Study to Assess Pharmacokinetics of Accordion Pill Carbidopa-Levodopa Compared to Immediate Release Carbidopa-Levodopa in Parkinson's Disease Patients

Study Overview
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Brief Summary
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The purpose of this study is to assess the PK of AP-CD/LD given at dose of 50/500mg three times daily compared to CD/LD immediate release (Sinemet) 1.5 tablets of dose of 25/100 given 5 times per day in Parkinson's Disease patients.

Detailed Description
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An open label, non randomized crossover phase 2 study to assess the PK of AP-CD/LD given at dose of 50/500mg three times daily compared to CD/LD immediate release (Sinemet) 1.5 tablets of dose of 25/100 given 5 times per day in Parkinson's Disease patients. The study will have a screening period followed by an overnight stay in clinic where Immediate release CD/LD (Sinemet) will be administered five times, approximately every three hours. At specified intervals, blood will be drawn for PK testing. On Days 2-7, subjects will be treated at home with AP CD/LD three times/day, approximately every five hours. Day 8 will be overnight stay in clinic for PK study. AP CD/LD 500mg TID will be dispensed to subjects with specified timelines for PK assessment. Each subject will return to clinic on day 15 for a safety followup visit.

Official Title
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An Open Label Phase 2 Study to Assess the Pharmacokinetics of the Accordion Pill Carbidopa-Levodopa Compared to Immediate Release Carbidopa-Levodopa in Patients With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Accordion Pill Carbidopa/Levodopa
* Drug: Sinemet CR 25Mg-100Mg Extended-Release Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of PD consistent with UK Brain Bank Criteria Stable dose of levodopa/carbidopa IR for at least 4 weeks prior to entry; taking at least 4 doses of IR levodopa during waking hours, and total daily dose of at least 400mg prior to initial screening Stable on all anti-PD medications for 30 days prior to screening. COMT inhibitors are held prior to PK studies on day 1 through day 8 Exclusion Criteria: Atypical or secondary parkinsonism clinically significant cardiac, pulmonary, hepatic, or renal disease or other condition which contraindicates participation in judgement of investigator severe dyskinesia as assessed by PI significant cognitive impairment Clinically significant psychiatric illness in opinion of PI history of small bowel or gastric surgery (including PEG-J placement for Duopa/Duodopa) or bowel obstruction, diagnosis of small bowel narrowing, diagnosis of Crohn's disease, frequent nausea or emesis regardless of etiology, and symptomatic gastroparesis. History of GI pathology of clinical significance as determined by PI Allergy to study drug or Yellow Dye #5 (tartrazine) Unable to swallow large pills Active GERD and regular use of PPIs Women who are pregnant or nursing or are of childbearing potential who are not willing to use a medically acceptable method of contraception

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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sinemet<br>Controlled Release 25/100 | Drug: Sinemet CR 25Mg-100Mg Extended-Release Tablet<br>* 25/100 1.5 pills five times/day<br>* Other names: Sinemet CR;|
| Experimental: AP CD/LD<br> | Drug: Accordion Pill Carbidopa/Levodopa<br>* AP 50/500 TID days 2-7<br>* Other names: AP-CD/LD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variability in plasma levodopa concentration | as assessed by levodopa fluctuation index (comparison of AP-CD/LD to IR-CD/LD | Pk blood sampling to be performed time 0 and every 30 minutes for 16 hours and again at 24 hours on days 1 and 8. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variability in plasma levodopa concentration | as assessed by Coefficient of variation (CV) (comparison of AP-CD/LD to IR-CD/LD) | Pk blood sampling to be performed time 0 and every 30 minutes for 16 hours and again at 24 hours on days 1 and 8. |