Effects of single doses of Stalevo 200 and levodopa/carbidopa 200/50 mg on striatal 11C-raclopride binding potential in Parkinson’s disease patients with wearing-off symptoms. An open, randomised, active-controlled, two-period crossover study.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-002496-14-FI
• Date of registration: 14/09/2007
• Prospective Registration: Yes
• Primary sponsor: Orion Corporation Orion Pharma
• Public title: Effects of single doses of Stalevo 200 and levodopa/carbidopa 200/50 mg on striatal 11C-raclopride binding potential in Parkinson’s disease patients with wearing-off symptoms. An open, randomised, active-controlled, two-period crossover study.
• Scientific title: Effects of single doses of Stalevo 200 and levodopa/carbidopa 200/50 mg on striatal 11C-raclopride binding potential in Parkinson’s disease patients with wearing-off symptoms. An open, randomised, active-controlled, two-period crossover study.
• Date of first enrolment: 05/11/2007
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002496-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Finland

Key inclusion & exclusion 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/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 (IC) obtained.
8. Age of 45-80 years, inclusive.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 MRI or 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 ECG finding with clinical relevance.
11. Female patients of childbearing potential (menstruating or less than 2 years postmenopausal) 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson’s disease
MedDRA version: 9.1 Level: LLT Classification code 10061536 Term: Parkinson's disease

Intervention(s)

Product Name: Stalevo®
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Levodopa
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: Carbidopa
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Entacapone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Sinemet®
Pharmaceutical Form: Tablet
INN or Proposed INN: Levodopa
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Carbidopa
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Name: 11C-Raclopride
Pharmaceutical Form: Solution for injection
Other descriptive name: 11C-Raclopride
Concentration unit: Sv sievert
Concentration type: equal
Concentration number: 0.0017-

Primary Outcome(s)

Main Objective: To compare the effect of Stalevo 200 and Sinemet on the change of striatal (butaminal and caudate) 11C-raclopride binding potential (BP) from baseline in PD patients with wearing-off symptoms.

Secondary Objective: To compare the effects of Stalevo 200 and Sinemet on levodopa mean concentrations between 2.5 – 3.5 h (C2.5-3.5).

Primary end point(s): The effect of Stalevo 200 and Sinemet on the change of striatal (butaminal and caudate) 11C-raclopride BP from the baseline

Secondary ID(s)

2939121