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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00219284
• Collaborator: (none)
• Enrollment: 359
• Locations: 42
• Arms: 2
• Duration (Months): 42
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease With End of Dose Wearing Off	Drug: Carbidopa/levodopa/entacapone	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 359 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Immediate switch 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.	Drug: Carbidopa/levodopa/entacapone; Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to carbidopa/levodopa/entacapone.
Active Comparator: Delayed switch 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.	Drug: Carbidopa/levodopa/entacapone; Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to carbidopa/levodopa/entacapone.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States	85006
2		Fullerton	California	United States	92835
3		Irvine	California	United States	92618
4		La Jolla	California	United States	92037
5		Los Angeles	California	United States	90033
6		Pasadena	California	United States	91105
7		Reseda	California	United States	91355
8		Stanford	California	United States	94305
9		Ft. Collins	Colorado	United States	80524
10		Washington DC	District of Columbia	United States	20007
11		Boca Raton	Florida	United States	33486
12		Bradenton	Florida	United States	34205
13		Fort Lauderdale	Florida	United States	33308
14		Hollywood	Florida	United States	33021
15		Naples	Florida	United States	34102
16		Palm Beach	Florida	United States	33418
17		Plantation	Florida	United States	33324
18		Pompano Beach	Florida	United States	33060
19		Port Charlotte	Florida	United States	33952
20		Chicago	Illinois	United States	60637
21		Flossmoor	Illinois	United States	60402
22		Lenexa	Kansas	United States	66214
23		Topeka	Kansas	United States	66606
24		Baltimore	Maryland	United States	21201
25		Bingham Farms	Michigan	United States	48025
26		Southfield	Michigan	United States	48034
27		Hattiesburg	Mississippi	United States	39401
28		Columbia	Missouri	United States	65201
29		St. Louis	Missouri	United States	63141
30		Ridgewood	New Jersey	United States	07450
31		Commack	New York	United States	11725
32		Durham	North Carolina	United States	27705
33		Raleigh	North Carolina	United States	27607
34		Bellevue	Ohio	United States	44811
35		Canton	Ohio	United States	44718
36		Tualatin	Oregon	United States	97602
37		East Stroudsburg	Pennsylvania	United States	18301
38		Houston	Texas	United States	77030
39		Spokane	Washington	United States	99204
40		Tacoma	Washington	United States	98405
41		Milwaukee	Wisconsin	United States	53233
42		Caroline		Puerto Rico	00983

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00219284
• Other Study ID Numbers: CELC200AUS11
• First Posted: Sep 22, 2005
• Last Update Posted: Mar 30, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Novartis Pharmaceuticals: Parkinson's disease, tremor
• Additional relevant MeSH terms: Parkinson Disease; Levodopa; Carbidopa; Entacapone; Carbidopa, levodopa drug combination

Study Results

Participant Flow

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Period Title: Treatment Phase - 16 Weeks
STARTED	180	179
COMPLETED	136	128
NOT COMPLETED	44	51
Period Title: Treatment Phase - 16 Weeks
STARTED	114	106
COMPLETED	112	99
NOT COMPLETED	2	7

Baseline Characteristics

Arm/Group Title	Immediate Switch	Delayed Switch	Total
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Total of all reporting groups
Overall Participants	180	179	359
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.7 (9.18)	68.3 (10.38)	68.5 (9.78)
Sex: Female, Male (Count of Participants)
Female	74 41.1%	71 39.7%	145 40.4%
Male	106 58.9%	108 60.3%	214 59.6%

Outcome Measures

1. Primary Outcome

Title	Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to Week 4
Description	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.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable. Only patients with baseline and Week 4 UPDRS part III scores were included in the analysis.

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Measure Participants	161	167
Least Squares Mean (Standard Error) [Units on a scale]	-3.7 (0.66)	-1.8 (0.58)

2. Secondary Outcome

Title	Change in Parkinson's Disease Quality of Life Score From Baseline to Week 4
Description	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.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable. Only patients with baseline and Week 4 PDQUALIF scores were included in the analysis.

