Pooled analysis of phase III with entacapone in Parkinson's disease

Kuoppamäki, Mikko; Vahteristo, Mikko; Ellmén, Juha; Kieburtz, Karl

doi:10.1111/ane.12278

Cited by 11 publications

(10 citation statements)

References 24 publications

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“…Entacapone significantly improved daily OFF- and ON-times as well as UPDRS II and III scores irrespective of the DDCI (carbidopa or benserazide) combined with levodopa. These results are well in line with separate reports and the overall pooled analysis of entacapone phase III studies (PSG 1997 ; Rinne et al 1998 ; Poewe et al 2002 ; Brooks and Sagar 2003 ; Kuoppamäki et al 2014 ). An important finding was also that the treatment effects of entacapone (vs placebo) did not differ between patients on LC or LB.…”

Section: Discussionsupporting

confidence: 87%

Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson’s disease patients with wearing-off

2015

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Entacapone is frequently used together with levodopa/carbidopa (LC) and levodopa/benserazide (LB) in the treatment of Parkinson’s disease (PD) patients with wearing-off symptoms. It is generally assumed that the effects of entacapone are independent of the type of decarboxylase inhibitor used, but there is very little published data available on the efficacy of entacapone administered with LB versus LC. We have performed a pooled analysis of three randomized, double-blind, 6-month, phase III studies to compare the treatment effects of entacapone (compared to placebo) in PD patients receiving LC or LB. A total of 551 PD patients experiencing wearing-off were included in the analysis. 300 patients were on LB and 251 on LC at baseline. At 6 months, entacapone (compared to placebo) improved mean daily OFF-time in patients on LB and LC by 0.76 (p = 0.016) and 0.95 (p = 0.011) hours, respectively. The corresponding improvements in ON-time were 0.97 (p = 0.002) and 0.83 h (p = 0.022), respectively. The treatment effects of entacapone both in LB and LC users were statistically significant (p < 0.05) also in UPDRS II and III scores, except in UPDRS II scores in patients receiving LC (p = 0.20). None of the treatment effects of entacapone were statistically significantly different between patients receiving LB or LC. Reported adverse events were comparable between LB and LC users. We conclude that entacapone provided comparable benefits in PD patients with wearing-off symptoms using either LB or LC.

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Section: Discussionsupporting

confidence: 87%

Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson’s disease patients with wearing-off

2015

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“…22,23 Based on a pooled analysis of 4 phase III entacapone trials, this increase in levodopa exposure by entacapone has translated into improved (placebo vs entacapone) daily “on/off” times at 6 months by an average of 0.8 hours. 24 Although no direct comparisons can be made, the present study with ODM-101 combinations demonstrated that increased carbidopa doses administered with levodopa and entacapone almost doubled the treatment effect on “on/off” times previously shown between entacapone and placebo. 24…”

Section: Discussioncontrasting

confidence: 41%

“…24 Although no direct comparisons can be made, the present study with ODM-101 combinations demonstrated that increased carbidopa doses administered with levodopa and entacapone almost doubled the treatment effect on “on/off” times previously shown between entacapone and placebo. 24…”

Section: Discussioncontrasting

confidence: 41%

Increased dose of carbidopa with levodopa and entacapone improves “off” time in a randomized trial

et al. 2019

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ObjectiveTo investigate whether increased fixed carbidopa doses of 65 or 105 mg (ODM-101/65 and ODM-101/105) in combination with 75, 100, 125, or 150 mg of levodopa and 200 mg of entacapone might improve “off” time in fluctuating Parkinson disease (PD) compared to the standard combination of 4:1 levodopa/carbidopa with the usual 200 mg of entacapone (LCE) during a 4-week treatment period.MethodsThis was a randomized, double-blind, double-dummy, active-controlled, crossover, multicenter, phase II, proof-of-concept study in patients with fluctuating PD.ResultsOne hundred seventeen patients were randomized into the study (mean age 67.0 years; daily “off” time 5.3 hours; mean daily levodopa dose 610 mg). Carryover-adjusted mean changes from baseline “off” times were during ODM-101/65, −1.53 hours (p = 0.02 vs LCE), during ODM-101/105, −1.57 hours (p = 0.01 vs LCE), and during LCE −0.91 hours. Changes in daily “on” time without dyskinesia were 1.54 hours (p = 0.005 vs LCE), 1.38 hours (p = 0.0214 vs LCE), and 0.69 hours, respectively. Changes in “on” time with troublesome dyskinesia were <0.1 hours and not significantly different between treatments. In patients with high-activity COMT genotypes Val/Met or Val/Val, “off” time was reduced more with ODM-101/65 and ODM-101/105 than with LCE (p = 0.015 and p = 0.006). No difference between the treatments was seen in safety and tolerability. The most common treatment-related adverse effects were nausea, dizziness, drug-effect decrease, and dyskinesia, which were in most cases mild or moderate in severity. Treatment-related serious adverse events were diarrhea (ODM-101/105 and LCE), and myocardial ischemia and blood creatine kinase increase (LCE).ConclusionIncreasing the dose of carbidopa in combination with levodopa and entacapone should be considered in the treatment of fluctuating PD to improve daily “off” times. Genotyping patients with PD according to COMT activity may improve individual treatment strategies.ClinicalTrials.gov identifierNCT01766258.Classification of evidenceThis study provides Class II evidence that an increased dose of carbidopa improves motor fluctuations when administered with levodopa and entacapone.

