Trial Outcomes & Findings for Effects of Carbidopa/Levodopa/Entacapone on Motor Function and Quality of Life in Patients With Parkinson's Disease (NCT NCT00219284)
NCT ID: NCT00219284
Last Updated: 2017-03-30
Results Overview
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.
COMPLETED
PHASE4
359 participants
Baseline to Week 4
2017-03-30
Participant Flow
Participant milestones
| Measure |
Immediate 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 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.
|
Delayed 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.
|
|---|---|---|
|
Treatment Phase - 16 Weeks
STARTED
|
180
|
179
|
|
Treatment Phase - 16 Weeks
COMPLETED
|
136
|
128
|
|
Treatment Phase - 16 Weeks
NOT COMPLETED
|
44
|
51
|
|
Extension Phase - 8 Weeks
STARTED
|
114
|
106
|
|
Extension Phase - 8 Weeks
COMPLETED
|
112
|
99
|
|
Extension Phase - 8 Weeks
NOT COMPLETED
|
2
|
7
|
Reasons for withdrawal
| Measure |
Immediate 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 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.
|
Delayed 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.
|
|---|---|---|
|
Treatment Phase - 16 Weeks
Adverse Event
|
26
|
24
|
|
Treatment Phase - 16 Weeks
Abnormal laboratory value(s)
|
0
|
1
|
|
Treatment Phase - 16 Weeks
Lack of Efficacy
|
3
|
10
|
|
Treatment Phase - 16 Weeks
Protocol Violation
|
9
|
5
|
|
Treatment Phase - 16 Weeks
Withdrawal by Subject
|
5
|
9
|
|
Treatment Phase - 16 Weeks
Lost to Follow-up
|
1
|
2
|
|
Extension Phase - 8 Weeks
Adverse Event
|
2
|
3
|
|
Extension Phase - 8 Weeks
Withdrawal by Subject
|
0
|
2
|
|
Extension Phase - 8 Weeks
Lost to Follow-up
|
0
|
2
|
Baseline Characteristics
Effects of Carbidopa/Levodopa/Entacapone on Motor Function and Quality of Life in Patients With Parkinson's Disease
Baseline characteristics by cohort
| Measure |
Immediate Switch
n=180 Participants
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.
|
Delayed Switch
n=179 Participants
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
n=359 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
68.7 years
STANDARD_DEVIATION 9.18 • n=93 Participants
|
68.3 years
STANDARD_DEVIATION 10.38 • n=4 Participants
|
68.5 years
STANDARD_DEVIATION 9.78 • n=27 Participants
|
|
Sex: Female, Male
Female
|
74 Participants
n=93 Participants
|
71 Participants
n=4 Participants
|
145 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
106 Participants
n=93 Participants
|
108 Participants
n=4 Participants
|
214 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 4Population: 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.
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.
Outcome measures
| Measure |
Immediate Switch
n=161 Participants
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.
|
Delayed Switch
n=167 Participants
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.
|
|---|---|---|
|
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to Week 4
|
-3.7 Units on a scale
Standard Error 0.66 • Interval -5.02 to -2.41
|
-1.8 Units on a scale
Standard Error 0.58 • Interval -2.95 to -0.68
|
SECONDARY outcome
Timeframe: Baseline to Week 4Population: 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.
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.
Outcome measures
| Measure |
Immediate Switch
n=163 Participants
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.
|
Delayed Switch
n=159 Participants
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.
|
|---|---|---|
|
Change in Parkinson's Disease Quality of Life Score From Baseline to Week 4
|
-0.4 Units on a scale
Standard Error 0.88 • Interval -4.51 to -0.53
|
1.1 Units on a scale
Standard Error 0.77 • Interval -2.84 to 0.66
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: 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.
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.
Outcome measures
| Measure |
Immediate Switch
n=150 Participants
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.
|
Delayed Switch
n=155 Participants
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.
|
|---|---|---|
|
Change in Parkinson's Disease Quality of Life Score From Baseline to Week 8
|
-2.5 Units on a scale
Standard Error 1.01
|
-1.1 Units on a scale
Standard Error 0.89
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: 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.
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.
Outcome measures
| Measure |
Immediate Switch
n=146 Participants
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.
|
Delayed Switch
n=152 Participants
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.
|
|---|---|---|
|
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to Week 8
|
-3.6 Units on a scale
Standard Error 0.71
|
-3.7 Units on a scale
Standard Error 0.62
|
SECONDARY outcome
Timeframe: Baseline to Week 4Population: 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.
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.
Outcome measures
| Measure |
Immediate Switch
n=163 Participants
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.
|
Delayed Switch
n=169 Participants
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.
|
|---|---|---|
|
Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to Week 4
|
-1.7 Units on a scale
Standard Error 1.34
|
0.8 Units on a scale
Standard Error 1.17
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: 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.
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.
Outcome measures
| Measure |
Immediate Switch
n=150 Participants
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.
|
Delayed Switch
n=155 Participants
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.
|
|---|---|---|
|
Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to Week 8
|
-5.8 Units on a scale
Standard Error 1.48
|
-1.9 Units on a scale
Standard Error 1.31
|
SECONDARY outcome
Timeframe: Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)Population: 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.
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.