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Measure Participants	163	159
Least Squares Mean (Standard Error) [Units on a scale]	-0.4 (0.88)	1.1 (0.77)

3. Secondary Outcome

Title	Change in Parkinson's Disease Quality of Life Score From Baseline to Week 8
Description	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.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable. Only patients with baseline and Week 8 PDQUALIF scores were included in the analysis.

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Measure Participants	150	155
Least Squares Mean (Standard Error) [Units on a scale]	-2.5 (1.01)	-1.1 (0.89)

4. Secondary Outcome

Title	Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to Week 8
Description	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.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable. Only patients with baseline and Week 8 UPDRS part III scores were included in the analysis.

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Measure Participants	146	152
Least Squares Mean (Standard Error) [Units on a scale]	-3.6 (0.71)	-3.7 (0.62)

5. Secondary Outcome

Title	Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to Week 4
Description	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.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable. Only patients with baseline and Week 4 PDQ-39 scores were included in the analysis.

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Measure Participants	163	169
Least Squares Mean (Standard Error) [Units on a scale]	-1.7 (1.34)	0.8 (1.17)

6. Secondary Outcome

Title	Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to Week 8
Description	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.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All randomized patients who received at least one dose of study drug and had at least one post-baseline assessment of the primary efficacy variable. Only patients with baseline and Week 8 PDQ-39 scores were included in the analysis.

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Measure Participants	150	155
Least Squares Mean (Standard Error) [Units on a scale]	-5.8 (1.48)	-1.9 (1.31)

7. Secondary Outcome

Title	Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to End of Treatment
Description	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.
Time Frame	Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)

Outcome Measure Data

Analysis Population Description

ITT population - For each patient, the last post-baseline measurement during the treatment phase was used as the end-of-treatment measurement. Only patients with baseline and end-of-treatment UPDRS part III scores were included in the analysis.

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Measure Participants	176	171
Least Squares Mean (Standard Error) [Units on a scale]	-3.6 (0.69)	-3.3 (0.64)

8. Secondary Outcome

Title	Change in Parkinson's Disease Quality of Life Score From Baseline to End of Treatment
Description	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.
Time Frame	Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)

Outcome Measure Data

Analysis Population Description

ITT population - For each patient, the last post-baseline measurement during the treatment phase was used as the end-of-treatment measurement. Only patients with baseline and end-of-treatment PDQUALIF scores were included in the analysis.

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Measure Participants	176	172
Least Squares Mean (Standard Error) [Units on a scale]	-1.3 (0.97)	0.2 (0.89)

9. Secondary Outcome

Title	Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to End of Treatment
Description	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.
Time Frame	Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)

Outcome Measure Data

Analysis Population Description

ITT population - For each patient, the last post-baseline measurement during the treatment phase was used as the end-of-treatment measurement. Only patients with baseline and end-of-treatment PDQ-39 scores were included in the analysis.

Arm/Group Title	Immediate Switch	Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
Measure Participants	176	172
Least Squares Mean (Standard Error) [Units on a scale]	-2.8 (1.60)	0.4 (1.47)

