Twelve‐month safety of entacapone in patients with Parkinson’s disease

Abstract

The safety of entacapone combined with levodopa and a dopadecarboxylase (DDC) inhibitor was tested in a 12-month double-blind study of 326 patients with idiopathic Parkinson's disease (PD). The study population represented 'typical' PD outpatients, including patients with varying disease severity and with various concomitant medications. Two-thirds of the patients were randomized to receive 200 mg of entacapone with each of 2--10 daily levodopa doses, and one-third to receive placebo. All entacapone patients were included in the safety evaluation of adverse events (AEs), vital signs, ECG, and laboratory parameters. Entacapone was well tolerated with a discontinuation rate due to AEs of 14% compared with 11% with placebo (NS). As expected, due to dopaminergic enhancement, dyskinesia was more frequent as an AE with entacapone than with placebo. Dryness of mouth, urine discoloration and diarrhoea were more frequent non-dopaminergic AEs with entacapone than with placebo. Entacapone had no adverse effects on hepatic enzyme activity, ECG or haemodynamic parameters, and there was no evidence of any toxicity. As an indication of levodopa enhancement with entacapone, patients taking 5--10 doses of levodopa, most likely representing predominantly fluctuating patients, showed a significant decrease in their mean daily levodopa dose of 94 mg in the entacapone group compared with a decrease of 39 mg in the placebo group (P < 0.01). The interval between the first two morning doses of levodopa increased by 17% with entacapone, whereas with placebo no extension was observed (P < 0.05). Despite levodopa dose reduction, efficacy of entacapone was maintained. As further evidence of efficacy, Parkinsonian symptoms markedly worsened in all patients after withdrawal of entacapone. We conclude that entacapone is safe in optimizing levodopa in long-term treatment of idiopathic Parkinson's disease. Monitoring of liver or other safety parameters during entacapone treatment is not required.

Treatment of End-of-Dose Wearing-Off in Parkinson’s Disease: Stalevo^® (Levodopa/Carbidopa/Entacapone) and Levodopa/DDCI Given in Combination with Comtess^®/Comtan^® (Entacapone) Provide Equivalent Improvements in Symptom Control Superior to That of Traditional Levodopa/DDCI Treatment

“…These studies have shown that completing levodopa therapy with adjunct entacapone consistently increases daily ‘on’ time (and correspondingly decreases ‘off’ time), and results in significantly increased motor function while ‘on’ [13,14,15,16,17]. This current investigation is the first to compare the efficacy of switching to Stalevo versus initiation of separate entacapone with traditional levodopa/DDCI in those patients experiencing end-of-dose wearing-off.…”

“…The efficacy, safety and tolerability of entacapone (in combination with traditional levodopa/DDCI) has been proven in several phase III clinical trials [13,14,15,16,17,18]. These trials have shown that entacapone extends the ‘on’ time up to 1.7 h a day, reduces ‘off’ time (by 1.1–1.6 h a day) and significantly improves motor function and activities of daily living [13,14,15,16,17]. …”

Is There a Difference between Levodopa/ Dopa-Decarboxylase Inhibitor and Entacapone and Levodopa/Dopa-Decarboxylase Inhibitor Dose Fractionation Strategies in Parkinson’s Disease Patients Experiencing Symptom Re-Emergence due to Wearing-Off?

“…These may be managed by reducing the dose of levodopa [4, 6, 11]. The larger number of dopaminergic AEs seen with levodopa/DDCI and entacapone is probably due to the increased levels of plasma levodopa.…”

Patient Diaries As a Clinical Endpoint in Parkinson's Disease Clinical Trials

“…One study had a randomized double blind cross-over design [43], the remaining seven studies had a randomized, double-blind parallel-group design [44][45][46][47][48][49][50]. One was a phase II study [43], the remaining seven were phase III studies.…”