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

This study has been completed.
Sponsor:
Collaborators:
Swedish Parkinson's Disease Foundation
Swedish Society for Medical Research
Information provided by:
Uppsala University
ClinicalTrials.gov Identifier:
NCT00906828
First received: May 19, 2009
Last updated: January 15, 2010
Last verified: January 2010
  Purpose

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 Intervention Phase
Parkinson Disease
Drug: levodopa/carbidopa
Drug: entacapone
Drug: tolcapone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (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

Resource links provided by NLM:


Further study details as provided by Uppsala University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Difference in Treatment Response Scale between the treatments. [ Time Frame: 3 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: October 2008
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   30 Years to 90 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00906828

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

Publications:
Responsible Party: Dag Nyholm, MD, PhD, Uppsala University
ClinicalTrials.gov Identifier: NCT00906828     History of Changes
Other Study ID Numbers: DuoCOMT
Study First Received: May 19, 2009
Last Updated: January 15, 2010
Health Authority: Sweden: Medical Products Agency

Keywords provided by Uppsala University:
Levodopa/carbidopa infusion
entacapone
tolcapone
efficacy
pharmacokinetic
pharmacodynamics

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Carbidopa
Levodopa
Tolcapone
Entacapone
Carbidopa, levodopa drug combination
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Dopamine Agonists
Adjuvants, Immunologic
Immunologic Factors

ClinicalTrials.gov processed this record on July 23, 2014