A Phase 3 Study With P2B001 in Subjects With Early Parkinson's

Study Overview
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Brief Summary
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P2B001 is an investigational drug that comprised of low doses of two drugs, pramipexole and rasagiline, which are both approved drugs and routinely used in standard therapy for Parkinson's disease. The two drugs work in two different mechanisms that help each other, so there is a reason to believe that their combined activity will be better than each individual drug, and that lower doses can be used without losing the therapeutic effect. Thus, the development of P2B001 is intended to provide a combination of low doses of these two drugs, in an improved formulation, that is hoped to be more effective in controlling Parkinson's disease symptoms and with less side effects than each of the drugs taken alone or the current available commercial drugs taken together. In a previously completed clinical trial a significant improvement in Parkinson's disease symptoms was seen in patients treated with P2B001 compared to patients that were treated with placebo. In this phase 3 study , the safety and efficacy of P2B001 will be assessed by comparing P2B001 to its individual components pramipexole and rasagiline. This will be done by monitoring the motor and non-motor symptoms, evaluating responses participants provide on questionnaires relating to Parkinson's disease and quality of life that will be completed on every visit. In addition, this study will also compare P2B001 to a marketed drug of pramipexole ER. Approximately 525 patients will participate in this research study and the participation in this study will last between 14 to 18 weeks.

Detailed Description
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A total of 525 eligible subjects with early untreated Parkinson's disease (PD), will be randomized to 4 treatment groups. Each subject will participate in the study for approximately 18 weeks including a 30 day screening period, 12 week treatment period, and 2 weeks follow-up period. Subjects will be requested to take one capsule and 1-3 tablets of study drug by mouth with a glass of water every day for 13 weeks. The study requires seven visits to the clinic one every 2-4 weeks.

Official Title
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A Phase 3, Twelve-week Study to Determine the Efficacy, Safety and Tolerability of P2B001 Once Daily Compared to Its Individual Components in Subjects With Early Parkinson's Disease and to a Calibration Arm of Pramipexole ER.

Conditions
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Parkinson Disease, Early Parkinson's Disease

Intervention / Treatment
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* Drug: P2B001 0.6/0.75 mg
* Drug: Rasagiline 0.75 mg
* Drug: Pramipexole 0.6 mg
* Drug: Marketed Pramipexole ER


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has Parkinson's disease consistent with the UK Brain Bank Criteria and must have bradykinesia with sequence effect. If rest tremor does not exist must have prominent asymmetry of motor function. Subject with disease duration less than 3 years since diagnosis. Subject has a H&Y stage score of < 3. Subject has a MMSE score ≥ 26. Exclusion Criteria: Subject has an atypical parkinsonian syndrome or secondary parkinsonism 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 has taken anticholinergic drugs for PD or amantadine for longer than 4 weeks; if previous exposure was less than 4 weeks then it must not be within 1 month prior to the baseline visit. Subject has moderate (Child-Pugh categorization B, score 7-9) or severe (Child-Pugh categorization C, score 10-15) hepatic impairment.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 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
Interventional Model Description: 4 arms
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P2B001 0.6/0.75 mg<br>Fixed dose combination once daily capsule of pramipexole 0.6mg and rasagiline 0.75mg, + matching placebo tablet | Drug: P2B001 0.6/0.75 mg<br>* Fixed low dose extended release combination capsule of pramipexole and rasagiline<br>* Other names: P2B001 capsule;|
| Experimental: rasagiline 0.75mg<br>Rasagiline 0.75mg Once daily capsule, component of P2B001, + matching placebo tablet | Drug: Rasagiline 0.75 mg<br>* Rasagiline 0.75 mg oral extended release capsule, component<br>* Other names: RAS 0.75;|
| Experimental: Pramipexole 0.6mg<br>Pramipexole 0.6mg once daily capsule, component of P2B001 + matching placebo tablet | Drug: Pramipexole 0.6 mg<br>* Pramipexole 0.6 mg oral extended release capsule, component<br>* Other names: PPX 0.6;|
| Active Comparator: Pramipexole Extended Release<br>Marketed pramipexole ER tablet titrated to optimal dose of 1.5, 3.0 or 4.5mg + matching placebo capsule | Drug: Marketed Pramipexole ER<br>* Marketed Pramipexole ER titrated to optimal dose of 1.5, 3 or 4.5 mg tablet<br>* Other names: PramiER;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score (Defined as Sum of Parts II and III, Scores (0-160). | Differences between P2B 0.6/0.75 mg as compared to its individual components in the change of total UPDRS score (defined as sum of parts II and III, scores (0-160). UPDRS- Unified Parkinson's Disease Rating Scale, minimum value is 0 points and maximum value is 160. High score mean worse outcome. | baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Epworth Sleepiness Scale (ESS) Score. | Differences between P2B 0.6/0.75 mg as compared to pramipexole ER tablets in the change of Epworth Sleepiness Scale (ESS) score. Scale is 0-24 , when 24 is worse outcome | baseline to week 12 | 
| Change From Baseline to Week 12 in Total UPDRS III Motor | Differences between P2B 0.6/0.75 mg as compared to its individual components in the change of Motor UPDRS score (UPDRS Part III ). UPDRS- Unified Parkinson's Disease Rating Scale, part III motor . min is 0 and Max is 108 (Worse outcome) | baseline to week 12 | 
| Change From Baseline to Week 12 in Total UPDRS II ADL | Differences between of P2B 0.6/0.75 mg as compared to its individual components in the change of ADL UPDRS score (UPDRS part II) Activity of daily Life UPDRS part II minimum is 0 point and max is 52 point (worse outcome) | Baseline to week 12 | 
| Change From Baseline to End of Week 12 Visit in ADL Subscale of PDQ39 | The efficacy of P2B 0.6/0.75 mg as compared to Pramipexole ER tablet titrated to optimal dose. ADL PDQ39- Activity of daily life part in Parkinson's Disease Questionaries' 39 Score 0-100 when 100 is the worse outcome | Baseline to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson disease, early Parkinson's Disease, Parkinson's diagnosis, Parkinson's tretment, Parkinson's medications