Efficacy and Safety of Carbidopa/Levodopa/Entacapone in Patients With Parkinson's Disease Requiring Initiation of Levodopa Therapy

Study Overview
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Brief Summary
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The CELC200A2401 study has been designed in order to evaluate the hypothesis that administering the combination carbidopa/levodopa/entacapone at the time that levodopa therapy is initiated results in a decrease in the risk of the development of motor complications for patients with Parkinson's disease.

Official Title
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A Long Term, Double-blind, Randomized, Parallel-group, Carbidopa/Levodopa Controlled, Multi-center Study to Evaluate the Effect of Carbidopa/Levodopa/Entacapone in Patients With Parkinson's Disease Requiring Initiation of Levodopa Therapy

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Carbidopa/levodopa/entacapone
* Drug: Immediate release carbidopa/levodopa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of idiopathic Parkinson's disease Diagnosis of Parkinson's disease for no more than 5 years Exclusion Criteria: History, signs, or symptoms of atypical or secondary parkinsonism Presence at baseline of drug-related wearing-off symptoms, dyskinesia or other motor complications Levodopa exposure of more than 30 days or anytime within 8 weeks prior to visit 1 Other inclusion/exclusion criteria applied to this study.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carbidopa/levodopa/entacapone<br>Patients received Carbidopa/levodopa/entacapone tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks. | Drug: Carbidopa/levodopa/entacapone<br>* Carbidopa/Levodopa/Entacapone 12.5/50/200 mg and 25/100/200 mg capsules.<br>* Other names: Stalevo;|
| Active Comparator: Immediate release carbidopa/levodopa<br>Patients received Immediate release carbidopa/levodopa tablets. The study was designed as a flexible dose trial (200-1000 mg/day levodopa). The target dose was 400 mg/day levodopa administered orally as 4 equal doses 4 times a day with 3.5-hour dosing intervals for a treatment period of 134 to 208 weeks. | Drug: Immediate release carbidopa/levodopa<br>* Immediate release carbidopa/levodopa 12.5/50 mg and 25/100 mg capsules.<br>* Other names: Sinemet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Occurrence of Dyskinesia | Dyskinesia was assessed by a blinded rater at each visit. Time to dyskinesia was defined as the visit at which the rater first answered yes to the following question: In your opinion, does this patient have dyskinesia? Time to dyskinesia was estimated by Kaplan-Meier product limit estimate that takes into consideration patients who did not experience dyskinesia by censoring them at the end of the study. | Treatment duration for an individual patient varied between a minimum of 134 weeks for those patients recruited last and a maximum of 208 weeks for those patients recruited first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score (Parts II and III) | The UPDRS is a standardized assessment scale used to measure the patient's disease state. It was to be completed by a blinded rater. There are 6 parts to the UPDRS. Part II (items 5-17; total score 0-52 units on the scale) measures the patient's activities of daily living and part III (items 18-31; total score 0-56 units on the scale) measures the motor function of the patient. The total score ranges from 0 to 108 units on the scale. A higher score indicates greater disability. A negative change score indicates improvement. | Baseline, Week 6 and Week 130 | 
| Occurrence of Wearing-off | Wearing-off is defined as a perception of loss of mobility or dexterity, usually taking place gradually over minutes (up to an hour) and usually bearing a close temporal relationship to the timing of anti-parkinsonian medications; it does not include early-morning akinesia. To ascertain its occurrence, a blinded rater questioned the patient as to whether he/she had noticed that the benefits of the study drug were wearing-off. | Baseline to Week 134 | 
| Time to First Occurrence of Wearing-off | Wearing off is defined as a perception of loss of mobility or dexterity, usually taking place gradually over minutes (up to an hour) and usually bearing a close temporal relationship to the timing of anti-parkinsonian medications; it does not include early-morning akinesia. To ascertain its occurrence, a blinded rater questioned the patient whether he/she had noticed that the benefits of the study drug wear-off. A motor complications and patient questionnaire card were provided to assist the blinded rater in determining whether a patient had experienced wearing-off. | Baseline to end of study (134-208 weeks of treatment) | 
| Occurrence of Dyskinesia | Dyskinesia was assessed by a blinded rater at each visit. Time to dyskinesia was defined as the visit at which the rater first answered yes to the following question: In your opinion, does this patient have dyskinesia? | Baseline to Week 208 | 
| Change From Baseline in Health-related Quality of Life Assessed Using the 39-item Parkinson's Disease Questionnaire (PDQ-39) | The PDQ-39 instrument is used to assess quality of life in individuals with Parkinson's disease. The questionnaire provides scores on eight scales: Mobility, activities of daily living, emotions, stigma, social support, cognition, communication, and bodily discomfort. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The total score can range from 39 to 190. A lower score indicates better quality of life. A negative change score indicates an improvement. | Baseline to Week 156 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, levodopa therapy, dyskinesia