E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic Parkinson’s disease and end-of-dose wearing off. |
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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 |
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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 |
The primary objective of this study is to evaluate the effects of Stalevo versus immediaterelease carbidopa/levodopa on the latency of the P300 component of ERPs at the midline electrode site Cz, 4 hours post-levodopa administration (ERP4hrs) in patients with idiopathic PD. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effects of Stalevo versus immediate-release carbidopa/levodopa on the mean latency of the P300 component of ERPs at midline electrode site Cz, at ERPpre-dose and ERP1hr. 2. To evaluate the effects of Stalevo versus immediate-release carbidopa/levodopa on the mean latency of the N100 component of ERPs at midline electrode site Cz, at ERPpre-dose, ERP1hr and ERP4hrs. 3. To evaluate the plasma concentration of aldosterone (AUC post dose: 9.25 h -12.55 h). 4. To evaluate the plasma concentration of ICAM-1 (AUC post dose: 9.25 h – 12.55 h) 5. To evaluate the plasma concentration of l-dopa (AUC post dose: 9.25 h – 12.55 h) 6. plasma concentration of magnesium and other electrolytes (AUC post dose: 9.25 h – 12.55 h).
For further details please refer to the enclosed protocol. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients aged 45 to 75 years (inclusive). 2. Patients with an MMSE score of at least 25 at the screening visit. 3. Patients who experience EODWO, defined as re-emergence of PD symptoms during the waking hours, as determined by a WOQ-9 score of at least one motor symptom of wearing off. An item is considered positive when it is present and when the referring symptomatology improves with the next dose of dopaminergic medication. 4. Patients taking a stable dose of immediate-release carbidopa/levodopa for at least 4 weeks prior to randomization, at an equivalent total daily dose of levodopa between 300 to 600 mg/day. 5. Patients who, in the investigator’s judgement, are capable of satisfying the requirements of the protocol. 6. Patients who are willing and able to give written informed consent according to legal requirements. |
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E.4 | Principal exclusion criteria |
1. Diagnosis of secondary parkinsonism, atypical Parkinson’s disease, or history, signs, or symptoms suggesting these diagnoses. 2. Unstable Parkinson’s disease as determined by the investigator. 3. Disabling dyskinesia (a score of >2 on the Unified Parkinson’s Disease Rating Scale [UPDRS] question #32, or a score of >2 on UPDRS question #33). 4. Treatment with carbidopa/levodopa controlled-release or extended-release formulations (bedtime administration is acceptable). The use of controlled-release Sinemet is not allowed on the evening before the visits in which efficacy assessments occur. 5. Treatment with <3 or >4 daily doses of immediate release carbidopa/levodopa of any dose form within 4 weeks (28 days) prior to randomization (this allows combination of different strengths). 6. Patients requiring less than three levodopa/carbidopa doses per day 7. Patients who are unable to comply with the dosing requirements of the protocol, such that the first dose of study medication will be taken after the time of the first EEG and the second dose will be taken after completion of the third EEG. 8. Treatment with monoamine oxidase type A (MAO-A) inhibitors or neuroleptics, within 60 days prior to the randomization. 9. Treatment with selegiline or rasagiline within 4 weeks (28 days) prior to randomization. 10. Concomitant treatment with dopamine agonists or catechol O-methyltransferase (COMT) inhibitors within 4 weeks ( 28 days) of randomization), or at any time in the past if, in the perspective of a treating physician, the patient experienced serious or severe adverse event(s) or treatment failure that resulted in the discontinuation of treatment) 11. Current treatment with anticoagulants. Aspirin taken for health or cardiac prophylaxis will be permitted, provided that the total daily dose does not exceed 81 mg. 12. Treatment with a benzodiazepine or any sleep medication. As needed use of these medications will be permitted; however, they may not be administered during the 48 hours prior to the Week 6 or Week 12 visits. 13. Use of magnesium supplements within 4 weeks (28 days) prior to randomization. 14. Treatment with angiotensin-converting enzyme (ACE)-inhibitors within 28 days prior to randomization. 15. Treatment with oral or inhaled glucocorticoids (topical preparations are permitted) within 3 months prior to randomization.
Please refer to the enclosed protocol for a detailed description of all exclusion criterias. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the mean latency of the P300 component of the ERPs. The primary analysis time point is 4 hours post levodopa administration. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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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 | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |