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

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

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.

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.

Intervention(s) in this Clinical Trial

• Drug: levodopa/carbidopa
  • intestinal gel, continuous infusion (daytime or 24-hour)
• Drug: entacapone
  • Tablet, 200 mg, given twice during the study at t=0h and t=5hrs
• Drug: tolcapone
  • Tablet, 100 mg, given twice during study, at t=0h and t=5hrs.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1. Duodopa, optimised dose
• Experimental: 2. 80% Duodopa + entacapone
  • 80% of optimised Duodopa dose + two tablets of entacapone at t=0 hours and at t= 6 hours
• Experimental: 3. 80% Duodopa + tolcapone
  • 80% of optimised Duodopa dose + two tablets of tolcapone at t=0 hours and at t= 6 hours

Primary 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
    Safety Issue?: No

Secondary Measures

• Difference in Treatment Response Scale between the treatments.
  • Time Frame: 3 days
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Uppsala University Other

Overall Clinical Trial Officials and Contacts

Dag Nyholm, MD, PhD Principal Investigator Uppsala University  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00906828

Study ID Number: DuoCOMT

ClinicalTrials.gov Identifier: NCT00906828

Health Authority: Sweden: Medical Products Agency