Efficacy Of Opicapone Research Articles

Efficacy of opicapone in Parkinson’s disease patients with ‘early’ motor fluctuations: Patient and clinical global impression of change from the BIPARK-I double-blind experience

Efficacy of opicapone in Parkinson’s disease patients with ‘early’ motor fluctuations: Patient and clinical global impression of change from the BIPARK-I double-blind experience

Influence of baseline off-time in the efficacy response of Parkinson's disease patients with motor fluctuations: Post-hoc analysis from combined BIPARK-I and II

To evaluate the impact of baseline OFF-time on the efficacy of opicapone (OPC) in levodopa-treated Parkinson's Disease (PD) patients with motor fluctuations. OPC, a once-daily COMT inhibitor, proved effective in the treatment of motor fluctuations in PD patients in two large, pivotal, multinational trials (BIPARK-I and II) [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. Patient-level data from matching treatment arms in BIPARK-I and II were combined in placebo (PLC) and OPC-50 mg groups. The studies had similar designs (primary efficacy endpoint: change from baseline in patient diaries-based absolute OFF-time) and eligibility criteria [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. An exploratory post-hoc analysis was performed to evaluate the influence of baseline OFF-time in efficacy outcomes (i.e., change from baseline in OFF-/ON-time). Linear regression was applied and the slope was statistically tested for deviation from zero. 1027 patients were randomized to BIPARK-I and II; 522 patients took a dose of study medication; Full Analysis Set comprised 517 [PLC (n = 255); OPC-50 mg (n = 262)]. As expected, both treatments arms presented the same increased dependent tendency for OFF-/ON-time at endpoint, i.e., the longer OFF-time at baseline the greater magnitude of response at endpoint (ending in a linear regression slope statistically significant). When OFF-time at endpoint was ‘normalized’ as % of change in relation to baseline, the linear regression slope was found non-significant for both treatment arms, though the increased dependent tendency was still found. Baseline OFF-time appears to impact the magnitude of both OFF- and ON-time responses in a clinical study setting.

Efficacy of opicapone in Parkinson’s disease patients according to baseline rasagiline use: A post-hoc analysis from combined BIPARK-I and II

To evaluate opicapone’s (OPC) efficacy in levodopa-treated Parkinson’s Disease (PD) patients with or without concurrent rasagiline use (CRU). OPC, a once-daily COMT inhibitor, proved effective in the treatment of motor fluctuations in PD patients in two large, pivotal, multinational trials (BIPARK-I and II) [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. Patient-level data from matching treatment arms in BIPARK-I and II were combined in placebo (PLC) and OPC-50 mg groups. Studies had similar designs (primary efficacy endpoint: change from baseline in patient diaries-based absolute OFF-time) and eligibility criteria [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. This exploratory post-hoc analysis was performed to evaluate OPC-50 mg and PLC efficacies in levodopa-treated PD patients with or without baseline CRU (the most commonly used MAO-B inhibitor). In total, 535 patients were randomized; Full Analysis Set comprised 517 [PLC (n = 255); OPC-50 mg (n = 262)]. 12 (PLC) to 15% (OPC-50 mg) of patients were using rasagiline at baseline. Mean placebo-adjusted OFF-time reductions were −81.1 min (p = 0.0469) and −54.2 min (p = 0.0002) for OPC-50 mg patients with and without CRU. There was ~35% more OFF-time reduction in PLC patients without CRU than in those with, but ~9% less OFF-time reduction in OPC-50 mg patients without CRU than in those with. A higher-than-PLC proportion of OPC-50 mg-receiving patients with CRU achieved OFF- (40.0% vs. 66.7%; p = 0.0283) and ON-time (40.0% vs. 64.1%; p = 0.0491) responders’ endpoint. Consistently, a higher-than-PLC proportion of OPC-50 mg-receiving patients without CRU achieved OFF- (50.2% vs. 67.7%; p = 0.0002) and ON-time (46.2% vs. 63.2%; p = 0.0003) responders’ endpoint. Opicapone was effective regardless of concurrent rasagiline use.

