E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061536 |
E.1.2 | Term | Parkinson's disease |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
To compare the effects of Stalevo 200 and Sinemet on levodopa mean concentrations between 2.5 – 3.5 h (C2.5-3.5). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
|
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | 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 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 8 |