Overnight Switch Trial From Pramipexole IR to Pramipexole ER in Patients With Early Parkinson Disease

Study Overview
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Brief Summary
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The objectives of this trial conducted in early Parkinson's disease (PD) patients are: To assess if patients with early Parkinson's disease (PD) can be successfully switched (overnight switching) from Pramipexole (PPX) Immediate Release (IR) to Pramipexole Extended Release (ER). A successful switch at a specific visit is defined as no worsening of the Unified Parkinsons Disease Rating Scale (UPDRS) parts II+III score by more than 15% from baseline and no drug-related adverse events leading to withdrawal; To establish if this successful switch can be obtained with or without dose-adaptation; To provide information about the conversion ratio (mg:mg) from Pramipexole IR to Pramipexole ER.

Official Title
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A Double-blind, Double-dummy, Randomized, Parallel Groups Study to Assess the Efficacy, Safety and Tolerability of Switching Patients With Early Parkinson's Disease (PD) From Pramipexole IR to Pramipexole ER or Pramipexole IR

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Pramipexole Extended Release
* Drug: Pramipexole Immediate Release


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient with idiopathic Parkinson's disease (PD) confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity. Parkinson's disease diagnosed within 5 years. Patients 30 years of age or older at the time of diagnosis. Modified Hoehn and Yahr stage of 1 to 3. Patients receiving pramipexole IR for at least three months prior to baseline visit (randomization visit, V2). Pramipexole dose should be optimized (according investigator¿s judgement), greater or equal to 1.5 mg/day, stable and equally divided 3 times per day, for a least 4 weeks prior to baseline visit (V2). Patients willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. Signed informed consent obtained before any study procedures are carried out in accordance with International Conference on Harmonization - Good Clinical Practice (ICH-GCP) guidelines and local legislation). Exclusion Criteria: Motor complications under levodopa therapy at V1. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases. Dementia, as defined by a Mini-Mental State Exam score < 24 at V1 Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria History of psychosis, except history of drug induced hallucinations Clinically significant electrocardiogram (ECG) abnormalities at V1. Clinically significant hypotension either at screening visit or at baseline visit. Malignant melanoma or history of previously treated malignant melanoma. Any other clinically significant disease Pregnancy or breast-feeding. Sexually active female of childbearing potential Serum levels of Aspartate Aminotransferase (Serum Glutamic Oxaloacetic Transaminase) (AST (SGOT)), Alanine Aminotransferase (Serum Glutamate Pyruvate Transaminase) (ALT (SGPT)), alkaline phosphatases or bilirubin > 2 Upper Limit of Normal (ULN) (on screening lab test). Patients with a creatinine clearance < 50 mL/min Any dopamine agonist (except pramipexole IR) within three months prior to baseline visit. History of discontinuation of treatment with pramipexole IR Previous treatment with pramipexole ER. Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit (i.e. typical neuroleptics, atypical antipsychotics, reserpine, methyldopa, centrally-active antiemetics, etc). Any of the following drugs within 4 weeks prior to the baseline visit: methylphenidate, cinnarizine, amphetamines. Flunarizine within 3 months prior to baseline visit. Known hypersensitivity to Pramipexole or its excipients. Drug abuse (including alcohol), according to Investigator¿s judgement, within 2 years prior to screening. Participation in other investigational drug studies or use of other investigational drugs within 4 weeks or five times the half-life of the investigational drug (whichever is longer) prior to baseline visit.

Ages Eligible for Study
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Minimum Age: 30 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: Pramipexole Extended Release (ER)<br>Pramipexole Extended Release (ER) once daily | Drug: Pramipexole Extended Release<br> <br> |
| Experimental: Pramipexole Immediate Release (IR)<br>Pramipexole Immediate Release (IR) once daily | Drug: Pramipexole Immediate Release<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Successfully Switched From Pramipexole Immediate Release (IR) to Pramipexole ER After a Possible Dose Adaptation, Full Analysis Set (FAS), Last Observation Carried Forward (LOCF) | A successful switch was defined by no change of the Unified Parkinson's Disease Rating Scale (UPDRS) II+III by more than 15% from baseline to week 9, UPDRS II+III score ranging from 0 (no impairment) to 160 (worst impairment) | from baseline to week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Successfully Switched From Pramipexole IR to Pramipexole ER With no Dose Adaptation, FAS (LOCF) | A successful switch was defined by no change of the UPDRS II+III by more than 15% from baseline to week 4, UPDRS II+III score ranging from 0 (no impairment) to 160 (worst impairment). | from baseline to week 4 | 
| Change From Baseline in UPDRS Part II+III Total Score at Week 9, FAS (LOCF) | Unified Parkinson's Disease Rating Scale part II+III total score on FAS, Week 9 - baseline, UPDRS II+III score ranging from 0 (no impairment) to 160 (worst impairment) | Baseline and week 9 | 
| Change From Baseline in UPDRS Part II Total Score at Week 9, FAS (LOCF) | Unified Parkinson's Disease Rating Scale part II total score on FAS, Week 9 - baseline, UPDRS II score ranging from 0 (no impairment) to 52 (worst impairment) | Baseline and week 9 | 
| Change From Baseline in UPDRS Part III Total Score at Week 9, FAS (LOCF) | Unified Parkinson's Disease Rating Scale part III total score on FAS, week 9 - baseline, UPDRS II+III score ranging from 0 (no impairment) to 108 (worst impairment) | Baseline and week 9 | 
| Clinical Global Impression - Improvement (CGI-I), FAS (LOCF) | Clinical Global Impression - Improvement on FAS, CGI-I was rated from 1: very much improved, to 7: very much worse, CGI-I responder are defined as being rated as 'unchanged', 'minimally improved', 'much improved', or 'very much improved', CGI-I non-responder are defined as being rated 'minimally worse', 'much worse' or 'very much worse' | Week 9 | 
| Patient Global Impression - Improvement (PGI-I), FAS (LOCF) | Patient Global Impression - Improvement on FAS, PGI-I was rated from 1: very much better, to 7: very much worse, PGI-I responder are defined as being rated as 'unchanged', 'minimally better', 'much better', or 'very much better', PGI-I non-responder are defined as being rated as 'minimally worse', 'much worse', or 'very much worse' | Week 9 | 
| Pramipexole Dose Adaptation, FAS (LOCF) | Patients with increase in daily Pramipexole dose on FAS | Week 9 | 
| Final Pramipexole Dose (mg) After 9 Weeks, Treated Set | The mean final daily Pramipexole dose is displayed | Week 9 |