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

Official Title: “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

Intervention(s) in this Clinical Trial

• Drug: Levodopa/carbidopa/entacapone
  • Patients were instructed to take the study medication at the same hours and the same levodopa dose they were taking prior to enrollment in this study. Levodopa/carbidopa/entacapone was available in 2 oral dosage forms: 100/25/200 or 150/37.5/200 mg encapsulated tablets.
• Drug: Levodopa/carbidopa
  • Patients were instructed to take the study medication at the same hours and the same levodopa dose they were taking prior to enrollment in this study. Levodopa/carbidopa was available in 2 oral dosage forms: One or one and one-half 100/25 mg encapsulated tablets.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Levodopa/carbidopa/entacapone
• Active Comparator: Levodopa/carbidopa

Primary Measures

• Change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living [ADL]) Score From Baseline to Month 3
  • Time Frame: Baseline to end of study (Month 3)
    Safety Issue?: No

Secondary Measures

• Change in the UPDRS Part I (Mentation, Behavior, and Mood) Score From Baseline to Month 3
  • Time Frame: Baseline to end of study (Month 3)
    Safety Issue?: No
• Change in the UPDRS Part III (Motor Function) Score From Baseline to Month 3
  • Time Frame: Baseline to end of study (Month 3)
    Safety Issue?: No
• Change in the UPDRS Part IV (Complications of Therapy) Score From Baseline to Month 3
  • Time Frame: Baseline to end of study (Month 3)
    Safety Issue?: No
• Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to Month 3
  • Time Frame: Baseline to end of study (Month 3)
    Safety Issue?: No
• Patient and Investigator Global Evaluation of the Patient
  • Time Frame: Baseline to end of study (Month 3)
    Safety Issue?: No
• Change on the QUICK Questionnaire (QQ) Score From Baseline to Month 3
  • Time Frame: Baseline to end of study (Month 3)
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Novartis Industry

Overall Clinical Trial Officials and Contacts

Eduard Tolosa-Sarró, Dr. Principal Investigator Hospital Clínic i Provincial de Barcelona  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00391898

Study ID Number: CELC200AES03

ClinicalTrials.gov Identifier: NCT00391898

Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios. Ministerio de Sanidad y Consumo