Study of (Mirapex) Pramipexole for the Early Treatment of Parkinsons Disease (PD)

Study Overview
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Brief Summary
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This is a double blind, placebo-controlled clinical trial of 15 months duration designed to examine early Mirapex (pramipexole) treatment vs. delayed Mirapex (pramipexole) treatment in patients with new onset Parkinsons disease

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group Clinical Trial to Examine the Efficacy and Safety of Early Pramipexole (PPX) Treatment Versus Delayed Pramipexole Treatment in Patients With New Onset Parkinson's Disease.

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: pramipexole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide written informed consent in accordance with Good Clinical Practice (GCP) and local legislation; Male or female patient with idiopathic Parkinson Disease (PD) confirmed by at least three of the following signs: resting tremor, bradykinesia, rigidity, and asymmetry (must have bradykinesia); Parkinsons disease newly diagnosed within the past 2 years; Patients with idiopathic PD characterized as Stage I-II by the Modified Hoehn and Yahr Scale who do not require PD medication and will not likely need PD medication for at least 6 months in the opinion of the investigator; Age 30 to 75 years at screening (Visit 1); Women of childbearing potential must have a negative serum Beta-HumanChorionGonadotropin (Beta-HCG) pregnancy test at the Screening (Baseline) visit unless surgically sterile or post-menopausal (last menstruation 12 months prior to signing Informed Consent). Women of childbearing potential must be using a medically accepted contraceptive method. Acceptable methods of birth control are limited to: Intra-Uterine Device (IUD), oral, implantable, or injectable contraceptives, estrogen patch, and double barrier method (spermicide + diaphragm); and Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Previous history of allergic response or complications with pramipexole (PPX) or its excipients; Atypical PD syndromes due to either drugs (e.g., metoclopramide, flunarizine) or metabolic disorders (e.g., Wilsons Disease), encephalitis, or degenerative diseases (e.g., progressive supranuclear palsy); The patient is currently on L-dopa, dopamine agonists or other PD medication at baseline; The patient has been on L-dopa, dopamine agonists or other PD medications for greater than 14 consecutive days prior to baseline; If on L-dopa, dopamine agonists or other PD medications prior to baseline, the patient stopped treatment less than 30 days prior to baseline; The patient has clinically significant abnormal laboratory values, and/or medical or psychiatric illness other than as seen in Parkinsons disease; The patient has a clinically significant deviation from normal in the physical examination other than as seen in Parkinsons disease; The patient has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery); History of stereotactic brain surgery; Surgery within 6 months of randomization, which in the opinion of the investigator, would negatively impact the patients participation in the study; History of active epilepsy (i.e., occurrence of a seizure) within the past year; Symptomatic orthostatic hypotension prior to randomization; Malignant melanoma or history of previously treated malignant melanoma; Patients who have received any of the following drugs (all time periods are calculated from randomization): Amantadine; Electroconvulsive therapy during 180 days preceding the screening visit (Visit 1); Patients who are currently pregnant or planning pregnancy during the study, or lactating; Participation in other investigational drug studies or use of other investigational drugs within the previous 30 days prior to randomization; History of psychosis; A diagnosis of dementia

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 79 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Pramipexole<br>Patients were treated with pramipexole for 6 to 9 months then up-titrated to target dose of pramipexole (2.25 mg/day). | Drug: pramipexole<br> <br> |
| Experimental: Delayed Pramipexole<br>Patients were treated with placebo for 6 to 9 months then up-titrated to target dose of pramipexole (2.25 mg/day). | Drug: pramipexole<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Blinded Rater Unified Parkinson's Disease Rating Scale (UPDRS) Total Score at Month 15 | The UPDRS total score (Parts I+II+III) measures the impact of PD on mentation, behaviour and mood, activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 176 (worst disability) | Baseline and Month 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Investigator Rated UPDRS Total Score at Month 15 | The UPDRS total score (Parts I+II+III) measures the impact of PD on mentation, behaviour and mood, activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 176 (worst disability) | Baseline and Month 15 | 
