Effects of Carbidopa/Levodopa/Entacapone on Motor Function and Quality of Life in Patients With Parkinson's Disease

Phase 4

Completed

Conditions: Parkinson's Disease With End of Dose Wearing Off

Interventions: Drug: Carbidopa/levodopa/entacapone

Registration Number: NCT00219284

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: To assess motor function and quality of life (QoL) in Parkinson's disease (PD) subjects with end-of-dose wearing off, comparing immediate and delayed switch to carbidopa/levodopa and entacapone.

Detailed Description: This was a prospective, multi-center, randomized, open-label study with blinded raters to evaluate the effects of immediate versus delayed switch to carbidopa/levodopa/entacapone on motor function and quality of life in patients with Parkinson's disease with end-of-dose wearing off.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 359

Inclusion Criteria

Males or females 30-80 years of age (inclusive). Patients aged 81-85 years were eligible to participate if the principal investigator considered the patient to be in otherwise good health.
Clinical diagnosis of Parkinson's disease exhibiting two of three symptoms (rigidity, resting tremor, bradykinesia).
All patients were required to have end-of dose wearing off (EODWO, re-emergence of PD symptoms at the end of at least two daily doses of levodopa during waking hours).
Taking regular doses of immediate release carbidopa/levodopa

Exclusion Criteria

Unstable Parkinson's Disease requiring booster doses or treatment with as needed dose regimens of levodopa
Female subjects who are pregnant, trying to become pregnant or nursing an infant

Other protocol-defined inclusion/exclusion criteria applied to this study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Delayed switch	Carbidopa/levodopa/entacapone	Patients were switched 4 weeks after randomization from combined carbidopa/levodopa to combined carbidopa/levodopa/entacapone. Patients received the same doses of carbidopa (12.5, 25.0, or 37.5 mg) and levodopa (50, 100, or 150 mg) they were receiving prior to the switch, combined with 200 mg of entacapone. The frequency of doses per day prior to the switch remained the same after the switch.
Immediate switch	Carbidopa/levodopa/entacapone	Patients were switched the day after randomization from combined carbidopa/levodopa to combined carbidopa/levodopa/entacapone. Patients received the same doses of carbidopa (12.5, 25.0, or 37.5 mg) and levodopa (50, 100, or 150 mg) they were receiving prior to the switch, combined with 200 mg of entacapone. The frequency of doses per day prior to the switch remained the same after the switch.

Primary Outcome Measures

Name	Time	Method
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to Week 4	Baseline to Week 4	Motor function was assessed with the UPDRS part III. There are 14 items in the instrument, each measured on a 5 point scale (0-4): Speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. The sum of scores can range from 0 to 56; a higher score indicates greater disability. A negative change score indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Change in Parkinson's Disease Quality of Life Score From Baseline to Week 8	Baseline to Week 8	Quality of life was assessed with the Parkinson's Disease Quality of Life Instrument (PDQUALIF), a 33-item self-reported questionnaire which includes seven domains: Social/role function, self-imaging/sexuality, sleep, outlook, physical function, independence, and urinary function. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 132. A lower score indicates better quality of life. A negative change score indicates improvement.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to End of Treatment	Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)	Motor function was assessed with the UPDRS part III. There are 14 items in the instrument, each measured on a 5 point scale (0-4): Speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. The sum of scores can range from 0 to 56; a higher score indicates greater disability. A negative change score indicates improvement.
Change in Parkinson's Disease Quality of Life Score From Baseline to End of Treatment	Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)	Quality of life was assessed with the Parkinson's Disease Quality of Life Instrument (PDQUALIF), a 33-item self-reported questionnaire which includes seven domains: Social/role function, self-imaging/sexuality, sleep, outlook, physical function, independence, and urinary function. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 132. A lower score indicates better quality of life. A negative change score indicates improvement.
Change in Parkinson's Disease Quality of Life Score From Baseline to Week 4	Baseline to Week 4	Quality of life was assessed with the Parkinson's Disease Quality of Life Instrument (PDQUALIF), a 33-item self-reported questionnaire which includes seven domains: Social/role function, self-imaging/sexuality, sleep, outlook, physical function, independence, and urinary function. Questions are scored on a 5-point Likert scale ranging from 1 (never) to 3 (sometimes) to 5 (always). The 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 132. A lower score indicates better quality of life. A negative change score indicates improvement.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to Week 8	Baseline to Week 8	Motor function was assessed with the UPDRS part III. There are 14 items in the instrument, each measured on a 5-point scale (0-4): Speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. The sum of scores can range from 0 to 56; a higher score indicates greater disability. A negative change score indicates improvement.
Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to Week 4	Baseline to Week 4	The PDQ-39 is another instrument 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 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 156. A lower score indicates better quality of life. A negative change score indicates an improvement.
Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to Week 8	Baseline to Week 8	The PDQ-39 is another instrument 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 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 156. A lower score indicates better quality of life. A negative change score indicates an improvement.
Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to End of Treatment	Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)	The PDQ-39 is another instrument 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 1 to 5 range was recoded to 0 to 4 for the analysis. The total score can range from 0 to 156. A lower score indicates better quality of life. A negative change score indicates an improvement.