An Exploratory Study of XP21279 (With Lodosyn®) and Sinemet® in Parkinson's Disease Subjects

Study Overview
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Brief Summary
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The purpose of the study is to assess the pharmacokinetics, pharmacodynamics, and safety of XP21279 sustained release formulation [administered with Lodosyn® (carbidopa)] and Sinemet® tablets in subjects with Parkinson's disease with Motor Fluctuations.

Detailed Description
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This is a Phase 1/Phase 2 multiple-dose, multi-center, open-label, two period sequential-treatment study in subjects with Parkinson's disease to assess the pharmacokinetics, pharmacodynamics, and safety of XP21279 sustained release formulation [administered with Lodosyn® (carbidopa)] and Sinemet® tablets in subjects with Parkinson's disease and to explore dose correspondence between XP21279 and Sinemet® to guide dose selection for future studies in the target population (subjects with Parkinson's disease with motor fluctuations on Sinemet®).

Official Title
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An Exploratory Pharmacokinetic, Pharmacodynamic and Safety Study of XP21279 (With Lodosyn®) and Sinemet® in Parkinson's Disease Subjects With Motor Fluctuations

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Sinemet 25-100 Oral Tablet
* Drug: XP21279
* Drug: Carbidopa Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a clinical diagnosis of idiopathic Parkinson's disease, confirmed by the presence of at least two cardinal signs of the disease (resting tremor, bradykinesia, rigidity). Subjects must have predictable motor fluctuations of the wearing off type, defined by wearing off in at least 50% of inter-dose intervals between the first and the last daily doses as recorded on the on/off diary over 3 days (Days -4 to -2) in the Screening Period. Subjects must be on stable TID or QID Sinemet® or carbidopa/levodopa regimens from morning through early evening, with a total daily dose ranging from 400 mg to 1000 mg of levodopa, for at least 1 week prior to Screening. Exclusion Criteria: History, signs, or symptoms suggesting the diagnosis of secondary or atypical Parkinsonism. Subject has greater than or equal to moderately disabling dyskinesias for greater than 25% of the waking day as assessed by a score of 2 or more on item 32 and a score of 2 or more on item 33 on the UPDRS at Screening. Subjects who are dosing with Sinemet® or carbidopa/levodopa during the night time. Subjects who have significant neurological symptoms not accounted for by Parkinson's disease. Subjects who are taking concomitantly COMT inhibitors (i.e., entacapone or tolcapone) or treated with Stalevo®, Sinemet® CR, or Madopar®/Prolopa® (levodopa/benserazide).

Ages Eligible for Study
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Minimum Age: 30 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Period A<br>Treatment Period A: Sinemet® 25-100 treatment After screening all subjects will be placed on a fixed dosing Sinemet® time regimen for approximately 14 days. | Drug: Sinemet 25-100 Oral Tablet<br>* After screening all subjects will be placed on a fixed dosing Sinemet® time regimen for approximately 14 days.<br>* Other names: Carbidopa / Levodopa;|
| Experimental: Treatment Period B<br>Multiple-Dose XP21279 (with Lodosyn®) treatment. Upon completion of Sinemet® treatment eligible subjects will be placed on a fixed dosing time regimen of XP21279 (with Lodosyn®). | Drug: XP21279<br>* Upon completion of Sinemet® treatment eligible subjects will be placed on a fixed dosing time regimen of XP21279 (with Lodosyn®).<br>* Other names: XP21279 sustained related;Drug: Carbidopa Pill<br> <br> * Other names: Lodosyn;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to assess the pharmacokinetics of XP21279 sustained release formulation [administered with Lodosyn® (carbidopa)] and Sinemet® tablets in subjects with Parkinson's disease. | To establish a pharmacokinetic profile for XP21279 | 4 weeks | 
| to assess the Pharmacodynamics of XP21279 sustained release formulation [administered with Lodosyn® (carbidopa)] and Sinemet® tablets in subjects with Parkinson's disease. | Changes in The Brief Parkinsonism Rating Scale during treatment | 4 weeks | 
| to assess the safety of XP21279 sustained release formulation [administered with Lodosyn® (carbidopa)] and Sinemet® tablets in subjects with Parkinson's disease. | Observe values and changes in clinical laboratory and vital sign parameters describe by time of collection for each treatment period. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the dose correspondence between XP21279 and Sinemet® will be explored to guide dose selection for future studies in the target population | comparison of PK levels and doses. | 4 weeks |