There were no clinically relevant differences in demographics between the entacapone (n=85) and placebo (n=86) study groups. Over the 3 days prior to each study visit, patients recorded whether they were "On," "Off," or "in bed" at half-hour intervals over an 18-hour day. During each visit, response to study medication was evaluated through the change in hours of "On" time (periods relatively free of parkinsonian symptoms) while awake, which was the primary outcome measure for this study, and by secondary outcome measures.1
"On" time
During the stable treatment period, the mean awake "On" time in entacapone treated patients increased by 1.5 hours (from 9.3 hours at baseline), compared to a 0.1-hour increase in placebo-treated patients (from 9.2 hours at baseline) (Fig 2). This represents a 1.4-hour difference between these groups in the change from baseline (P<0.001).1, 3 Entacapone withdrawal resulted in a decrease in awake "On" time from stable treatment period values to near baseline values. This decrease was significant when compared to the small change experienced by placebo-treated patients upon withdrawal (P<0.001).1
Figure 2.
The change in the mean time spent in the "On" condition while awake* in patients participating in the Nordic trial.1, 3
Intent-to-treat (ITT) analysis (mean ± the standard error of the mean [SEM]).
*As measured in an 18-hour day.
† P<0.001, difference between treatment groups.
Adapted with permission from Rinne UK et al. Neurology. 1998;51:1309-1314
© Lippincott Williams & Wilkins
"Off" time
During the stable treatment period, the mean awake "Off" time in entacapone-treated patients decreased by 1.3 hours, or 24% (from 5.5 hours at baseline) (Fig 3). In contrast, the mean awake "Off" time for placebo-treated patients remained constant (5.3 hours). The difference in the change of awake "Off" time was 1.3 and was significant between the 2 study groups (P<0.001).1, 3 Entacapone withdrawal resulted in an increase in the duration of "Off" time from stable treatment period values, which was significant when compared to the small change experienced by placebo-treated patients upon withdrawal (P<0.001).1
Figure 3.
The change in the mean time spent in the "Off" condition while awake* in patients participating in the Nordic trial.1, 3
ITT analysis (mean ± SEM).
*As measured in an 18-hour day.
† P<0.001, difference between treatment groups.
Additional data on file, Orion Corporation, Finland.
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UPDRS scores
Patient total and subscale UPDRS scores were assessed in both study groups at baseline and at week 24. Evaluations were performed in the morning, while patients were "On," 1.5 to 1.8 hours after entacapone administration. Entacapone-treated patients experienced significant improvements in mean total UPDRS scores (P<0.01), as well as in part II (activities of daily living [ADL]) [P<0.05] and part III (motor examination) [P<0.05] subscale scores from baseline to week 24, in comparison with placebo-treated patients (Table 3). The improvement in the ADL subscale scores has particular clinical significance, as these scores reflect a patient's ability to complete the essential tasks of day-to-day life (eg, speaking, dressing, handwriting, cutting food and handling utensils, walking).1,3 By 2 weeks postwithdrawal, entacapone-treated patients experienced a significant worsening in mean total UPDRS (P<0.001), ADL (P<0.001), and motor subscale (P<0.01) scores from week 24 values, in comparison to placebo-treated patients, indicating a deterioration of motor functional ability.1
ITT analysis.
UPDRS = Unified Parkinson's Disease Rating Scale; ADL = activities of daily living.
*Measured while patients were "On."
† P value, compared to placebo-treated group.
aStable treatment period values are the average of values measured at weeks 8, 16, and 24, by protocol-defined outcome measure.
Levodopa dose
The levodopa dose was recorded for each patient at each study visit. During the stable treatment period, the mean daily levodopa dose was reduced in entacapone-treated patients by about 12% (from 701 mg at baseline to 614 mg) to manage dopaminergic side effects, and increased in placebo-treated patients by about 2% (from 705 mg at baseline to 719 mg) (Fig 4). The difference in the change of daily levodopa dose between the 2 study groups was significant (P<0.001).1, 3 By 2 weeks postwithdrawal, entacapone-treated patients required a mean increase in daily levodopa dose of approximately 50 mg, compared to the mean dose in the stable treatment period, to control motor symptoms. 1, 3
Figure 4.The mean daily levodopa dose for patients participating in the Nordic trial.1, 3
ITT analysis (mean ± SEM).
*P<0.001, difference between treatment groups.
Additional data on file, Orion Corporation, Finland.
