Efficacy of Levodopa/Carbidopa/Entacapone vs Levodopa/Carbidopa in Parkinson's Disease Patients With Early Wearing-off

A 3-month, Multi-center, Double-blind, Randomized Study to Evaluate the Efficacy of Levodopa/Carbidopa/Entacapone vs Levodopa/Carbidopa in Parkinson's Disease Patients With Impairment of Activities of Daily Living and Early Wearing-off With Levodopa

The study evaluated the efficacy of levodopa/carbidopa/entacapone vs levodopa/carbidopa in patients with Parkinson's disease and early wearing-off with levodopa

Inclusion Criteria:

1. Male and female patients ages ≥ 30 and ≤ 80 years old.

2. A clinical diagnosis of idiopathic Parkinson's disease.

3. Taking a stable dose of levodopa/carbidopa (≥ 300 and ≤ 600mg) for a period of at least 1 month prior to study entry.

4. Must be using any of the following levodopa/carbidopa standard formulation levodopa/carbidopa 100/25mg dose in any intake of the day.

   • 1 full tablet, and/or
   • 1½ tablets The patient can also be using, for a period of at least 1 month prior to study entry, 1 tablet of the controlled release formulation of levodopa/carbidopa 100/25 mg (marketed in Spain as Sinemet Plus retard) or 1 tablet the controlled release formulation of levodopa/carbidopa 200/50 mg (marketed in Spain as Sinemet retard) in each intake, at different doses.

5. Must have early end-of-dose wearing-off defined by >= 2 or <=7 positive responses to the QUICK questionnaire.

6. Must have a minimum UPDRS part II (ADL) score of 9.

7. Patients without dyskinesia or with mild dyskinesia.

8. Female patients must be either post-menopausal or using one or more acceptable methods of contraception.

9. Must be capable of satisfying the requirements of the protocol and must be willing and able to give informed consent according to legal requirements.

Exclusion Criteria:

1. Previous or current use of entacapone.

2. History, signs, or symptoms suggesting the diagnosis of secondary or atypical parkinsonism.

3. Unstable Parkinson's disease patients.

4. Patients who experience severe dyskinesia.

5. The following levodopa/carbidopa doses and strengths are not permitted:

   • Patients taking ½ tablet of standard formulation levodopa/carbidopa 100/25
   • Patients taking standard formulation levodopa/carbidopa 100/10 or 250/25
   • Patients taking fewer than 3 or more than 6 daily intakes of standard formulation levodopa/carbidopa 100/25 (fewer than 300mg or more than 600mg of levodopa)

6. Patients with hallucinations or psychiatric diseases related to levodopa or dopamine agonists intake. Patients with major depression.

7. Female patients who are pregnant, trying to become pregnant or nursing (lactating) an infant.

8. Concomitant treatment with MAO-inhibitors (except selegiline up to 10mg/day), rotigotine or neuroleptics, within 60 days prior to the screening visit.

9. Patients with a previous history of Neuroleptic Malignant Syndrome (NMS) and/or non-traumatic rhabdomyolysis.

10. Participated in another trial of an investigational drug/device within the last 30 days prior to study entry.

11. Patients who have a history of poor compliance or are in the Investigator's judgment unlikely to comply with medical regimens or study requirements.