| Change From Baseline in the Investigator Rated UPDRS Total Score at Month 9 | The UPDRS total score (Parts I+II+III) measures the impact of PD on mentation, behaviour and mood, activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 176 (worst disability) | Baseline and Month 9 | 
| Change From Baseline in the Investigator Rated UPDRS Total Score at Month 6 | The UPDRS total score (Parts I+II+III) measures the impact of PD on mentation, behaviour and mood, activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 176 (worst disability) | Baseline and Month 6 | 
| Change From Baseline in the Investigator Rated UPDRS Total Score at Month 3 | The UPDRS total score (Parts I+II+III) measures the impact of PD on mentation, behaviour and mood, activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 176 (worst disability) | Baseline and Month 3 | 
| Change From Baseline in the Blinded Rater UPDRS Parts II+III Total Score at Month 15 | The UPDRS Parts II+III total score measures the impact of PD on activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 160 (worst disability) | Baseline and Month 15 | 
| Change From Baseline in the Investigator Rated UPDRS Parts II+III Score at Month 15 | The UPDRS Parts II+III total score measures the impact of PD on activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 160 (worst disability) | Baseline and Month 15 | 
| Change From Baseline in the Investigator Rated UPDRS Parts II+III Score at Month 9 | The UPDRS Parts II+III total score measures the impact of PD on activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 160 (worst disability) | Baseline and Month 9 | 
| Change From Baseline in the Investigator Rated UPDRS Parts II+III Score at Month 6 | The UPDRS Parts II+III total score measures the impact of PD on activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 160 (worst disability) | Baseline and Month 6 | 
| Change From Baseline in the Investigator Rated UPDRS Parts II+III Score at Month 3 | The UPDRS Parts II+III total score measures the impact of PD on activities of daily living and motor skills on an ordinal scale ranging from 0 (no disability) to 160 (worst disability) | Baseline and Month 3 | 
| Change From Baseline in the Blinded Rater UPDRS Part III Total Score at Month 15 | The UPDRS Part III total score measures the impact of PD on motor skills on an ordinal scale ranging from 0 (no disability) to 108 (worst disability) | Baseline and Month 15 | 
| Change From Baseline in the Investigator Rated UPDRS Part III Score at Month 15 | The UPDRS Part III total score measures the impact of PD on motor skills on an ordinal scale ranging from 0 (no disability) to 108 (worst disability) | Baseline and Month 15 | 
| Change From Baseline in the Investigator Rated UPDRS Part III Score at Month 9 | The UPDRS Part III total score measures the impact of PD on motor skills on an ordinal scale ranging from 0 (no disability) to 108 (worst disability) | Baseline and Month 9 | 
| Change From Baseline in the Investigator Rated UPDRS Part III Score at Month 6 | The UPDRS Part III total score measures the impact of PD on motor skills on an ordinal scale ranging from 0 (no disability) to 108 (worst disability) | Baseline and Month 6 | 
| Change From Baseline in the Investigator Rated UPDRS Part III Score at Month 3 | The UPDRS Part III total score measures the impact of PD on motor skills on an ordinal scale ranging from 0 (no disability) to 108 (worst disability) | Baseline and Month 3 | 
| Change From Baseline in the Blinded Rater UPDRS Part II Total Score at Month 15 | The UPDRS Part II total score measures the impact of PD on activities of daily living on an ordinal scale ranging from 0 (no disability) to 52 (worst disability) | Baseline and Month 15 | 
| Change From Baseline in the Investigator Rated UPDRS Part II Score at Month 15 | The UPDRS Part II total score measures the impact of PD on activities of daily living on an ordinal scale ranging from 0 (no disability) to 52 (worst disability) | Baseline and Month 15 | 
| Change From Baseline in the Investigator Rated UPDRS Part II Score at Month 9 | The UPDRS Part II total score measures the impact of PD on activities of daily living on an ordinal scale ranging from 0 (no disability) to 52 (worst disability) | Baseline and Month 9 | 
| Change From Baseline in the Investigator Rated UPDRS Part II Score at Month 6 | The UPDRS Part II total score measures the impact of PD on activities of daily living on an ordinal scale ranging from 0 (no disability) to 52 (worst disability) | Baseline and Month 6 | 