Adverse Events

Arm/Group Title	Immediate Switch		Delayed Switch
Arm/Group Description	Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.		Carbidopa/levodopa/entacapone was administered in 1 of 3 dose combinations: 12.5/50/200 mg, 25/100/200 mg, or 37.5/150/200 mg. The selected combination dose contained the same doses of carbidopa and levodopa the patient was receiving prior to switching to 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.
All Cause Mortality
	Immediate Switch		Delayed Switch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Immediate Switch		Delayed Switch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/180 (4.4%)		12/179 (6.7%)
Blood and lymphatic system disorders
Anaemia	1/180 (0.6%)		0/179 (0%)
Cardiac disorders
Atrial fibrillation	0/180 (0%)		1/179 (0.6%)
Bradycardia	1/180 (0.6%)		0/179 (0%)
Cardiac failure congestive	0/180 (0%)		2/179 (1.1%)
Myocardial infarction	0/180 (0%)		1/179 (0.6%)
Sinus bradycardia	1/180 (0.6%)		0/179 (0%)
Eye disorders
Vision blurred	1/180 (0.6%)		0/179 (0%)
Gastrointestinal disorders
Diarrhoea	1/180 (0.6%)		1/179 (0.6%)
Duodenal ulcer perforation	1/180 (0.6%)		0/179 (0%)
Pancreatitis acute	0/180 (0%)		1/179 (0.6%)
Vomiting	0/180 (0%)		1/179 (0.6%)
Infections and infestations
Abscess	0/180 (0%)		1/179 (0.6%)
Bronchitis	0/180 (0%)		1/179 (0.6%)
Viral infection	0/180 (0%)		1/179 (0.6%)
Injury, poisoning and procedural complications
Humerus fracture	0/180 (0%)		1/179 (0.6%)
Intentional overdose	0/180 (0%)		1/179 (0.6%)
Joint dislocation	0/180 (0%)		1/179 (0.6%)
Metabolism and nutrition disorders
Anorexia	0/180 (0%)		1/179 (0.6%)
Dehydration	0/180 (0%)		1/179 (0.6%)
Hypokalaemia	0/180 (0%)		1/179 (0.6%)
Musculoskeletal and connective tissue disorders
Back pain	0/180 (0%)		1/179 (0.6%)
Chest wall pain	0/180 (0%)		1/179 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer	0/180 (0%)		1/179 (0.6%)
Papillary thyroid cancer	1/180 (0.6%)		0/179 (0%)
Renal cancer	0/180 (0%)		1/179 (0.6%)
Renal cell carcinoma stage unspecified	0/180 (0%)		1/179 (0.6%)
Renal neoplasm	0/180 (0%)		1/179 (0.6%)
Nervous system disorders
Cerebrovascular accident	1/180 (0.6%)		0/179 (0%)
Dizziness	1/180 (0.6%)		0/179 (0%)
Global amnesia	0/180 (0%)		1/179 (0.6%)
Hypoaesthesia	0/180 (0%)		1/179 (0.6%)
Presyncope	1/180 (0.6%)		0/179 (0%)
Syncope	0/180 (0%)		1/179 (0.6%)
Psychiatric disorders
Major depression	0/180 (0%)		1/179 (0.6%)
Suicidal ideation	0/180 (0%)		1/179 (0.6%)
Reproductive system and breast disorders
Breast pain	0/180 (0%)		1/179 (0.6%)
Ovarian cyst	1/180 (0.6%)		0/179 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/180 (0%)		2/179 (1.1%)
Skin and subcutaneous tissue disorders
Cold sweat	1/180 (0.6%)		0/179 (0%)
Dermatitis allergic	0/180 (0%)		1/179 (0.6%)
Vascular disorders
Hypotension	1/180 (0.6%)		0/179 (0%)
Other (Not Including Serious) Adverse Events
	Immediate Switch		Delayed Switch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	100/180 (55.6%)		66/179 (36.9%)
Gastrointestinal disorders
Constipation	10/180 (5.6%)		6/179 (3.4%)
Diarrhoea	29/180 (16.1%)		21/179 (11.7%)
Nausea	31/180 (17.2%)		13/179 (7.3%)
General disorders
Fatigue	12/180 (6.7%)		6/179 (3.4%)
Musculoskeletal and connective tissue disorders
Pain in extremity	9/180 (5%)		3/179 (1.7%)
Nervous system disorders
Dizziness	16/180 (8.9%)		13/179 (7.3%)
Dyskinesia	7/180 (3.9%)		12/179 (6.7%)
Tremor	9/180 (5%)		6/179 (3.4%)
Psychiatric disorders
Depression	9/180 (5%)		7/179 (3.9%)
Renal and urinary disorders
Chromaturia	12/180 (6.7%)		10/179 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.