Pharmacokinetics of Levodopa/Carbidopa Infusion With and Without Oral Catechol-O-methyl Transferase (COMT) Inhibitors

Study Overview
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Brief Summary
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The purpose of this study is to determine whether oral intake of COMT inhibitors affects the smooth plasma levodopa levels achieved by intestinal levodopa/carbidopa infusion in advanced Parkinson's disease patients. The hypothesis is that COMT inhibitors make plasma concentrations of levodopa more fluctuating.

Detailed Description
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The aim is to measure variability in plasma levodopa levels during the following three treatments: Day 1: Duodopa in individually optimised dose Day 2: 80% of optimised Duodopa dose + two tablets of entacapone at t=0 hours and at t= 6 hours Day 3: 80% of optimised Duodopa dose + two tablets of tolcapone at t=0 hours and at t= 6 hours Plasma samples for determination of levodopa concentrations will be taken every 30 minutes during 8 hours. Video recordings will be performed every 30 min during 8 hours, for later blinded assessments by 2-3 experts. Sequences will be in randomised order. Patient self-scores regarding mobility will be recorded, every 30 min during 8 hours.

Official Title
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Pharmacokinetics of Levodopa in Patients With Parkinson's Disease Treated With Levodopa/Carbidopa Infusion With and Without Oral COMT Inhibitors

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: levodopa/carbidopa
* Drug: entacapone
* Drug: tolcapone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parkinson's disease Duodopa treatment ongoing Hoehn & Yahr stage 3-5 at worst Exclusion Criteria: Ongoing treatment with COMT inhibitors Dementia Psychosis Treatment with typical neuroleptics Contraindications for entacapone or tolcapone

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 90 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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1. Duodopa, optimised dose<br> | Drug: levodopa/carbidopa<br>* intestinal gel, continuous infusion (daytime or 24-hour)<br>* Other names: Duodopa;|
| Experimental: 2. 80% Duodopa + entacapone<br>80% of optimised Duodopa dose + two tablets of entacapone at t=0 hours and at t= 6 hours | Drug: entacapone<br>* Tablet, 200 mg, given twice during the study at t=0h and t=5hrs<br>* Other names: Comtess, Comtan.;|
| Experimental: 3. 80% Duodopa + tolcapone<br>80% of optimised Duodopa dose + two tablets of tolcapone at t=0 hours and at t= 6 hours | Drug: tolcapone<br>* Tablet, 100 mg, given twice during study, at t=0h and t=5hrs.<br>* Other names: Tasmar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in coefficient of variation of levodopa in plasma between baseline (day 1) and each of the days on COMT inhibitors. |  | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Treatment Response Scale between the treatments. |  | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Levodopa/carbidopa infusion, entacapone, tolcapone, efficacy, pharmacokinetic, pharmacodynamics