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“… 25 In a pooled analysis of published Phase III studies on 808 PD patients, entacapone showed promising results in UPDRS II ( P <0.01) and III ( P <0.01) scores. 26 A meta-analysis of 14 studies also indicated adjuvant treatment with entacapone improved UPDRS ADL and motor scores. 27 Considering the fact that entacapone can increase levodopa sustainability by extending the drug’s half-life, it was reasonable to find that LCE improved scores of UPDRS II and UPDRS III in our study, which is also consistent with previous findings.…”

Section: Discussionmentioning

confidence: 99%

Levodopa/carbidopa/entacapone versus levodopa/dopa-decarboxyiase inhibitor for the treatment of Parkinson's disease: systematic review, meta-analysis, and economic evaluation

Zhou¹,

Qiu²,

Zhang³

et al. 2018

TCRM

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AimsTo review the evidence for efficacy, safety, and cost-effectiveness of levodopa/carbidopa/entacapone (LCE) compared with levodopa/dopa-decarboxyiase inhibitor (DDCI) for Parkinson’s disease (PD).MethodsPubMed, Embase, the Cochrane Library, and Chinese databases WangFang Data, Chinese Sci-tech Journals Database and China National Knowledge Infrastructure, as well as ClinicalTrials.gov, were searched for randomized controlled trials with “levodopa/carbidopa/entacapone” as keywords. The search period was from inception to August 2017. We conducted meta-analyses to synthesize the evidence quantitatively.ResultsA total of 5,693 records were obtained. We included seven randomized controlled trials and one cost-effectiveness study after the screening process. Compared with levodopa–DDCI, LCE improved patient Unified Parkinson’s Disease Rating Scale (UPDRS) II score (mean difference [MD] −1.17, 95% CI −1.64 to −0.71), UPDRS III score (MD −1.55, 95% CI −2.29 to −0.81), and Schwab and England daily activity rating (MD 2.05, 95% CI 0.85–3.26). There was no statistically significant difference in the risk of serious adverse events (AEs) or discontinuation due to AEs in patients with LCE, and the risk of total AEs was higher in the LCE group (risk ratio [RR] 1.33, 95% CI 1.05–1.70). The incremental cost-effectiveness ratio of LCE was £3,105 per quality-adjusted life-year (QALY) gained in the UK.ConclusionLCE can improve PD patients’ motor symptoms and daily living functioning when compared with levodopa/DDCI.

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Pooled analysis of phase III with entacapone in Parkinson's disease

Cited by 11 publications

References 24 publications

Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson’s disease patients with wearing-off

Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson’s disease patients with wearing-off

Increased dose of carbidopa with levodopa and entacapone improves “off” time in a randomized trial

Levodopa/carbidopa/entacapone versus levodopa/dopa-decarboxyiase inhibitor for the treatment of Parkinson's disease: systematic review, meta-analysis, and economic evaluation

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Pooled analysis of phase III with entacapone in Parkinson's disease

Cited by 11 publications

References 24 publications

Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson’s disease patients with wearing-off

Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson’s disease patients with wearing-off

Increased dose of carbidopa with levodopa and entacapone improves “off” time in a randomized trial

Levodopa/carbidopa/entacapone versus levodopa/dopa-decarboxyiase inhibitor for the treatment of Parkinson&#39;s disease: systematic review, meta-analysis, and economic evaluation

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Levodopa/carbidopa/entacapone versus levodopa/dopa-decarboxyiase inhibitor for the treatment of Parkinson's disease: systematic review, meta-analysis, and economic evaluation