Efficacy of opicapone in Parkinson’s disease patients according to baseline pramipexole use: A post-hoc analysis from combined BIPARK-I and II

To evaluate opicapone’s (OPC) efficacy in levodopa-treated Parkinson’s Disease (PD) patients with or without concurrent pramipexole use (CPU). OPC, a once-daily COMT inhibitor, proved effective in the treatment of motor fluctuations in PD patients in two large, pivotal, multinational trials (BIPARK-I and II) [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. Patient-level data from matching treatment arms in BIPARK-I and II were combined in placebo (PLC) and OPC-50 mg groups. Studies had similar designs (primary efficacy endpoint: change from baseline in patient diaries-based absolute OFF-time) and eligibility criteria [[1]Ferreira et al.Lancet Neurol. 2016; 15: 154-165Google Scholar,[2]Lees et al.JAMA Neurol. 2017; 74: 197-206Google Scholar]. This exploratory post-hoc analysis was performed to evaluate OPC-50 mg and PLC efficacies in levodopa-treated PD patients with or without baseline CPU (the most commonly used dopamine agonist). In total, 535 patients were randomized; Full Analysis Set comprised 517 [PLC (n = 255); OPC-50 mg (n = 262)]. About 37% of patients in each arm were using pramipexole at baseline. Mean placebo-adjusted OFF-time reductions were −89.0 min (p = 0.0001) and −39.8 min (p = 0.0165) for OPC-50 mg patients with and without CPU. There was ~45% more OFF-time reduction in PLC patients without CPU than in those with, but ~20% less OFF-time reduction in OPC-50 mg patients without CPU than in those with. A higher-than-PLC proportion of OPC-50 mg-receiving patients with CPU achieved OFF- (72.9% vs. 40.4%; p < 0.0001) and ON-time (68.8% vs. 42.6%; p = 0.0003) responders’ endpoint. Consistently, a higher-than-PLC proportion of OPC-50 mg-receiving patients without CPU achieved OFF- (64.5% vs. 54.0%; p = 0.0551) and ON-time (60.2% vs. 47.2%; p = 0.0169) responders’ endpoint. Opicapone was effective regardless of concurrent pramipexole use.

Opicapone for the treatment of Parkinson's disease: A review of a new licensed medicine.

Catechol-O-methyl transferase inhibitors are currently used as first-line add-on therapy to levodopa for the treatment of end-of-dose motor fluctuations in Parkinson's disease patients, as they increase levodopa bioavailability. Several factors hamper the use of current available catechol-O-methyl transferase inhibitors, that is, the moderate efficacy and multiple dosing for entacapone and the risk of liver toxicity with tolcapone. Opicapone, a new long-acting, peripherally selective, once-daily catechol-O-methyl transferase inhibitor, was recently licensed in Europe. Two phase 3 double-blind clinical trials demonstrated opicapone efficacy in reducing OFF time by an average of about 60 minutes daily compared with placebo, without increasing ON time with troublesome dyskinesias. These effects were also maintained during a subsequent open-label extension consisting of 1-year follow-up. Opicapone showed a good safety profile. From June 2016, Opicapone received the approval for marketing authorization from the European Commission as adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in patients with PD and end-of-dose motor fluctuations. We aimed to review the clinical pharmacological data of opicapone, summarize its clinical efficacy and safety issues, and discuss its potential role in the management of Parkinson's disease. © 2018 International Parkinson and Movement Disorder Society.

