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

Study Description

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Drug: levodopa/carbidopa; Drug: entacapone; Drug: tolcapone	Phase 4

Detailed Description:

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.

Study Design

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	10 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Pharmacokinetics of Levodopa in Patients With Parkinson's Disease Treated With Levodopa/Carbidopa Infusion With and Without Oral COMT Inhibitors
Study Start Date :	October 2008
Actual Primary Completion Date :	November 2009
Actual Study Completion Date :	November 2009

Arms and Interventions

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Outcome Measures

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Difference in coefficient of variation of levodopa in plasma between baseline (day 1) and each of the days on COMT inhibitors. [ Time Frame: 3 days ]

Secondary Outcome Measures :

1. Difference in Treatment Response Scale between the treatments. [ Time Frame: 3 days ]

Eligibility Criteria

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	30 Years to 90 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Sweden
Uppsala University Hospital
Uppsala, Sweden, 75646

Sponsors and Collaborators

Uppsala University

Swedish Parkinson's Disease Foundation

Swedish Society for Medical Research

Investigators

Principal Investigator:	Dag Nyholm, MD, PhD	Uppsala University

More Information

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Nyholm D. Enteral levodopa/carbidopa gel infusion for the treatment of motor fluctuations and dyskinesias in advanced Parkinson's disease. Expert Rev Neurother. 2006 Oct;6(10):1403-11. Review.

Responsible Party:	Dag Nyholm, MD, PhD, Uppsala University
ClinicalTrials.gov Identifier:	NCT00906828 History of Changes
Other Study ID Numbers:	DuoCOMT
First Posted:	May 21, 2009
Last Update Posted:	January 18, 2010
Last Verified:	January 2010

Keywords provided by Uppsala University:

Levodopa/carbidopa infusion; entacapone; tolcapone	efficacy; pharmacokinetic; pharmacodynamics

Additional relevant MeSH terms:

Entacapone; Tolcapone; Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Levodopa; Carbidopa; Carbidopa, levodopa drug combination	Catechol O-Methyltransferase Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Aromatic Amino Acid Decarboxylase Inhibitors; Enzyme Inhibitors; Adjuvants, Immunologic; Immunologic Factors; Dopamine Agonists