Outcome measures
| Measure |
Immediate Switch
n=176 Participants
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.
|
Delayed Switch
n=171 Participants
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.
|
|---|---|---|
|
Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III Score From Baseline to End of Treatment
|
-3.6 Units on a scale
Standard Error 0.69
|
-3.3 Units on a scale
Standard Error 0.64
|
SECONDARY outcome
Timeframe: Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)Population: 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.
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.
Outcome measures
| Measure |
Immediate Switch
n=176 Participants
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.
|
Delayed Switch
n=172 Participants
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.
|
|---|---|---|
|
Change in Parkinson's Disease Quality of Life Score From Baseline to End of Treatment
|
-1.3 Units on a scale
Standard Error 0.97
|
0.2 Units on a scale
Standard Error 0.89
|
SECONDARY outcome
Timeframe: Baseline to end of treatment (Week 16 in the Immediate Switch group, Week 20 in the Delayed Switch group)Population: 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.
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.
Outcome measures
| Measure |
Immediate Switch
n=176 Participants
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.
|
Delayed Switch
n=172 Participants
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.
|
|---|---|---|
|
Change in the 39-item Parkinson's Disease Questionnaire (PDQ-39) Total Score From Baseline to End of Treatment
|
-2.8 Units on a scale
Standard Error 1.60
|
0.4 Units on a scale
Standard Error 1.47
|
Adverse Events
Immediate Switch
Delayed Switch
Serious adverse events
| Measure |
Immediate Switch
n=180 participants at risk
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.
|
Delayed Switch
n=179 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.56%
1/180
|
0.00%
0/179
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/180
|
0.56%
1/179
|
|
Cardiac disorders
Bradycardia
|
0.56%
1/180
|
0.00%
0/179
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/180
|
1.1%
2/179
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/180
|
0.56%
1/179
|
|
Cardiac disorders
Sinus bradycardia
|
0.56%
1/180
|
0.00%
0/179
|
|
Eye disorders
Vision blurred
|
0.56%
1/180
|
0.00%
0/179
|
|
Gastrointestinal disorders
Diarrhoea
|
0.56%
1/180
|
0.56%
1/179
|
|
Gastrointestinal disorders
Duodenal ulcer perforation
|
0.56%
1/180
|
0.00%
0/179
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/180
|
0.56%
1/179
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/180
|
0.56%
1/179
|
|
Infections and infestations
Abscess
|
0.00%
0/180
|
0.56%
1/179
|
|
Infections and infestations
Bronchitis
|
0.00%
0/180
|
0.56%
1/179
|
|
Infections and infestations
Viral infection
|
0.00%
0/180
|
0.56%
1/179
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/180
|
0.56%
1/179
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.00%
0/180
|
0.56%
1/179
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/180
|
0.56%
1/179
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/180
|
0.56%
1/179
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/180
|
0.56%
1/179
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/180
|
0.56%
1/179
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/180
|
0.56%
1/179
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
0.00%
0/180
|
0.56%
1/179
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.00%
0/180
|
0.56%
1/179
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
0.56%
1/180
|
0.00%
0/179
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.00%
0/180
|
0.56%
1/179
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma stage unspecified
|
0.00%
0/180
|
0.56%
1/179
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm
|
0.00%
0/180
|
0.56%
1/179
|
|
Nervous system disorders
Cerebrovascular accident
|
0.56%
1/180
|
0.00%
0/179
|
|
Nervous system disorders
Dizziness
|
0.56%
1/180
|
0.00%
0/179
|
|
Nervous system disorders
Global amnesia
|
0.00%
0/180
|
0.56%
1/179
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/180
|
0.56%
1/179
|
|
Nervous system disorders
Presyncope
|
0.56%
1/180
|
0.00%
0/179
|
|
Nervous system disorders
Syncope
|
0.00%
0/180
|
0.56%
1/179
|
|
Psychiatric disorders
Major depression
|
0.00%
0/180
|
0.56%
1/179
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/180
|
0.56%
1/179
|
|
Reproductive system and breast disorders
Breast pain
|
0.00%
0/180
|
0.56%
1/179
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.56%
1/180
|
0.00%
0/179
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/180
|
1.1%
2/179
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.56%
1/180
|
0.00%
0/179
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
0.00%
0/180
|
0.56%
1/179
|
|
Vascular disorders
Hypotension
|
0.56%
1/180
|
0.00%
0/179
|
Other adverse events
| Measure |
Immediate Switch
n=180 participants at risk
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.
|
Delayed Switch
n=179 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
5.6%
10/180
|
3.4%
6/179
|
|
Gastrointestinal disorders
Diarrhoea
|
16.1%
29/180
|
11.7%
21/179
|
|
Gastrointestinal disorders
Nausea
|
17.2%
31/180
|
7.3%
13/179
|
|
General disorders
Fatigue
|
6.7%
12/180
|
3.4%
6/179
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.0%
9/180
|
1.7%
3/179
|
|
Nervous system disorders
Dizziness
|
8.9%
16/180
|
7.3%
13/179
|
|
Nervous system disorders
Dyskinesia
|
3.9%
7/180
|
6.7%
12/179
|
|
Nervous system disorders
Tremor
|
5.0%
9/180
|
3.4%
6/179
|
|
Psychiatric disorders
Depression
|
5.0%
9/180
|
3.9%
7/179
|
|
Renal and urinary disorders
Chromaturia
|
6.7%
12/180
|
5.6%
10/179
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER