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

NCT ID: NCT00906828

Last Updated: 2010-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2009-11-30

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.

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.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

1. Duodopa, optimised dose

Group Type: ACTIVE_COMPARATOR

levodopa/carbidopa

Intervention Type: DRUG

intestinal gel, continuous infusion (daytime or 24-hour)

2. 80% Duodopa + entacapone

80% of optimised Duodopa dose + two tablets of entacapone at t=0 hours and at t= 6 hours

Group Type: EXPERIMENTAL

entacapone

Intervention Type: DRUG

Tablet, 200 mg, given twice during the study at t=0h and t=5hrs

3. 80% Duodopa + tolcapone

80% of optimised Duodopa dose + two tablets of tolcapone at t=0 hours and at t= 6 hours

Group Type: EXPERIMENTAL

tolcapone

Intervention Type: DRUG

Tablet, 100 mg, given twice during study, at t=0h and t=5hrs.

Interventions

levodopa/carbidopa

intestinal gel, continuous infusion (daytime or 24-hour)

Intervention Type: DRUG

entacapone

Tablet, 200 mg, given twice during the study at t=0h and t=5hrs

Intervention Type: DRUG

tolcapone

Tablet, 100 mg, given twice during study, at t=0h and t=5hrs.

Intervention Type: DRUG

Other Intervention Names

Duodopa; Comtess, Comtan.; Tasmar

Eligibility 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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swedish Parkinson's Disease Foundation

UNKNOWN

Sponsor Role: collaborator

Swedish Society for Medical Research

OTHER

Sponsor Role: collaborator

Uppsala University

OTHER

Sponsor Role: lead

Responsible Party

Uppsala University

Principal Investigators

Dag Nyholm, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Uppsala University

Locations

Uppsala University Hospital

Uppsala, , Sweden

Countries

Sweden

References

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. doi: 10.1586/14737175.6.10.1403.

Reference Type: BACKGROUND

PMID: 17078781 (View on PubMed)

Other Identifiers

DuoCOMT

Identifier Type: -

Identifier Source: org_study_id