PET-Study: Effects of Single Doses of Stalevo and Levodopa/Carbidopa on Striatal 11C-Raclopride Binding

This study has been terminated.
(Illogistical results found in interim evaluation.)
Sponsor:
Information provided by:
Orion Corporation, Orion Pharma
ClinicalTrials.gov Identifier:
NCT00562198
First received: November 19, 2007
Last updated: June 12, 2008
Last verified: June 2008
  Purpose

This is an open, randomised, active-controlled, 2-period crossover study comparing the effect of single doses of Stalevo 200 and Sinemet on striatal (putamenal and caudate) 11C-raclopride BP in PD patients with wearing-off symptoms. The study consists of 4 visits: a screening visit (visit 1), 2 treatment periods (period 1=visit 2, period 2=visit 3) separated by a minimum wash-out period of at least 3 days, and an end-of-study visit (visit 4). Subjects will be randomly allocated to start the period 1 with a single dose of Stalevo 200 or Sinemet. After the wash-out the study drug on period 2 will be administered according to a crossover design.


Condition Intervention Phase
Parkinson´s Disease
Drug: entacapone and carbidopa
Drug: Sinemet 200mg/50mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Single Doses of Stalevo 200 and Levodopa/Carbidopa 200/50mg on Striatal 11C-Raclopride Binding Potential in Parkinson's Disease Patients With Wearing-Off Symptoms;an Open, Randomised, Active-Controlled,Two-Period Crossover Study.

Resource links provided by NLM:


Further study details as provided by Orion Corporation, Orion Pharma:

Primary Outcome Measures:
  • The difference between the study drugs in change in striatal 11C-raclopride BP.Striatal 11C-raclopride BP will be determined with PET scans performed at baseline and from 2.5 to 3.5 h after the study drug administration. [ Time Frame: Post-dosing PET scan ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The difference between the study drugs in levodopa mean C2.5- 3.5h. [ Time Frame: C 2.5-3.5h ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: January 2008
Study Completion Date: May 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Investigational drug Stalevo 200
Drug: entacapone and carbidopa
Entacapone 200mg carbidopa 50mg
Drug: Sinemet 200mg/50mg
Sinemet 200mg/50mg once

  Eligibility

Ages Eligible for Study:   45 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients with idiopathic Parkinson's disease according to the UK Brain Bank criteria.
  2. Predictable wearing-off symptoms with a response to standard release levodopa/carbidopa (200/50 mg)during the levodopa challenge test lasting for a minimum of 1.5 h and a maximum of 4 h.
  3. The magnitude of response (peak effect) in the levodopa challenge test is at least 30%. The magnitude of response is defined to be the difference between the baseline score and the lowest UPDRS III score during the levodopa challenge test.
  4. Hoehn and Yahr stage of at least 2.0 performed during the "ON" state.
  5. Treatment with at least 4 daily doses of levodopa/dopa decarboxylase inhibitor (DDCI) (± entacapone(Comtess® or Stalevo) with total daily levodopa dose in the range of 400-1200mg.
  6. Unchanged levodopa/DDCI ± entacapone and other antiparkinsonian medication [dopamine agonists,monoamine oxidase B (MAO-B) inhibitor, amantadine and/or anticholinergics with an approved dose], if any, for at least 2 weeks prior to period I.
  7. Written informed consent obtained.
  8. Age of 45-80 years, inclusive.

Exclusion Criteria:

  1. Secondary or atypical parkinsonism.
  2. Patients with any unpredictable "OFF"-periods.
  3. Patients with moderate to severe treatment-related peak-dose dyskinesia likely to affect the quality of brain magnetic resonance image (MRI) or positron emission tomography (PET) imaging.
  4. Failure to adequately respond to the levodopa (levodopa/carbidopa 200/50 mg) challenge test with the duration of response lasting less than 1.5 h or more than 4 h.
  5. Presence of a basal ganglia lesion in the MRI image or any other factor(s) that would make MRI or PET imaging likely to be unsatisfactory.
  6. Presence of any ferromagnetic objects that would make brain MRI imaging contraindicated.
  7. Patients with a history of laboratory abnormality consistent with, or clinically significant cardiovascular,pulmonary, gastrointestinal, hepatic, renal, neurological or psychiatric disorder or any other major concurrent illness, which may influence the outcome of the study including the interpretation and usage of MRI and PET images for the study purposes.
  8. History of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis, malignant melanoma, narrow-angle glaucoma or pheochromocytoma.
  9. Severe hepatic impairment.
  10. Any abnormal electrocardiogram (ECG) finding with clinical relevance.
  11. Female patients of childbearing potential (menstruating or less than 2 years post-menopausal) if they are not using adequate contraception during the study (defined as hormonal contraception, intrauterine device or surgical sterilization) or female patients who are pregnant or lactating.
  12. Treatment with cabergoline.
  13. Concomitant treatment with apomorphine, MAO-A inhibitors or non-selective MAO inhibitors.
  14. Concomitant treatment with any drugs with antidopaminergic action (e.g. with D2 receptor blocking properties) less than two weeks or within five times the elimination half-life of a given drug prior to the first study drug administration. As an exception, the use of domperidone is allowed.
  15. Current, regular use of any iron preparation that cannot be interrupted for the duration of the study
  16. Patients who are likely to need a rescue dose of levodopa after the withdrawal from their own levodopa/DDCI ± entacapone medication prior to PET imaging.
  17. Known hypersensitivity to active study drug substances or to any of the excipients.
  18. Participation in other drug studies within 30 days prior to study entry.
  19. Blood donation or loss of significant amount of blood within 60 days prior to the screening.
  20. Any other condition that in the opinion of the investigator could create a hazard to the subject safety,endanger the study procedures or interfere with the interpretation of study results.
  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: NCT00562198

Locations
Finland
Helsinki University Hospital, Department of Neurology
Helsinki, Finland, 00029
Oulu University Hospital, Department of Neurology
Oulu, Finland, 90220
Porin Lääkäritalo
Pori, Finland, 28100
FinnMedi Tutkimus Oy
Tampere, Finland, 33520
CRST
Turku, Finland, 20520
Sponsors and Collaborators
Orion Corporation, Orion Pharma
Investigators
Principal Investigator: Juha Rinne, Dr Turku PET Centre, Turku, Finland
  More Information

No publications provided

Responsible Party: Irja Korpela, Orion Pharma
ClinicalTrials.gov Identifier: NCT00562198     History of Changes
Other Study ID Numbers: 2939121
Study First Received: November 19, 2007
Last Updated: June 12, 2008
Health Authority: Finland: Finnish Medicines Agency

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
Carbidopa, levodopa drug combination
Entacapone
Raclopride
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
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Adjuvants, Immunologic
Immunologic Factors

ClinicalTrials.gov processed this record on August 27, 2014