Efficacy of levodopa/carbidopa/entacapone versus levodopa/carbidopa in patients with early Parkinson’s disease experiencing mild wearing-off: a randomised, double-blind trial

Abstract

To compare the efficacy and safety of levodopa/carbidopa/entacapone (LCE) with levodopa/carbidopa (LC) on Parkinson's disease (PD) patients with mild, or only minimally disabling motor complications. A prospective 3-month, multicentre, parallel-group, double-blind, and randomised phase IV study was performed. The primary endpoint was to assess the efficacy of LCE compared to LC on ADLs using the UPDRS part II. Secondary endpoints were assessed by the UPDRS (I, III and IV) scores, QUICK and PDQ-39 questionnaires, and patient and investigator clinical global impression (CGI). Ninety-five patients were randomly assigned to treatment with LCE (100/25/200 or 150/37.5/200 mg tablets, n = 46) or LC (100/25 mg tablets, n = 49), at the same levodopa dose that were administered before randomization. Treatment with LCE resulted in significantly greater improvement in UPDRS part II (ADLs) scores compared to treatment with LC (adjusted mean difference between groups of -1.5 points) (p = 0.0288). Amelioration was also observed in UPDRS part III scores (p = 0.010), and CGI (patient and investigator) scores (p = 0.015, and p = 0.028, respectively). LCE and LC were generally well tolerated with 78 % of subjects completing the study. Most AEs (50 % in LCE and 71.4 % in LC) were classified as mild. No serious AEs were related to the treatment. Treatment with LCE results in improved efficacy compared to LC in PD patients with mild, or minimally disabling motor fluctuations, maintaining a good safety and tolerability profile.

International Parkinson and movement disorder society evidence‐based medicine review: Update on treatments for the motor symptoms of Parkinson's disease

“…COMT Inhibitors . A total of 3 high‐quality positive studies, evaluated entacapone, with the conclusions remaining as “efficacious” and “clinically useful.” There were no new safety concerns. There were no new studies evaluating tolcapone, and the conclusion remains unchanged.…”

Rasagiline monotherapy in early Parkinson's disease: A phase 3, randomized study in Japan

“…Because the present study was not powered to detect changes in this measure, a potential reason for this lack of significance is the relatively low PDQ-39 summary index score observed for both treatment groups at baseline, which implies that a greater number of patients would have been required to detect a significant difference. Furthermore, the relative insensitivity to change of this measure in patients with early PD has been previously suggested in entacapone studies [27,28]. Nevertheless, for the activities of daily living and emotional well-being sub-scores, a statistically significant difference in the change from baseline was observed in rasagiline patients compared with placebo.…”

Outcome Measurement in Neurodegenerative Disease: Attributes, Applications & Interpretation

“…To date, use of the measure has been reported in over 370 studies. Such studies encompass a range of randomized controlled trials including, for example, pharmaceutical trials [50,51], surgical trials [52,53], nonpharmaceutical therapy trials [54,55] and clinical practice trials [56,57]. Additionally, the measure has been extensively used in descriptive surveys including, for example, studies relating to mood [58,59], nutrition [60,61], exercise [62,63] and personality style [64,65].…”