A 12-Week, Multi-center, Randomized, Prospective, Open-Label, Blinded Rater, Crossover Study of the Effects of Immediate-Release Carbidopa/Levodopa Versus Stalevo® on Markers of Event-Related Potentials (ERPs) in Patients with Idiopathic Parkinson’s Disease and End-of-Dose Wearing Off.

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2007-003134-42-DE
• Date of registration: 20/02/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 12-Week, Multi-center, Randomized, Prospective, Open-Label, Blinded Rater, Crossover Study of the Effects of Immediate-Release Carbidopa/Levodopa Versus Stalevo® on Markers of Event-Related Potentials (ERPs) in Patients with Idiopathic Parkinson’s Disease and End-of-Dose Wearing Off.
• Scientific title: A 12-Week, Multi-center, Randomized, Prospective, Open-Label, Blinded Rater, Crossover Study of the Effects of Immediate-Release Carbidopa/Levodopa Versus Stalevo® on Markers of Event-Related Potentials (ERPs) in Patients with Idiopathic Parkinson’s Disease and End-of-Dose Wearing Off.
• Date of first enrolment: 19/06/2008
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003134-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: yes Other: yes Other trial design description: blinded-rater If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

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.
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. 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.


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

Health Condition(s) or Problem(s) studied

Idiopathic Parkinson’s disease and end-of-dose wearing off.
MedDRA version: 9.1 Level: LLT Classification code 10061536 Term: Parkinson's disease

Intervention(s)

Trade Name: Stalevo 100 mg/ 25 mg/ 200 mg Filmtabletten
Product Name: Stalevo
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LEVODOPA
CAS Number: 59927
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: CARBIDOPA
CAS Number: 28860959
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: ENTACAPONE
CAS Number: 130929576
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Nacom 100
Product Name: Nacom
Pharmaceutical Form: Tablet
INN or Proposed INN: LEVODOPA
CAS Number: 59927
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: CARBIDOPA
CAS Number: 38821-49-7
Other descriptive name: CARBIDOPA MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 27-

Primary Outcome(s)

Main Objective: 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.

Secondary Objective: 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.

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.

Secondary ID(s)

CELC200AUS15