| Change From Baseline in the Investigator Rated UPDRS Part II Score at Month 3 | The UPDRS Part II total score measures the impact of PD on activities of daily living on an ordinal scale ranging from 0 (no disability) to 52 (worst disability) | Baseline and Month 3 | 
| Change From Baseline in the Blinded Rater UPDRS Part I Total Score at Month 15 | The UPDRS Part I total score measures the impact of PD on mentation, behaviour and mood on an ordinal scale ranging from 0 (no disability) to 16 (worst disability) | Baseline and Month 15 | 
| Change From Baseline in the Investigator Rated UPDRS Part I Total Score at Month 15 | The UPDRS Part I total score measures the impact of PD on mentation, behaviour and mood on an ordinal scale ranging from 0 (no disability) to 16 (worst disability) | Baseline and Month 15 | 
| Change From Baseline in the Investigator Rated UPDRS Part I Total Score at Month 9 | The UPDRS Part I total score measures the impact of PD on mentation, behaviour and mood on an ordinal scale ranging from 0 (no disability) to 16 (worst disability) | Baseline and Month 9 | 
| Change From Baseline in the Investigator Rated UPDRS Part I Total Score at Month 6 | The UPDRS Part I total score measures the impact of PD on mentation, behaviour and mood on an ordinal scale ranging from 0 (no disability) to 16 (worst disability) | Baseline and Month 6 | 
| Change From Baseline in the Investigator Rated UPDRS Part I Total Score at Month 3 | The UPDRS Part I total score measures the impact of PD on mentation, behaviour and mood on an ordinal scale ranging from 0 (no disability) to 16 (worst disability) | Baseline and Month 3 | 
| Number of Responders Using the Blinded Rater Assessment of Clinical Global Impressions of Global Improvement (CGI-I) Score at Month 15 | The CGI-I measures the overall improvement in the participants condition from baseline on an ordinal scale ranging from 1 (very much improved) to 7 (very much worse). Responders are defined as those patients with a CGI-I of 1 or 2. | Month 15 | 
| Change From Baseline in Blinded Rater Assessment of Clinical Global Impressions of Severity of Illness (CGI-S) Category at Month 15 | The CGI-S measures the participants severity of illness on an ordinal scale ranging from 1 (normal) to 7 (extremely ill). At Month 15 participants were categorised to 'Improved' (>1 category improvement), 'Unchanged' or 'Worsened' (>1 category worsening). | Baseline and Month 15 | 
| Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Month 15 | The BDI measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 63 (worst symptoms) | Baseline and Month 15 | 
| Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Month 9 | The BDI measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 63 (worst symptoms) | Baseline and Month 9 | 
| Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Month 6 | The BDI measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 63 (worst symptoms) | Baseline and Month 6 | 
| Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Month 3 | The BDI measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 63 (worst symptoms) | Baseline and Month 3 | 
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Overall Index Score at Month 15 | The PDQ-39 measures aspects of health in PD participants, the overall index score is the mean of the eight individual domain scores measured on a continuous scale ranging from 0 (no problem at all) to 100 (maximum level of the problem) | Baseline and Month 15 | 
| Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Overall Index Score at Month 9 | The PDQ-39 measures aspects of health in PD participants, the overall index score is the mean of the eight individual domain scores measured on a continuous scale ranging from 0 (no problem at all) to 100 (maximum level of the problem) | Baseline and Month 9 | 
| Change From Baseline in the European Quality of Life Scale (EUROQOL (EQ)-5D) Overall Index Score at Month 15 | The EQ-5D measures health status on a continuous scale ranging from 0 (dead) to 1 (full health) | Baseline and Month 15 | 
| Change From Baseline in the European Quality of Life Scale (EUROQOL (EQ)-5D) Overall Index Score at Month 9 | The EQ-5D measures health status on a continuous scale ranging from 0 (dead) to 1 (full health) | Baseline and Month 9 | 
| Change From Baseline in the European Quality of Life Visual Analogue Scale (EUROQOL (EQ) VAS) Score at Month 15 | The EQ-VAS is a self rating of current health-related quality of life measured on a continuous scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state) | Baseline and Month 15 | 
| Change From Baseline in the European Quality of Life Visual Analogue Scale (EUROQOL (EQ) VAS) Score at Month 9 | The EQ-VAS is a self rating of current health-related quality of life measured on a continuous scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state) | Baseline and Month 9 | 
