part II |  | Baseline and weeks 2, 4, 6, 8, 10, 12 | 
| Changes from baseline in scores of individual items on UPDRS Part III |  | Baseline and weeks 2, 4, 6, 8, 10, 12 | 
| Change from baseline in area under the curve (AUC) in the UPDRS Part II score |  | Baseline and weeks 2, 4, 6, 8, 10, 12 | 
| Change from baseline in area under the curve (AUC) in the UPDRS Part III score |  | Baseline and weeks 2, 4, 6, 8, 10, 12 | 
| Change from baseline in total score of UPDRS Part I (mentation, behaviour and mood) |  | Baseline and weeks 2, 4, 6, 8, 10, 12 | 
| Change from baseline in total score of UPDRS Part IV (complications of therapy) |  | Baseline and weeks 2, 4, 6, 8, 10, 12 | 
| Change from baseline in total score of UPDRS Part I-III |  | Baseline and weeks 2, 4, 6, 8, 10, 12 | 
| Change from baseline in total score of UPDRS Part I-IV |  | Baseline and weeks 2, 4, 6, 8, 10, 12 | 
| Change from baseline in Modified Hoehn & Yahr stage |  | Baseline and weeks 2, 4, 6, 8, 10, 12 | 
| Clinical global impression of efficacy |  | week 12 | 
| Number of patients with adverse events |  | up to 16 weeks | 
| Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate) |  | up to 12 weeks | 
| Number of patients with abnormal changes in laboratory parameters |  | up to 12 weeks | 
| Number of patients with abnormal changes in 12-lead electrocardiogram (ECG) |  | up to 12 weeks |