Safety, Tolerability and Efficacy of Two Doses of Once Daily P2B001 in Subjects With Early Parkinson's Disease

Study Overview
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Brief Summary
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This study will evaluate an oral fixed-dose, once daily product that combines pramipexole and rasagiline for the treatment of early Parkinson's disease. Animal studies support the therapeutic advantage of combining low doses of rasagiline and pramipexole and suggest further improvement when both are administered in a sustained fashion. Both rasagiline and pramipexole are well known marketed drugs for Parkinson's disease with a good safety profile. combining the drugs in low doses and controlled release may provide better symptom management than the existing drugs alone or together.

Official Title
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A Phase 2B, Twelve-week Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study, To Determine the Safety, Tolerability and Efficacy of Two Doses of Once Daily P2B001 in Subjects With Early Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: P2B001 once daily (pramipexole 0.6 mg / rasagiline 0.75 mg),
* Drug: Placebo
* Drug: P2B001 once daily (pramipexole 0.3 mg / rasagiline 0.75 mg),


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is male or female ≥35 years of age to ≤75 years of age at the time of enrollment. Subject has idiopathic Parkinson's disease consistent with the UK Brain Bank Criteria; must have bradykinesia with sequence effect and rest tremor or prominent motor asymmetry. Subject with disease duration no longer than 3 years and 0 months. Subject has a Hoehn & Yahr (H&Y) stage score of < 3. Subject has a MMSE score ≥ 26 Exclusion Criteria: Subject has an atypical parkinsonian syndrome or secondary parkinsonism (e.g., due to drugs, metabolic neurogenetic disorders, encephalitis, cerebrovascular disease or degenerative disease). Subject has a history of psychosis or hallucinations within the previous 12 months. Subject who is taking anticholinergic drugs. Subject has previous exposure to levodopa or a dopamine agonist for longer than 4 weeks; if previous exposure was less than 4 weeks then it must not be within 2 months prior to the baseline visit. Subject has previous exposure to a MAO-B inhibitor for longer than 4 weeks; if previous exposure was less than 4 weeks then it must not be within 3 months prior to the baseline visit. Subject who is taking MAO inhibitors, potent CYP1A2 inhibitors, e,g, Ciprofloxacin, Dextromethorphan or antitussive agent, analgesic agents such as tramadol, meperidine, methadone and propoxyphene, strong 3A4 inducers, e.g., St. John's Wort or cyclobenzaprine (tricyclic muscle relaxant), dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide. Probenecid, cimetidine, ranitidine, diltiazem, verapamil and quinidine.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P2B001 once daily (pramipexole 0.6 mg / rasagiline 0.75 mg),<br>Fixed Dose Combination of pramipexole 0.6 mg and rasagiline 0.75 mg once daily. | Drug: P2B001 once daily (pramipexole 0.6 mg / rasagiline 0.75 mg),<br>* Fixed Dose Combination of pramipexole 0.6 mg and rasagiline 0.75 mg once daily<br>|
| Experimental: P2B001 once daily (pramipexole 0.3 mg / rasagiline 0.75 mg),<br>Fixed Dose Combination of pramipexole 0.3 mg and rasagiline 0.75 mg once daily | Drug: P2B001 once daily (pramipexole 0.3 mg / rasagiline 0.75 mg),<br>* Fixed Dose Combination of pramipexole 0.3 mg and rasagiline 0.75 mg once daily<br>|
| Placebo Comparator: Placebo<br>Placebo once daily for 12 weeks. | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total UPDRS I, II, III Scores | Change from baseline to final visit (week 12) in total UPDRS score (defined as sum of parts I, II and III, scores (0-176). UPDRS- Unified Parkinson's Disease Rating Scale, minimum value is 0 points and maximum value is 176. High score mean worse outcome. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UPDRS ADL (Part II) | Change from baseline in individual UPDRS ADL (part II). Activity of daily Life UPDRS part II minimum is 0 point and max is 52 point (worse outcome) | Week 12 | 
| CGI-S | Change from baseline in individual Clinical Global Impression - Severity. Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness (Parkinson's Disease) at the time of assessment relative to the clinician's past experience with patients who have the same diagnosis as one of the following:. 1 is normal and 7 is the most extremely ill patients. A subject defined as a treatment responder when the improvement from baseline to the Week12 / Last Observed Value (LOV) was of at least 1 point or more. | 12 weeks | 
| UPDRS Motor (Part III) | Change from baseline in individual UPDRS motor (part III). UPDRS- Unified Parkinson's Disease Rating Scale, part III motor . min is 0 and Max is 108 (Worse outcome) | 12 weeks | 
| PDQ39 | Change from baseline in individual Parkinson's Disease Questionnaire - 39. Score 0-100 where 0 is indicative of no problem at all and 100 is the maximum level of problem. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's Disease, Rasagiline, Pramipexole