| Modified Minnesota Disorders Interview (MMIDI) Risk of Gambling at Month 1 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; risk of gambling is assessed via 12 questions, a participant is considered at risk if answering 'Yes' to Q1 and 'Yes' to 5 or more of Q2 to Q12. | Month 1 | 
| Modified Minnesota Disorders Interview (MMIDI) Risk of Gambling at Month 6 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; risk of gambling is assessed via 12 questions, a participant is considered at risk if answering 'Yes' to Q1 and 'Yes' to 5 or more of Q2 to Q12. | Month 6 | 
| Modified Minnesota Disorders Interview (MMIDI) Risk of Gambling at Month 9 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; risk of gambling is assessed via 12 questions, a participant is considered at risk if answering 'Yes' to Q1 and 'Yes' to 5 or more of Q2 to Q12. | Month 9 | 
| Modified Minnesota Disorders Interview (MMIDI) Risk of Gambling at Month 12 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; risk of gambling is assessed via 12 questions, a participant is considered at risk if answering 'Yes' to Q1 and 'Yes' to 5 or more of Q2 to Q12. | Month 12 | 
| Modified Minnesota Disorders Interview (MMIDI) Risk of Gambling at Month 15 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; risk of gambling is assessed via 12 questions, a participant is considered at risk if answering 'Yes' to Q1 and 'Yes' to 5 or more of Q2 to Q12. | Month 15 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Sexual Behaviour at Month 1 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive sexual behaviour is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1 and 'Yes' to 1 or more of Q2 to Q4. | Month 1 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Sexual Behaviour at Month 6 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive sexual behaviour is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1 and 'Yes' to 1 or more of Q2 to Q4. | Month 6 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Sexual Behaviour at Month 9 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive sexual behaviour is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1 and 'Yes' to 1 or more of Q2 to Q4. | Month 9 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Sexual Behaviour at Month 12 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive sexual behaviour is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1 and 'Yes' to 1 or more of Q2 to Q4. | Month 12 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Sexual Behaviour at Month 15 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive sexual behaviour is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1 and 'Yes' to 1 or more of Q2 to Q4. | Month 15 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Buying at Month 1 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive buying is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1a and 'Yes' to 1 or more of Q2a, Q3a and Q4a. | Month 1 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Buying at Month 6 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive buying is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1a and 'Yes' to 1 or more of Q2a, Q3a and Q4a. | Month 6 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Buying at Month 9 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive buying is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1a and 'Yes' to 1 or more of Q2a, Q3a and Q4a. | Month 9 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Buying at Month 12 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive buying is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1a and 'Yes' to 1 or more of Q2a, Q3a and Q4a. | Month 12 | 
| Modified Minnesota Disorders Interview (MMIDI) for Compulsive Buying at Month 15 | The MMIDI is a semi-structured interview designed to assess impulse control disorders; compulsive buying is assessed via 4 questions, a participant is considered as being compulsive if answering 'Yes' to Q1a and 'Yes' to 1 or more of Q2a, Q3a and Q4a. | Month 15 | 
| Percentage Change From Baseline in the Striatum Uptake at Month 15 | The striatum beta-carbomethoxy-iodophenyl-tropane (beta-CIT) uptake was calculated as mean of the left and right caudate and putamen regions; measured by the Single-Photon Emission Computed Tomography (SPECT). | Baseline and Month 15 | 
| Clinically Significant Abnormalities in Clinical Laboratory Measurements - Haematology and Electrolytes |  | Baseline and Month 15 | 
| Clinically Significant Abnormalities in Clinical Laboratory Measurements - Enzymes |  | Baseline and Month 15 | 
| Clinically Significant Abnormalities in Clinical Laboratory Measurements - Substrates |  | Baseline and Month 15 | 
| Clinically Significant Abnormalities in Vital Signs |  | Baseline and Month 15 |