Opicapone as an adjunct to levodopa in patients with Parkinson's disease and end-of-dose motor fluctuations: a randomised, double-blind, controlled trial

Opicapone is a novel, once-daily, potent third-generation catechol-O-methyltransferase inhibitor. We aimed to assess the safety and efficacy of opicapone as an adjunct to levodopa compared with placebo or entacapone in patients with Parkinson's disease and motor fluctuations. We did a randomised, double-blind, placebo-controlled and active-controlled trial of opicapone as an adjunct to levodopa in patients with Parkinson's disease with end-of-dose motor fluctuations. Patients aged 30-83 years were enrolled at 106 specialist centres across 19 European countries and Russia and were randomly assigned (1:1:1:1:1) by a proprietary computer-generated sequence to oral treatment with opicapone (5 mg, 25 mg, or 50 mg once daily), placebo, or entacapone (200 mg with every levodopa intake) for 14-15 weeks. Patients and investigators (ie, outcome assessors) were masked to treatment allocation. The primary endpoint was the change from baseline to end of study treatment in absolute time in the off state, as assessed by daily paper patient diaries; the primary analysis followed a hierarchical procedure for each opicapone dose in which superiority compared with placebo in the full analysis set was first tested and then, if positive, non-inferiority to entacapone was tested in the per-protocol set with a margin of 30 min. This trial is registered with EudraCT, 2010-021860-13, and ClinicalTrials.gov, NCT01568073. Between March 31, 2011, and Nov 30, 2013, of 679 patients screened, 600 were randomly assigned. 590 patients were included in the full analysis set (120 in the placebo group, 120 in the entacapone group, 119 in the opicapone 5 mg group, 116 in the opicapone 25 mg group, and 115 in the opicapone 50 mg group) and 537 in the per-protocol set (112 in the placebo group, 104 in the entacapone group, 110 in the opicapone 5 mg group, 105 in the opicapone 25 mg group, and 106 in the opicapone 50 mg group). The mean change in time in the off state was -56·0 min (SE 13·4; 95% CI -82·3 to -29·7) for placebo, -96·3 min (13·4; -122·6 to -70·0) for entacapone, -91·3 min (13·5; -117·7 to -64·8) for opicapone 5 mg, -85·9 min (13·7; -112·8 to -59·1) for opicapone 25 mg, and -116·8 min (14·0; -144·2 to -89·4) for opicapone 50 mg. Treatment with opicapone 50 mg was superior to placebo (mean difference in change from baseline -60·8 min, 95% CI -97·2 to -24·4; p=0·0015) and non-inferior to entacapone (-26·2 min, -63·8 to 11·4; p=0·0051). Treatment with opicapone 5 mg (p=0·056) or 25 mg (p=0·080) was not significantly different from treatment with placebo. Treatment-emergent adverse events were reported in 60 (50%) of 121 patients in the placebo group, 69 (57%) of 122 in the entacapone group, 63 (52%) of 122 in the opicapone 5 mg group, 65 (55%) of 119 in the opicapone 25 mg group, and 62 (54%) of 115 in the opicapone 50 mg group. The most common adverse events were dyskinesia (in five patients in the placebo group, ten in the entacapone group, 17 in the opicapone 5 mg group, nine in the opicapone 25 mg group, and 18 in the opicapone 50 mg group), insomnia (in one, seven, two, seven, and seven patients, respectively), and constipation (in three, five, four, none, and seven patients, respectively). Serious adverse events were reported in six patients in the placebo group, eight in the entacapone group, four each in the opicapone 5 mg and opicapone 50 mg groups, and one in the opicapone 25 mg group. The addition of opicapone 50 mg to levodopa treatment in patients with Parkinson's disease and end-of-dose motor fluctuations could enable a simplified drug regimen that allows physicians to individually tailor the existing levodopa daily regimen, by potentially reducing the total daily levodopa dose, increasing the dosing interval, and ultimately reducing the number of intakes, thereby maximising its benefit. BIAL.

One-year follow-up of opicapone's efficacy and safety in patients with Parkinson’s disease and motor fluctuations (BIPARK I)

One-year follow-up of opicapone's efficacy and safety in patients with Parkinson’s disease and motor fluctuations (BIPARK I)

Pooled efficacy of opicapone as adjunctive therapy to levodopa in patients with Parkinson’s disease and motor fluctuations

Pooled efficacy of opicapone as adjunctive therapy to levodopa in patients with Parkinson’s disease and motor fluctuations