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

Phase 1

Completed

Interventions: Drug: Sinemet 25-100 Oral Tablet
Drug: XP21279
Drug: Carbidopa Pill

Brief Summary: 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: 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®).

Recruitment & Eligibility

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).

Arm && Interventions

Group	Intervention	Description
Treatment Period A	Sinemet 25-100 Oral Tablet	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.
Treatment Period B	XP21279	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®).
Treatment Period B	Carbidopa Pill	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®).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
the dose correspondence between XP21279 and Sinemet® will be explored to guide dose selection for future studies in the target population	4 weeks	comparison of PK levels and doses.