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

Phase 3

Completed

Conditions: Parkinson's Disease

Interventions: Drug: Carbidopa/levodopa/entacapone
Drug: Immediate release carbidopa/levodopa

Registration Number: NCT00099268

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 747

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carbidopa/levodopa/entacapone	Carbidopa/levodopa/entacapone	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.
Immediate release carbidopa/levodopa	Immediate release carbidopa/levodopa	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.

Primary Outcome Measures

Name	Time	Method
Time to First Occurrence of Dyskinesia	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	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Total Score (Parts II and III)	Baseline, Week 6 and Week 130	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.
Occurrence of Wearing-off	Baseline to Week 134	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.
Time to First Occurrence of Wearing-off	Baseline to end of study (134-208 weeks of treatment)	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.
Occurrence of Dyskinesia	Baseline to Week 208	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?"
Change From Baseline in Health-related Quality of Life Assessed Using the 39-item Parkinson's Disease Questionnaire (PDQ-39)	Baseline to Week 156	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.

Trial Locations

Locations (32): Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Keck School of Medicine, Division of Movement Disorders
🇺🇸
Los Angeles, California, United States
Reed Neurological Research Center
🇺🇸
Los Angeles, California, United States
Clinical Neuroscience Center
🇺🇸
Southfield, Michigan, United States
Wesley Woods Health Center
🇺🇸
Atlanta, Georgia, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸
Dallas, Texas, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Ochsner Clinic Foundation
🇺🇸
New Orleans, Louisiana, United States
Novartis Investigative Site
🇬🇧
Newcastle Upon Tyne, United Kingdom
The Parkinson's Institute
🇺🇸
Sunnyvale, California, United States
Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
Duke University Medical Center Movement Disorders Center
🇺🇸
Durham, North Carolina, United States
Parkinson's Disease and Movement Disorder Center of Albany Medical
🇺🇸
Albany, New York, United States
Pennsylvania Neurology Institute
🇺🇸
Philadelphia, Pennsylvania, United States
Parkinson's Disease and Movement Disorders Center of Long Island
🇺🇸
Commack, New York, United States
Semmes-Murphey Clinic
🇺🇸
Memphis, Tennessee, United States
NeuroHealth, Inc.
🇺🇸
Warwick, Rhode Island, United States
Columbia University, Neurological Institute
🇺🇸
New York, New York, United States
Coastal Neurological Medical Group
🇺🇸
La Jolla, California, United States
Molecular NeuroImaging, LLC
🇺🇸
New Haven, Connecticut, United States
Charlotte Neurological Service
🇺🇸
Port Charlotte, Florida, United States
Northwestern University Medical School
🇺🇸
Chicago, Illinois, United States
Landon Center on Aging
🇺🇸
Kansas City, Kansas, United States
Boston University School of Medicine
🇺🇸
Boston, Massachusetts, United States
Medical College of Georgia
🇺🇸
Augusta, Georgia, United States
Wisconsin Institute for Neurologic and Sleep Disorders
🇺🇸
Milwaukee, Wisconsin, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Parkinson's Disease and Movement Disorder Center
🇺🇸
Boca Raton, Florida, United States
Baylor College of Medicine, Parkinson's Disease Center
🇺🇸
Houston, Texas, United States
University of South Florida
🇺🇸
Tampa, Florida, United States
Mayo Clinic
🇺🇸
Scottsdale, Arizona, United States
University of Miami
🇺🇸
Miami, Florida, United States